CINXE.COM
Parkinson’s Disease Associated With Neuroinflammation in the Brain, New Analyses Reveal < Yale Center for Clinical Investigation
<!DOCTYPE html> <html lang="en"> <head itemscope itemtype="http://schema.org/SpeakableSpecification"> <!-- Google Tag Manager --> <script> window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('consent', 'default', { 'ad_storage': 'denied', 'analytics_storage': 'denied' }); gtag('set', 'ads_data_redaction', true); </script> <script>(function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start': new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0], j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src= 'https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f); })(window,document,'script','dataLayer','GTM-T29B2V8');</script> <!-- End Google Tag Manager --> <meta charset="utf-8"/> <meta name="viewport" content="width=device-width, initial-scale=1.0"/> <meta http-equiv="X-UA-Compatible" content="IE=EDGE"/> <title>Parkinson’s Disease Associated With Neuroinflammation in the Brain, New Analyses Reveal < Yale Center for Clinical Investigation</title> <link rel="preconnect" href="https://p.typekit.net"> <link rel="dns-prefetch" href="https://p.typekit.net"> <link rel="preconnect" href="https://use.typekit.net"> <link rel="dns-prefetch" href="https://use.typekit.net"> <link rel="preconnect" href="https://www.gstatic.com"> <link rel="dns-prefetch" href="https://www.gstatic.com"> <meta name="title" property="og:title" content="Parkinson’s Disease Associated With Neuroinflammation in the Brain, New Analyses Reveal " /> <meta itemprop="xpath" content="/html/head/meta[@property='og:title']/@content" /> <meta name="description" property="og:description" content="Using single-cell transcriptomics and proteomics, Yale researchers have created a detailed cell atlas of brains affected by Parkinson’s disease." /> <meta itemprop="xpath" content="/html/head/meta[@name='description']/@content" /> <meta name="robots" content="noindex, nofollow"> <meta property="author" content="Isabella Backman" /> <meta property="publish-date" content="11/07/2024" /> <meta property="og:url" content="https://medicine.yale.edu/center-clinical-investigation/news-article/parkinsons-disease-associated-with-neuroinflammation-in-the-brain-new-analyses-reveal/" /> <meta name="site-name" property="og:site_name" content="Yale Center for Clinical Investigation" /> <meta property="og:type" content="article" /> <meta property="og:title" content="Parkinson’s Disease Associated With Neuroinflammation in the Brain, New Analyses Reveal " /> <meta property="og:description" content="Using single-cell transcriptomics and proteomics, Yale researchers have created a detailed cell atlas of brains affected by Parkinson’s disease." /> <meta name="twitter:card" content="summary" /> <meta name="twitter:image:alt" content="GettyImages-117099409040" /> <meta property="og:image" content="https://ysm-res.cloudinary.com/image/upload/c_limit,f_auto,h_630,q_auto,w_1200/v1/yms/prod/91883f7d-73a9-41a4-9ea4-9ddb22f7d5bc" /> <meta property="og:image:secure_url" content="https://ysm-res.cloudinary.com/image/upload/c_limit,f_auto,h_630,q_auto,w_1200/v1/yms/prod/91883f7d-73a9-41a4-9ea4-9ddb22f7d5bc" /> <meta property="og:image:width" content="1200" /> <meta property="og:image:height" content="630" /> <meta property="fb:app_id" content="604142276782606" /> <link rel="canonical" href="https://medicine.yale.edu/news-article/parkinsons-disease-associated-with-neuroinflammation-in-the-brain-new-analyses-reveal/"> <link rel="apple-touch-icon" sizes="180x180" href="https://cdn1.medicine.yale.edu/icons/ysm/apple-touch-icon.png"> <link rel="icon" type="image/png" href="https://cdn1.medicine.yale.edu/icons/ysm/favicon-32x32.png" sizes="32x32"> <link rel="icon" type="image/png" href="https://cdn1.medicine.yale.edu/icons/ysm/favicon-16x16.png" sizes="16x16"> <link rel="manifest" href="https://cdn1.medicine.yale.edu/web-manifests/ysm/site.webmanifest"> <link rel="shortcut icon" type="image/x-icon" href="https://cdn1.medicine.yale.edu/icons/ysm/favicon.ico"/> <meta name="msapplication-TileColor" content="#1271e3"> <meta name="msapplication-config" content="https://cdn1.medicine.yale.edu/browser-configs/ysm/browserconfig.xml"> <meta name="theme-color" content="#ffffff"> <link rel="preload" href="https://cdn1.medicine.yale.edu/build/yalenew-italic-webfront.woff2" as="font" crossorigin> <link rel="preload" href="https://cdn1.medicine.yale.edu/build/yalenew-roman-webfont.woff2" as="font" crossorigin> <link rel="preload" href="https://use.typekit.net/eqf4dwf.css" as="style" crossorigin> <link data-chunk="main" rel="stylesheet" href="https://cdn1.medicine.yale.edu/build/main.2219cf4e0ca2819d1aa4.css" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-NewsDetails" rel="stylesheet" href="https://cdn1.medicine.yale.edu/build/3688.fd25f5ff6219387f8dc4.css" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-NewsDetails" rel="stylesheet" href="https://cdn1.medicine.yale.edu/build/1578.a215639acfdf115abdc4.css" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-NewsDetails" rel="stylesheet" href="https://cdn1.medicine.yale.edu/build/186.9f3ceeb7736a80bc849d.css" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-news-details-sidebar-NewsDetailsSidebar" rel="stylesheet" href="https://cdn1.medicine.yale.edu/build/4480.b2fbb0bf4690d5a2f302.css" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-news-details-sidebar-NewsDetailsSidebar" rel="stylesheet" href="https://cdn1.medicine.yale.edu/build/6391.ee335c8ce6e72b09ba55.css" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-news-details-sidebar-NewsDetailsSidebar" rel="stylesheet" href="https://cdn1.medicine.yale.edu/build/5504.69c0d610677e53ceb377.css" crossorigin="anonymous" /> <link data-chunk="modules-footer-components-Footer" rel="stylesheet" href="https://cdn1.medicine.yale.edu/build/3053.6076590112c5b82bb4a4.css" crossorigin="anonymous" /> <link data-chunk="modules-footer-components-Footer" rel="preload" as="style" href="https://cdn1.medicine.yale.edu/build/3053.6076590112c5b82bb4a4.css" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-news-details-sidebar-NewsDetailsSidebar" rel="preload" as="style" href="https://cdn1.medicine.yale.edu/build/5504.69c0d610677e53ceb377.css" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-news-details-sidebar-NewsDetailsSidebar" rel="preload" as="style" href="https://cdn1.medicine.yale.edu/build/6391.ee335c8ce6e72b09ba55.css" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-news-details-sidebar-NewsDetailsSidebar" rel="preload" as="style" href="https://cdn1.medicine.yale.edu/build/4480.b2fbb0bf4690d5a2f302.css" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-NewsDetails" rel="preload" as="style" href="https://cdn1.medicine.yale.edu/build/186.9f3ceeb7736a80bc849d.css" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-NewsDetails" rel="preload" as="style" href="https://cdn1.medicine.yale.edu/build/1578.a215639acfdf115abdc4.css" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-NewsDetails" rel="preload" as="style" href="https://cdn1.medicine.yale.edu/build/3688.fd25f5ff6219387f8dc4.css" crossorigin="anonymous" /> <link data-chunk="main" rel="preload" as="style" href="https://cdn1.medicine.yale.edu/build/main.2219cf4e0ca2819d1aa4.css" crossorigin="anonymous" /> <link data-chunk="main" rel="preload" as="script" href="https://cdn1.medicine.yale.edu/build/main.es2015.ff4738d7fae8cd594b64.js" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-NewsDetails" rel="preload" as="script" href="https://cdn1.medicine.yale.edu/build/4589.es2015.4c47bf8350b6c4f009a0.js" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-NewsDetails" rel="preload" as="script" href="https://cdn1.medicine.yale.edu/build/7640.es2015.305f7f9c55b908f8d7a2.js" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-NewsDetails" rel="preload" as="script" href="https://cdn1.medicine.yale.edu/build/3688.es2015.61379309f5274f4b1158.js" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-NewsDetails" rel="preload" as="script" href="https://cdn1.medicine.yale.edu/build/7651.es2015.df8b8aeaf41f78f2ec07.js" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-NewsDetails" rel="preload" as="script" href="https://cdn1.medicine.yale.edu/build/1578.es2015.dd71c3003a75394cf84a.js" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-NewsDetails" rel="preload" as="script" href="https://cdn1.medicine.yale.edu/build/186.es2015.18f4db14c8e5e4065c1f.js" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-news-details-sidebar-NewsDetailsSidebar" rel="preload" as="script" href="https://cdn1.medicine.yale.edu/build/6443.es2015.4890cbc400a8796edee4.js" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-news-details-sidebar-NewsDetailsSidebar" rel="preload" as="script" href="https://cdn1.medicine.yale.edu/build/4480.es2015.473ffd08eabb889a822c.js" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-news-details-sidebar-NewsDetailsSidebar" rel="preload" as="script" href="https://cdn1.medicine.yale.edu/build/6736.es2015.36fcc1e83004e7c6188d.js" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-news-details-sidebar-NewsDetailsSidebar" rel="preload" as="script" href="https://cdn1.medicine.yale.edu/build/9819.es2015.0646cda325bf5675c53b.js" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-news-details-sidebar-NewsDetailsSidebar" rel="preload" as="script" href="https://cdn1.medicine.yale.edu/build/6391.es2015.97db24b9904b8087c7f2.js" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-news-details-sidebar-NewsDetailsSidebar" rel="preload" as="script" href="https://cdn1.medicine.yale.edu/build/1739.es2015.57164941c596da5ad19e.js" crossorigin="anonymous" /> <link data-chunk="modules-article-components-news-news-details-sidebar-NewsDetailsSidebar" rel="preload" as="script" href="https://cdn1.medicine.yale.edu/build/5504.es2015.92e50a2dd82c1109ec41.js" crossorigin="anonymous" /> <link data-chunk="modules-footer-components-Footer" rel="preload" as="script" href="https://cdn1.medicine.yale.edu/build/3053.es2015.359573b73638d4069b34.js" crossorigin="anonymous" /> <script data-schema="Article" type="application/ld+json"> {"@type":"Article","inLanguage":"en-US","mainEntityOfPage":{"@type":"WebPage","@id":"https://medicine.yale.edu/news-article/parkinsons-disease-associated-with-neuroinflammation-in-the-brain-new-analyses-reveal/","@context":"http://schema.org"},"headline":"Parkinson’s Disease Associated With Neuroinflammation in the Brain, New Analyses Reveal ","url":"https://medicine.yale.edu/news-article/parkinsons-disease-associated-with-neuroinflammation-in-the-brain-new-analyses-reveal/","Image":{"@type":"ImageObject","url":"https://ysm-res.cloudinary.com/image/upload/c_limit,f_auto,h_630,q_auto,w_1200/v1/yms/prod/91883f7d-73a9-41a4-9ea4-9ddb22f7d5bc","description":"GettyImages-117099409040","height":1200,"width":630,"@context":"http://schema.org"},"dateCreated":"2024-11-07","datePublished":"2024-11-07","articleBody":"Using groundbreaking emerging sequencing technologies, Yale School of Medicine scientists are studying human brains impacted by Parkinson’s disease in unprecedented detail. This research is bringing them closer to understanding how the life-altering condition arises. In a recent study, the researchers generated a cell atlas—a comprehensive reference that maps out all cell types within an organ—based on postmortem human brains from individuals with late-stage disease. Using single cell transcriptomics and proteomics, which enabled them to measure gene and protein expression, they compared how their findings differed from that found in healthy controls. Their findings revealed key differences, including that brains affected by Parkinson’s disease have greater levels of neuroinflammation. The researchers also compared their Parkinson’s cell atlas to a previously published one that mapped cell types found in human brains affected by Alzheimer’s disease. They found that each disease has a distinct pathology that impacts the neurons differently but common signatures in glial cells and neuroinflammation. The researchers published their findings in Science Translational Medicine on October 30. The research was led by Le Zhang, PhD, assistant professor of neurology and of neuroscience, Sreeganga Chandra, PhD, associate professor of neurology and neuroscience, and David Hafler, MD, the William S. and Lois Stiles Edgerly Professor of Neurology and professor of immunobiology at Yale. “What we really want to do is learn how to prevent Parkinson’s disease,” says Hafler, who is also chair of Yale’s Department of Neurology. “This work in the brain is one more piece of the puzzle that suggests the importance of inflammation as a cause of the disease.” Parkinson’s disease is a progressive neurodegenerative disorder that impacts millions of people around the world. The condition is characterized by loss of neurons in the substantia nigra, a region in the midbrain that produces dopamine. It is also associated with the formation of Lewy bodies—abnormal clumps of protein that develop inside nerve cells in the brain. While Parkinson’s disease is primarily known for motor symptoms that result from the degeneration of dopamine-producing neurons, it also causes prefrontal cortex dysfunction. The prefrontal cortex is the region of the brain associated with complex cognitive functions such as decision-making, attention, and working memory. This region is also significantly impacted by Alzheimer’s disease. Parkinson’s disease is linked to greater levels of neuroinflammation Researchers have not had much insight into the underlying pathways that contribute to the onset and progression of Parkinson’s disease. Now, in their latest study, the Yale-led team ran multiple analyses on post-mortem tissue. By focusing their investigation on the prefrontal cortex, they were able to compare their analyses to previously reported data on Alzheimer’s disease. The team ran two major analyses: single-cell transcriptomics and proteomics. Through single-cell transcriptomics, they isolated the nuclei of the brain cells in the prefrontal cortex and sequenced all of the RNA, known as “the transcriptome.” Then, they compared differences in gene expression found in brains with Parkinson’s disease against healthy controls. Using the same tissue, they also ran a proteomics analysis, in which they used an analytical technique called mass spectrometry to measure protein expression in the tissues. This enabled the researchers to understand how the expression of proteins differs in Parkinson’s disease. “Our study helped us understand the gene changes in Parkinson’s disease at the cell type level,” says Zhang. “By integrating this with our proteomics data, we can better understand the effects of the disease at both RNA and protein levels.” The researchers found that brains with Parkinson’s disease showed signs of increased neuroinflammation, including elevated levels of two kinds of immune cells known as T cells and microglia. Furthermore, they found that the presence of Lewy bodies was inversely correlated to the expression of a class of proteins called chaperones—these enable other proteins to fold properly and prevent them from aggregating—in excitatory neurons that regulate electrical signals in the brain. This finding could have therapeutic implications, the authors say. “If we could increase chaperone capacity in the brain, we could potentially decrease the abnormal aggregation associated with Parkinson’s,” says Chandra. Next, the team looked for shared features between brains with Parkinson’s disease and Alzheimer’s disease. “We wanted to compare the two most common neurodegenerative diseases,” explains Zhang. To their surprise, they did not find any overlap in gene expression within neurons. This suggests that the diseases likely impact neurons in distinct ways, the researchers say. “Parkinson’s and Alzheimer’s are clinically different diseases that have different mechanisms, and therefore the options to treat them will be different,” says Chandra. Cell atlas will help guide future research The study gave researchers important insight into how Parkinson’s disease arises. “Before the advent of these technologies, we couldn’t interrogate human tissue to get insights into disease progression,” says Chandra. “These analyses will help inform our future experiments and are a platform to raise pertinent questions that we can test.” The team hopes their cell atlas will help guide the studies of research teams investigating Parkinson’s disease. In their own labs, the researchers’ next steps are to apply the same methods to brains in the early stages of the condition. In addition, they are looking at the blood and spinal fluid of patients, where they have also found signs of inflammation. Based on insights from these studies, the researchers plan to conduct clinical trials aimed at preventing the disease.","author":[{"@type":"Person","name":"Isabella Backman","@context":"http://schema.org"}],"keywords":[],"publisher":{"@type":"NewsMediaOrganization","name":"Yale School of Medicine","foundingDate":"1810-10-15","duns":"003036709","url":"https://medicine.yale.edu","logo":{"@type":"ImageObject","url":"https://medicine.yale.edu/icons/ysm/largetile.png","height":310,"width":310,"@context":"http://schema.org"},"sameAs":["https://www.facebook.com/YaleSchoolOfMedicine","https://twitter.com/YaleMed","https://www.instagram.com/yaleschoolofmed/?hl=en","https://www.linkedin.com/school/yale-university-school-of-medicine/","https://www.youtube.com/user/YaleMedicine","https://vimeo.com/user30675202"],"department":"Office of Communication","parentOrganization":{"@type":"CollegeOrUniversity","Name":"Yale University","foundingDate":"1701","duns":"043207562","url":"https://www.yale.edu/","address":{"@type":"PostalAddress","addressCountry":"USA","addressLocality":"New Haven","addressRegion":"CT","postalCode":"06520","streetAddress":"333 Cedar Street","@context":"http://schema.org"},"@context":"http://schema.org"},"@context":"http://schema.org"},"@context":"http://schema.org"} </script> <script type="text/javascript"> (function (c, a) { if (!a.__SV) { var b = window; try { var d, m, j, k = b.location, f = k.hash; d = function (a, b) { return (m = a.match(RegExp(b + "=([^&]*)"))) ? m[1] : null }; f && d(f, "fpState") && (j = JSON.parse(decodeURIComponent(d(f, "fpState"))), "fpeditor" === j.action && (b.sessionStorage.setItem("_fpcehash", f), history.replaceState(j.desiredHash || "", c.title, k.pathname + k.search))) } catch (n) { } var l, h; window.freshpaint = a; a._i = []; a.init = function (b, d, g) { function c(b, i) { var a = i.split("."); 2 == a.length && (b = b[a[0]], i = a[1]); b[i] = function () { b.push([i].concat(Array.prototype.slice.call(arguments, 0))) } } var e = a; "undefined" !== typeof g ? e = a[g] = [] : g = "freshpaint"; e.people = e.people || []; e.toString = function (b) { var a = "freshpaint"; "freshpaint" !== g && (a += "." + g); b || (a += " (stub)"); return a }; e.people.toString = function () { return e.toString(1) + ".people (stub)" }; l = "disable time_event track track_pageview track_links track_forms track_with_groups add_group set_group remove_group register register_once alias unregister identify name_tag set_config reset opt_in_tracking opt_out_tracking has_opted_in_tracking has_opted_out_tracking clear_opt_in_out_tracking people.set people.set_once people.unset people.increment people.append people.union people.track_charge people.clear_charges people.delete_user people.remove people group page alias ready addEventProperties addInitialEventProperties removeEventProperty addPageviewProperties".split(" "); for (h = 0; h < l.length; h++)c(e, l[h]); var f = "set set_once union unset remove delete".split(" "); e.get_group = function () { function a(c) { b[c] = function () { call2_args = arguments; call2 = [c].concat(Array.prototype.slice.call(call2_args, 0)); e.push([d, call2]) } } for (var b = {}, d = ["get_group"].concat(Array.prototype.slice.call(arguments, 0)), c = 0; c < f.length; c++)a(f[c]); return b }; a._i.push([b, d, g]) }; a.__SV = 1.4; b = c.createElement("script"); b.type = "text/javascript"; b.async = !0; b.src = "undefined" !== typeof FRESHPAINT_CUSTOM_LIB_URL ? FRESHPAINT_CUSTOM_LIB_URL : "//perfalytics.com/static/js/freshpaint.js"; (d = c.getElementsByTagName("script")[0]) ? d.parentNode.insertBefore(b, d) : c.head.appendChild(b) } })(document, window.freshpaint || []); freshpaint.init("b6b4bb12-e8a3-48f7-a8ed-aa0be94fb272"); freshpaint.page(); </script> <script type="text/plain" data-cookiecategory="analytics"> (function (c, l, a, r, i, t, y) { c[a] = c[a] || function () { (c[a].q = c[a].q || []).push(arguments) }; t = l.createElement(r); t.async = 1; t.src = "https://www.clarity.ms/tag/" + i; y = l.getElementsByTagName(r)[0]; y.parentNode.insertBefore(t, y); })(window, document, "clarity", "script", "h8jhq78c9x"); </script> <script id="cms-page-metadata" type="text/template"> ********************************************** CMS Page ID: 13824 Last Published: 09/17/2024 11:43:57 ********************************************** </script> </head> <body tabindex="-1"> <!-- Google Tag Manager (noscript) --> <noscript aria-hidden="true"> <iframe src="https://www.googletagmanager.com/ns.html?id=GTM-T29B2V8" height="0" width="0" style="display: none; visibility: hidden"></iframe> </noscript> <!-- End Google Tag Manager (noscript) --> <!--[if IE]> <div aria-hidden="true" class="outdated-browser-warning"> Your browser is antiquated and no longer supported on this website. Please update your browser or switch to Chrome, Firefox or Safari. <br/> You can update your IE here: <br/> <a class="outdated-browser-warning__link" href="https://support.microsoft.com/en-us/help/17621/internet-explorer-downloads">https://support.microsoft.com/en-us/help/17621/internet-explorer-downloads</a> </div> <![endif]--> <!--[if !IE]>--> <div id="app"><div class="page"><span role="navigation" aria-label="Skip to Main Content button"><a href="#page-container" class="skip-button skip-button--dark skip-to-main-content-button">Skip to Main Content</a></span><div class="base-page__header-container"><div class="base-header department-header"><div class="base-header__content"><div class="base-header__top-navigation-container"><div class="base-header__top-navigation"><nav class="base-header__top-navigation-links" aria-label="Information links"><a href="/" class="department-header__top-navigation-root-link"><svg xmlns="http://www.w3.org/2000/svg" aria-label="Yale School of Medicine" viewBox="0 0 384.2 29.1" focusable="false" class="site-wordmark__icon site-wordmark__icon--mode-ysm department-header__logo-icon"><desc>Yale School of Medicine</desc><path d="m22.3 6.1-6.8 11.5v7.7c.8 1.9 2.8 2.1 4.7 2.2v1.1H6.8v-1.1c1.9-.1 4.2-.4 4.8-1.6v-8l-7-11.8C3.5 4.2 2.3 3.5 0 3.4V2.3h11.6v1.1c-2.2.1-2.9.5-3.5 1l6.5 11.2 6.3-11.1c-.7-.5-1.5-1-3.7-1.1V2.3h9.9v1.1c-2.2 0-3.6.8-4.8 2.7M35.9 29c-2.2 0-3.3-1.5-3.4-2.6-1.4 1.5-3.2 2.6-5 2.6-2.2 0-4.1-1.4-4.1-3.7 0-1.2.3-2.4.9-3.3l8.2-3v-3.1c0-1.9-.9-3.6-2.7-3.6-1.1 0-2.2 1.4-2.3 3.5l-3.7.6V16c1.2-3.7 5.3-5.2 7.3-5.2 3.8 0 5.1 2 5.1 5.1l-.1 8.7c0 1.7.9 2.1 1.7 2.1.7 0 1.3-.4 2.1-1.2v1.2c-.9 1-2.5 2.3-4 2.3m-8.3-6.8c-.2.7-.3 1.2-.3 2.2 0 1.2.7 2.5 2.1 2.5 1.2 0 1.9-.4 3.1-1.3V20c-1.1.5-3.7 1.7-4.9 2.2m12.7 6.4v-1c1.9-.1 2.4-.5 2.7-1.2V5c0-1.4-.2-2-3.1-2.2v-.9L47.5 0l.2.7-1.2 1.5v24.2c.4.8 1.2 1.1 2.9 1.2v1zm19.1.4c-4.3 0-7.7-3.4-7.7-8.2 0-5.9 3.6-9.9 8.7-9.9 4.1 0 6.4 2.3 6.4 6v.7l-11.2-.1c-.1.5-.1 1.2-.1 2.1 0 4.2 2.7 7 6.2 7 2.1 0 3.2-.7 4.8-2.2l.6 1c-2.4 2.1-4.3 3.6-7.7 3.6m.4-16.9c-2.1 0-3.5 1.7-4 4.3l7.3-.1c-.1-2.2-1.4-4.2-3.3-4.2M83.4 29.1c-2.1 0-3.8-.6-4.9-1l-.5-4.4h.7c.2 1.1 1 2.5 2 3.2.6.5 1.9 1.2 3 1.2 2.2 0 3.3-1.4 3.3-2.8 0-1.9-1.2-2.4-3.2-3.2-3.8-1.6-5.2-2.6-5.2-5.2 0-2.9 2.9-4.8 6.7-4.8 1.8 0 3.2.5 4.1.9v4.3h-.7c-.1-1.1-.5-2.5-1.5-3.1-.4-.2-1.4-.9-2.6-.9-2.1 0-3.2 1.3-3.2 2.6 0 1.7.9 2.4 3.5 3.4 3.5 1.4 5 2.5 5 5 0 2.9-2.9 4.8-6.5 4.8m25.1-1c-2 .6-2.6.9-5.7.9-5.3 0-9.2-3.8-9.2-8.7 0-5 4.1-8.4 9.2-8.4 2.6 0 4 .5 5.9.9v4.5h-.7c-.1-1.1-.6-2.4-1.5-3-.5-.3-1.7-1.3-3.9-1.3-3.7 0-5.8 3.1-5.8 6.7 0 4.8 2.7 8.2 7 8.2 1.4 0 2.4-.6 2.8-.9 1-.8 1.7-2 2-3.2l.8.1zm15.4.6V28c1.2 0 2.2-.4 2.5-.9V21h-8.8v6.1c.2.5 1.3.8 2.5.9v.7h-7.8V28c1.1 0 2.3-.4 2.5-.9V13.9c-.2-.5-1.3-.8-2.5-.9v-.7h7.8v.7c-1.1.1-2.3.4-2.5.9v5.7h8.8v-5.7c-.3-.5-1.3-.8-2.5-.9v-.7h7.9v.7c-1.2.1-2.2.4-2.5.9v13.2c.3.5 1.3.8 2.5.9v.7zm18.9.4c-5.2 0-8.2-3.6-8.2-8.5 0-5 4.2-8.6 9.3-8.6 5.3 0 8.2 3.6 8.2 8.4 0 5.1-4.1 8.7-9.3 8.7m-.3-16c-2.4 0-4.8 2.7-4.8 6.7 0 4.7 2.3 8.1 6.3 8.1 2.6 0 5-2.6 5-6.7 0-4.9-2.5-8.1-6.5-8.1m21.4 16c-5.2 0-8.2-3.6-8.2-8.5 0-5 4.2-8.6 9.3-8.6 5.3 0 8.2 3.6 8.2 8.4 0 5.1-4.1 8.7-9.3 8.7m-.3-16c-2.4 0-4.8 2.7-4.8 6.7 0 4.7 2.3 8.1 6.3 8.1 2.6 0 5-2.6 5-6.7 0-4.9-2.5-8.1-6.5-8.1m11.9 15.6V28c1-.1 2.6-.3 3-1.2V13.9c-.2-.5-1.3-.8-2.5-.9v-.7h8.1v.7c-1.1.1-2.5.4-2.7.9v13.5l4.7-.1c1.8 0 2.9-1.7 2.9-3.9h.7v5.3zm33 .4c-5.2 0-8.2-3.6-8.2-8.5 0-5 4.2-8.6 9.3-8.6 5.3 0 8.2 3.6 8.2 8.4.1 5.1-4.1 8.7-9.3 8.7m-.3-16c-2.4 0-4.8 2.7-4.8 6.7 0 4.7 2.3 8.1 6.3 8.1 2.6 0 5-2.6 5-6.7 0-4.9-2.5-8.1-6.5-8.1m24.4 3.4c-.1-2.3-1-2.9-3-2.9H226V20l3.5-.1c1.7-.1 2.4-.1 2.7-2h.7v5.5h-.7c-.2-2.1-.9-2.1-2.6-2.1h-3.5v5.5c.3.8 1.8 1.2 3 1.3v.7h-8.6V28c1.1-.1 2.4-.3 2.7-1.1V14c-.2-.6-1.4-.9-2.6-.9v-.7h10.7c.6 0 1.1 0 1.5-.2h.6v4.3zm26.2 12.2V28c1.2-.1 2.5-.4 2.7-.9l-.5-9.5v-2.7l-.8 2.1-5.2 11.7h-1l-4.5-12.3-.7-2-.1 1.8-.7 10.6c.2.5 1.4 1 2.6 1.1v.7h-6.7V28c1.2-.1 2.3-.6 2.6-1.1l.7-9.2c.1-.9.2-2.8.2-2.9V14c-.3-.4-1.1-.8-2.3-.9v-.7h5.8l.8 2.5 3.7 10.2 4.2-9.9 1.1-2.7h5.2v.5c-1.2.1-2.1.4-2.3.8v.6c0 .3.1 2.3.2 3.1l.5 9.5c.3.5 1.4.8 2.5.9v.7h-8zm16.5 0-5.8.1v-.7c1.2-.1 2.9-.4 3.3-1.2v-13c-.2-.5-1.3-.8-2.5-.9v-.7H281c.7 0 1.2-.1 1.5-.2h.6v4.3h-.7c-.1-2.3-1-2.9-3-2.9h-3.7v6.1h3.5c1.8 0 2.5 0 2.7-1.9h.6V23h-.7c-.2-2.1-.8-2.1-2.7-2.1h-3.5v5.6c.1.3.2.7.7.9l4.1-.1c1.7 0 2.9-.8 2.9-3h.6v4.3h-8.6zm20.8 0h-8.6V28c1.1 0 2.4-.4 2.6-.9V13.9c-.2-.5-1.5-.8-2.7-.9v-.7c3-.1 5.9-.3 8.2-.3 5.9 0 9.4 3 9.4 8s-3.9 8.8-8.9 8.7M294.5 13H293v13.9c.3.4 1.7.8 2.7.8 4.1 0 6.1-2.8 6.1-6.8 0-5.3-2.8-7.9-7.3-7.9m13.1 15.7V28c1.2-.1 2.4-.4 2.6-.9V13.9c-.2-.5-1.4-.8-2.6-.9v-.7h8.2v.7c-1.2.1-2.4.4-2.6.9V27c.2.5 1.4.8 2.6.9v.7h-8.2zm25.6-.6c-2 .6-2.6.9-5.7.9-5.3 0-9.2-3.8-9.2-8.7 0-5 4.1-8.4 9.2-8.4 2.6 0 4 .5 5.9.9v4.5h-.7c-.1-1.1-.6-2.4-1.5-3-.5-.3-1.7-1.3-3.9-1.3-3.7 0-5.8 3.1-5.8 6.7 0 4.8 2.7 8.2 7 8.2 1.4 0 2.4-.6 2.8-.9 1-.8 1.7-2 2-3.2l.8.1zm3.8.6V28c1.2-.1 2.4-.4 2.6-.9V13.9c-.2-.5-1.4-.8-2.6-.9v-.7h8.2v.7c-1.2.1-2.4.4-2.6.9V27c.2.5 1.4.8 2.6.9v.7H337zm27.8-14.5V24c0 1.4.1 3.7.2 4.9h-1.6l-10-12.3-1.1-1.7.1 1.5v5.9c0 1.4.1 3.4.2 4.5.2.5 1.7 1 2.9 1.1v.7h-7.1V28c1.2-.1 2.3-.6 2.5-1.1v-9.2c0-1.3 0-2.6-.1-3.5-.3-.5-1.3-1-2.5-1.1v-.7h5.2l1.5 1.9 8.4 10.3v-5.9c0-1.4-.1-3.6-.1-4.4-.2-.5-1.7-1.1-2.9-1.1v-.7h7.1v.5c-1.3.1-2.4.6-2.7 1.2m10.7 14.5-5.8.1v-.7c1.2-.1 2.9-.4 3.3-1.2v-13c-.2-.5-1.3-.8-2.5-.9v-.7h10.7c.7 0 1.2-.1 1.5-.2h.6v4.3h-.7c-.1-2.3-1-2.9-3-2.9h-3.7v6.1h3.5c1.8 0 2.5 0 2.7-1.9h.6V23h-.7c-.2-2.1-.8-2.1-2.7-2.1h-3.5v5.6c.1.3.2.7.7.9l4.1-.1c1.7 0 2.9-.8 2.9-3h.6v4.3h-8.6z"></path></svg></a><div class="navigation-header-links"><a href="/about/" class="navigation-header-links__header-link" aria-label="Navigate to About YSM page"><div class="navigation-header-links__link-hover"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-header-links__link-icon"><path fill="none" d="M0 0h24v24H0z"></path><path d="m12 4-1.41 1.41L16.17 11H4v2h12.17l-5.58 5.59L12 20l8-8z"></path></svg>About YSM</div></a><a href="/faculty/" class="navigation-header-links__header-link" aria-label="Navigate to Faculty page"><div class="navigation-header-links__link-hover"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-header-links__link-icon"><path fill="none" d="M0 0h24v24H0z"></path><path d="m12 4-1.41 1.41L16.17 11H4v2h12.17l-5.58 5.59L12 20l8-8z"></path></svg>Faculty</div></a><a href="/myysm/" class="navigation-header-links__header-link" aria-label="Navigate to Staff page"><div class="navigation-header-links__link-hover"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-header-links__link-icon"><path fill="none" d="M0 0h24v24H0z"></path><path d="m12 4-1.41 1.41L16.17 11H4v2h12.17l-5.58 5.59L12 20l8-8z"></path></svg>Staff</div></a><a href="/edu/" class="navigation-header-links__header-link" aria-label="Navigate to Students page"><div class="navigation-header-links__link-hover"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-header-links__link-icon"><path fill="none" d="M0 0h24v24H0z"></path><path d="m12 4-1.41 1.41L16.17 11H4v2h12.17l-5.58 5.59L12 20l8-8z"></path></svg>Students</div></a><a href="/edu/residency-fellowships/" class="navigation-header-links__header-link" aria-label="Navigate to Residents & Fellows page"><div class="navigation-header-links__link-hover"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-header-links__link-icon"><path fill="none" d="M0 0h24v24H0z"></path><path d="m12 4-1.41 1.41L16.17 11H4v2h12.17l-5.58 5.59L12 20l8-8z"></path></svg>Residents & Fellows</div></a><a href="https://yalemedicine.org" class="navigation-header-links__header-link" aria-label="Navigate to Patients page"><div class="navigation-header-links__link-hover"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-header-links__link-icon"><path fill="none" d="M0 0h24v24H0z"></path><path d="m12 4-1.41 1.41L16.17 11H4v2h12.17l-5.58 5.59L12 20l8-8z"></path></svg>Patients</div></a><a href="/research/" class="navigation-header-links__header-link" aria-label="Navigate to Researchers page"><div class="navigation-header-links__link-hover"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-header-links__link-icon"><path fill="none" d="M0 0h24v24H0z"></path><path d="m12 4-1.41 1.41L16.17 11H4v2h12.17l-5.58 5.59L12 20l8-8z"></path></svg>Researchers</div></a><a href="/alumni/" class="navigation-header-links__header-link" aria-label="Navigate to Alumni page"><div class="navigation-header-links__link-hover"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-header-links__link-icon"><path fill="none" d="M0 0h24v24H0z"></path><path d="m12 4-1.41 1.41L16.17 11H4v2h12.17l-5.58 5.59L12 20l8-8z"></path></svg>Alumni</div></a></div></nav><div></div></div></div><div class="base-header__navigation"><div class="base-header__navigation-content--desktop"><div class="base-header__navigation-left-content"><div class="department-header__navigation-content"><nav class="department-header__breadcrumbs" aria-label="Navigation breadcrumbs"><ul class="department-header__breadcrumb-list"><li><a href="/" class="department-header__breadcrumb-link">Yale School of Medicine</a><span class="department-header__slash-delimiter">/ </span></li></ul></nav><div class="department-header__department-link-container"><a href="/center-clinical-investigation" class="department-header__department-link">Yale Center for Clinical Investigation</a><div class="base-header__navigation-menu-button"><div class="navigation-menu-button__container"><button class="navigation-menu-button navigation-menu-button--open" type="button" aria-label="Menu"><div class="navigation-menu-button__hamburger"><span class="navigation-menu-button__hamburger-line"></span><span class="navigation-menu-button__hamburger-line"></span><span class="navigation-menu-button__hamburger-line"></span></div><div class="navigation-menu-button__text">MENU</div></button></div></div></div></div></div><div class="base-header__navigation-right-content"><div class="base-header__navigation-search-button"></div></div></div><div class="base-header__navigation-content--mobile"><div class="base-header__navigation-left-content"><button type="button" class="base-header__navigation-dropdown-button" aria-label="Go to the main page"><svg xmlns="http://www.w3.org/2000/svg" aria-label="Yale School of Medicine" viewBox="0 0 384.2 29.1" focusable="false" class="site-wordmark__icon site-wordmark__icon--mode-ysm base-header__navigation-dropdown-logo"><desc>Yale School of Medicine</desc><path d="m22.3 6.1-6.8 11.5v7.7c.8 1.9 2.8 2.1 4.7 2.2v1.1H6.8v-1.1c1.9-.1 4.2-.4 4.8-1.6v-8l-7-11.8C3.5 4.2 2.3 3.5 0 3.4V2.3h11.6v1.1c-2.2.1-2.9.5-3.5 1l6.5 11.2 6.3-11.1c-.7-.5-1.5-1-3.7-1.1V2.3h9.9v1.1c-2.2 0-3.6.8-4.8 2.7M35.9 29c-2.2 0-3.3-1.5-3.4-2.6-1.4 1.5-3.2 2.6-5 2.6-2.2 0-4.1-1.4-4.1-3.7 0-1.2.3-2.4.9-3.3l8.2-3v-3.1c0-1.9-.9-3.6-2.7-3.6-1.1 0-2.2 1.4-2.3 3.5l-3.7.6V16c1.2-3.7 5.3-5.2 7.3-5.2 3.8 0 5.1 2 5.1 5.1l-.1 8.7c0 1.7.9 2.1 1.7 2.1.7 0 1.3-.4 2.1-1.2v1.2c-.9 1-2.5 2.3-4 2.3m-8.3-6.8c-.2.7-.3 1.2-.3 2.2 0 1.2.7 2.5 2.1 2.5 1.2 0 1.9-.4 3.1-1.3V20c-1.1.5-3.7 1.7-4.9 2.2m12.7 6.4v-1c1.9-.1 2.4-.5 2.7-1.2V5c0-1.4-.2-2-3.1-2.2v-.9L47.5 0l.2.7-1.2 1.5v24.2c.4.8 1.2 1.1 2.9 1.2v1zm19.1.4c-4.3 0-7.7-3.4-7.7-8.2 0-5.9 3.6-9.9 8.7-9.9 4.1 0 6.4 2.3 6.4 6v.7l-11.2-.1c-.1.5-.1 1.2-.1 2.1 0 4.2 2.7 7 6.2 7 2.1 0 3.2-.7 4.8-2.2l.6 1c-2.4 2.1-4.3 3.6-7.7 3.6m.4-16.9c-2.1 0-3.5 1.7-4 4.3l7.3-.1c-.1-2.2-1.4-4.2-3.3-4.2M83.4 29.1c-2.1 0-3.8-.6-4.9-1l-.5-4.4h.7c.2 1.1 1 2.5 2 3.2.6.5 1.9 1.2 3 1.2 2.2 0 3.3-1.4 3.3-2.8 0-1.9-1.2-2.4-3.2-3.2-3.8-1.6-5.2-2.6-5.2-5.2 0-2.9 2.9-4.8 6.7-4.8 1.8 0 3.2.5 4.1.9v4.3h-.7c-.1-1.1-.5-2.5-1.5-3.1-.4-.2-1.4-.9-2.6-.9-2.1 0-3.2 1.3-3.2 2.6 0 1.7.9 2.4 3.5 3.4 3.5 1.4 5 2.5 5 5 0 2.9-2.9 4.8-6.5 4.8m25.1-1c-2 .6-2.6.9-5.7.9-5.3 0-9.2-3.8-9.2-8.7 0-5 4.1-8.4 9.2-8.4 2.6 0 4 .5 5.9.9v4.5h-.7c-.1-1.1-.6-2.4-1.5-3-.5-.3-1.7-1.3-3.9-1.3-3.7 0-5.8 3.1-5.8 6.7 0 4.8 2.7 8.2 7 8.2 1.4 0 2.4-.6 2.8-.9 1-.8 1.7-2 2-3.2l.8.1zm15.4.6V28c1.2 0 2.2-.4 2.5-.9V21h-8.8v6.1c.2.5 1.3.8 2.5.9v.7h-7.8V28c1.1 0 2.3-.4 2.5-.9V13.9c-.2-.5-1.3-.8-2.5-.9v-.7h7.8v.7c-1.1.1-2.3.4-2.5.9v5.7h8.8v-5.7c-.3-.5-1.3-.8-2.5-.9v-.7h7.9v.7c-1.2.1-2.2.4-2.5.9v13.2c.3.5 1.3.8 2.5.9v.7zm18.9.4c-5.2 0-8.2-3.6-8.2-8.5 0-5 4.2-8.6 9.3-8.6 5.3 0 8.2 3.6 8.2 8.4 0 5.1-4.1 8.7-9.3 8.7m-.3-16c-2.4 0-4.8 2.7-4.8 6.7 0 4.7 2.3 8.1 6.3 8.1 2.6 0 5-2.6 5-6.7 0-4.9-2.5-8.1-6.5-8.1m21.4 16c-5.2 0-8.2-3.6-8.2-8.5 0-5 4.2-8.6 9.3-8.6 5.3 0 8.2 3.6 8.2 8.4 0 5.1-4.1 8.7-9.3 8.7m-.3-16c-2.4 0-4.8 2.7-4.8 6.7 0 4.7 2.3 8.1 6.3 8.1 2.6 0 5-2.6 5-6.7 0-4.9-2.5-8.1-6.5-8.1m11.9 15.6V28c1-.1 2.6-.3 3-1.2V13.9c-.2-.5-1.3-.8-2.5-.9v-.7h8.1v.7c-1.1.1-2.5.4-2.7.9v13.5l4.7-.1c1.8 0 2.9-1.7 2.9-3.9h.7v5.3zm33 .4c-5.2 0-8.2-3.6-8.2-8.5 0-5 4.2-8.6 9.3-8.6 5.3 0 8.2 3.6 8.2 8.4.1 5.1-4.1 8.7-9.3 8.7m-.3-16c-2.4 0-4.8 2.7-4.8 6.7 0 4.7 2.3 8.1 6.3 8.1 2.6 0 5-2.6 5-6.7 0-4.9-2.5-8.1-6.5-8.1m24.4 3.4c-.1-2.3-1-2.9-3-2.9H226V20l3.5-.1c1.7-.1 2.4-.1 2.7-2h.7v5.5h-.7c-.2-2.1-.9-2.1-2.6-2.1h-3.5v5.5c.3.8 1.8 1.2 3 1.3v.7h-8.6V28c1.1-.1 2.4-.3 2.7-1.1V14c-.2-.6-1.4-.9-2.6-.9v-.7h10.7c.6 0 1.1 0 1.5-.2h.6v4.3zm26.2 12.2V28c1.2-.1 2.5-.4 2.7-.9l-.5-9.5v-2.7l-.8 2.1-5.2 11.7h-1l-4.5-12.3-.7-2-.1 1.8-.7 10.6c.2.5 1.4 1 2.6 1.1v.7h-6.7V28c1.2-.1 2.3-.6 2.6-1.1l.7-9.2c.1-.9.2-2.8.2-2.9V14c-.3-.4-1.1-.8-2.3-.9v-.7h5.8l.8 2.5 3.7 10.2 4.2-9.9 1.1-2.7h5.2v.5c-1.2.1-2.1.4-2.3.8v.6c0 .3.1 2.3.2 3.1l.5 9.5c.3.5 1.4.8 2.5.9v.7h-8zm16.5 0-5.8.1v-.7c1.2-.1 2.9-.4 3.3-1.2v-13c-.2-.5-1.3-.8-2.5-.9v-.7H281c.7 0 1.2-.1 1.5-.2h.6v4.3h-.7c-.1-2.3-1-2.9-3-2.9h-3.7v6.1h3.5c1.8 0 2.5 0 2.7-1.9h.6V23h-.7c-.2-2.1-.8-2.1-2.7-2.1h-3.5v5.6c.1.3.2.7.7.9l4.1-.1c1.7 0 2.9-.8 2.9-3h.6v4.3h-8.6zm20.8 0h-8.6V28c1.1 0 2.4-.4 2.6-.9V13.9c-.2-.5-1.5-.8-2.7-.9v-.7c3-.1 5.9-.3 8.2-.3 5.9 0 9.4 3 9.4 8s-3.9 8.8-8.9 8.7M294.5 13H293v13.9c.3.4 1.7.8 2.7.8 4.1 0 6.1-2.8 6.1-6.8 0-5.3-2.8-7.9-7.3-7.9m13.1 15.7V28c1.2-.1 2.4-.4 2.6-.9V13.9c-.2-.5-1.4-.8-2.6-.9v-.7h8.2v.7c-1.2.1-2.4.4-2.6.9V27c.2.5 1.4.8 2.6.9v.7h-8.2zm25.6-.6c-2 .6-2.6.9-5.7.9-5.3 0-9.2-3.8-9.2-8.7 0-5 4.1-8.4 9.2-8.4 2.6 0 4 .5 5.9.9v4.5h-.7c-.1-1.1-.6-2.4-1.5-3-.5-.3-1.7-1.3-3.9-1.3-3.7 0-5.8 3.1-5.8 6.7 0 4.8 2.7 8.2 7 8.2 1.4 0 2.4-.6 2.8-.9 1-.8 1.7-2 2-3.2l.8.1zm3.8.6V28c1.2-.1 2.4-.4 2.6-.9V13.9c-.2-.5-1.4-.8-2.6-.9v-.7h8.2v.7c-1.2.1-2.4.4-2.6.9V27c.2.5 1.4.8 2.6.9v.7H337zm27.8-14.5V24c0 1.4.1 3.7.2 4.9h-1.6l-10-12.3-1.1-1.7.1 1.5v5.9c0 1.4.1 3.4.2 4.5.2.5 1.7 1 2.9 1.1v.7h-7.1V28c1.2-.1 2.3-.6 2.5-1.1v-9.2c0-1.3 0-2.6-.1-3.5-.3-.5-1.3-1-2.5-1.1v-.7h5.2l1.5 1.9 8.4 10.3v-5.9c0-1.4-.1-3.6-.1-4.4-.2-.5-1.7-1.1-2.9-1.1v-.7h7.1v.5c-1.3.1-2.4.6-2.7 1.2m10.7 14.5-5.8.1v-.7c1.2-.1 2.9-.4 3.3-1.2v-13c-.2-.5-1.3-.8-2.5-.9v-.7h10.7c.7 0 1.2-.1 1.5-.2h.6v4.3h-.7c-.1-2.3-1-2.9-3-2.9h-3.7v6.1h3.5c1.8 0 2.5 0 2.7-1.9h.6V23h-.7c-.2-2.1-.8-2.1-2.7-2.1h-3.5v5.6c.1.3.2.7.7.9l4.1-.1c1.7 0 2.9-.8 2.9-3h.6v4.3h-8.6z"></path></svg><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="base-header__navigation-dropdown-icon"><path d="M23.25 7.311 12.53 18.03a.75.75 0 0 1-1.06 0L.75 7.311" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round;stroke-width:1.5px;fill-rule:evenodd"></path></svg></button><div></div></div><div class="base-header__navigation-right-content"><div class="base-header__navigation-menu-button"><div class="navigation-menu-button__container"><button class="navigation-menu-button navigation-menu-button--open" type="button" aria-label="Menu"><div class="navigation-menu-button__hamburger"><span class="navigation-menu-button__hamburger-line"></span><span class="navigation-menu-button__hamburger-line"></span><span class="navigation-menu-button__hamburger-line"></span></div><div class="navigation-menu-button__text">MENU</div></button></div></div></div></div></div><div class="base-header__navigation-panel"><div class="navigation-panel__wrapper navigation-panel__wrapper--hidden"><nav class="navigation-panel__top-container" aria-label="Navigation Panel"><div class="navigation-panel__header-container"><a href="/center-clinical-investigation" class="navigation-panel__header-text">Yale Center for Clinical Investigation</a></div></nav><div class="navigation-panel__grid-container"><div class="navigation-panel__grid-column"><ul><li class="navigation-panel__grid-column-list-item"><div class="navigation-panel__grid-item"><div class="navigation-panel-sub-panel" aria-level="0"><div id="sub-panel__heading-0" aria-controls="sub-panel__body-0" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item navigation-panel-item--height"><a href="/center-clinical-investigation/about" class="navigation-panel-item__option-text navigation-panel-item__option-text--parent" aria-label="Navigate to About YCCI page"><span class="navigation-panel-item__option-text-link navigation-panel-item__option-text-link--parent">About YCCI</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open About YCCI menu item."><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-0" class="navigation-panel-sub-panel__body"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/about/mission" class="navigation-panel-item__option-text" aria-label="Navigate to Mission page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Mission</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="1"><div id="sub-panel__heading-0-1" aria-controls="sub-panel__body-0-1" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/about/tradition-of-discovery" class="navigation-panel-item__option-text" aria-label="Navigate to A Tradition of Discovery page" tabindex="-1"><span class="navigation-panel-item__option-text-link">A Tradition of Discovery</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open A Tradition of Discovery menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-0-1" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/about/tradition-of-discovery/history-of-firsts" class="navigation-panel-item__option-text" aria-label="Navigate to A History of Firsts page" tabindex="-1"><span class="navigation-panel-item__option-text-link">A History of Firsts</span></a></div></li></ul></div></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="1"><div id="sub-panel__heading-0-2" aria-controls="sub-panel__body-0-2" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/about/collaboration" class="navigation-panel-item__option-text" aria-label="Navigate to Collaborations page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Collaborations</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open Collaborations menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-0-2" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/about/collaboration/community-practices" class="navigation-panel-item__option-text" aria-label="Navigate to Collaborations with Community Practices page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Collaborations with Community Practices</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/about/collaboration/fda" class="navigation-panel-item__option-text" aria-label="Navigate to Collaborations with the FDA page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Collaborations with the FDA</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/about/collaboration/other-institutions" class="navigation-panel-item__option-text" aria-label="Navigate to Collaborations with Other Institutions page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Collaborations with Other Institutions</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/about/collaboration/equitable-breakthroughs" class="navigation-panel-item__option-text" aria-label="Navigate to Equitable Breakthroughs in Medicine Development (EQBMED) page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Equitable Breakthroughs in Medicine Development (EQBMED)</span></a></div></li></ul></div></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/about/leadership" class="navigation-panel-item__option-text" aria-label="Navigate to Leadership & Faculty page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Leadership & Faculty</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/about/job-opportunities" class="navigation-panel-item__option-text" aria-label="Navigate to Job Opportunities page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Job Opportunities</span></a></div></li></ul></div></div></div></li><li class="navigation-panel__grid-column-list-item"><div class="navigation-panel__grid-item"><div class="navigation-panel-item navigation-panel-item--height"><a href="https://medicine.yale.edu/ycci/clinicaltrials/" class="navigation-panel-item__option-text navigation-panel-item__option-text--parent" aria-label="Navigate to Find a Study page"><span class="navigation-panel-item__option-text-link navigation-panel-item__option-text-link--parent">Find a Study</span></a></div></div></li></ul></div><div class="navigation-panel__grid-column"><ul><li class="navigation-panel__grid-column-list-item"><div class="navigation-panel__grid-item"><div class="navigation-panel-sub-panel" aria-level="0"><div id="sub-panel__heading-1" aria-controls="sub-panel__body-1" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item navigation-panel-item--height"><a href="/center-clinical-investigation/research-services" class="navigation-panel-item__option-text navigation-panel-item__option-text--parent" aria-label="Navigate to Research Services page"><span class="navigation-panel-item__option-text-link navigation-panel-item__option-text-link--parent">Research Services</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open Research Services menu item."><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-1" class="navigation-panel-sub-panel__body"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="1"><div id="sub-panel__heading-1-0" aria-controls="sub-panel__body-1-0" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team" class="navigation-panel-item__option-text" aria-label="Navigate to Services by Team page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Services by Team</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open Services by Team menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-1-0" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="2"><div id="sub-panel__heading-1-0-0" aria-controls="sub-panel__body-1-0-0" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/protocol-design" class="navigation-panel-item__option-text" aria-label="Navigate to Protocol Design, Development & Feasibility page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Protocol Design, Development & Feasibility</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open Protocol Design, Development & Feasibility menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-1-0-0" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/protocol-design/study-design-biostatistics" class="navigation-panel-item__option-text" aria-label="Navigate to Study Design, & Biostatistics page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Study Design, & Biostatistics</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/protocol-design/clinical-trials-project-management" class="navigation-panel-item__option-text" aria-label="Navigate to Clinical Trials Project Management page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Clinical Trials Project Management</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/protocol-design/clinical-data-management" class="navigation-panel-item__option-text" aria-label="Navigate to Clinical Data Management page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Clinical Data Management</span></a></div></li></ul></div></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="2"><div id="sub-panel__heading-1-0-1" aria-controls="sub-panel__body-1-0-1" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/protocol-activation" class="navigation-panel-item__option-text" aria-label="Navigate to Protocol Activation & Lifecycle Management page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Protocol Activation & Lifecycle Management</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open Protocol Activation & Lifecycle Management menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-1-0-1" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/protocol-activation/coverage-analysis" class="navigation-panel-item__option-text" aria-label="Navigate to Coverage Analysis page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Coverage Analysis</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/protocol-activation/budget-financial-management" class="navigation-panel-item__option-text" aria-label="Navigate to Budget & Financial Management page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Budget & Financial Management</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/protocol-activation/regulatory-process-support" class="navigation-panel-item__option-text" aria-label="Navigate to Regulatory Process Support page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Regulatory Process Support</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/protocol-activation/oncore-protocol-subject-management" class="navigation-panel-item__option-text" aria-label="Navigate to OnCore Protocol & Subject Management page" tabindex="-1"><span class="navigation-panel-item__option-text-link">OnCore Protocol & Subject Management</span></a></div></li></ul></div></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="2"><div id="sub-panel__heading-1-0-2" aria-controls="sub-panel__body-1-0-2" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/operations" class="navigation-panel-item__option-text" aria-label="Navigate to Clinical Research Operations page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Clinical Research Operations</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open Clinical Research Operations menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-1-0-2" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/operations/bionutrition-unit" class="navigation-panel-item__option-text" aria-label="Navigate to YNHH Bionutrition Unit page" tabindex="-1"><span class="navigation-panel-item__option-text-link">YNHH Bionutrition Unit</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/operations/clinical-services" class="navigation-panel-item__option-text" aria-label="Navigate to Clinical Services page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Clinical Services</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/operations/clinical-research-support-lab-services" class="navigation-panel-item__option-text" aria-label="Navigate to Clinical Research Support Lab Services page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Clinical Research Support Lab Services</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/operations/investigational-drug-service" class="navigation-panel-item__option-text" aria-label="Navigate to YNHH Investigational Drug Service page" tabindex="-1"><span class="navigation-panel-item__option-text-link">YNHH Investigational Drug Service</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="3"><div id="sub-panel__heading-1-0-2-4" aria-controls="sub-panel__body-1-0-2-4" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/operations/outpatient-inpatient-facilities" class="navigation-panel-item__option-text" aria-label="Navigate to Outpatient & Inpatient Facilities page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Outpatient & Inpatient Facilities</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open Outpatient & Inpatient Facilities menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-1-0-2-4" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/operations/outpatient-inpatient-facilities/csru" class="navigation-panel-item__option-text" aria-label="Navigate to Church Street Research Unit (CSRU) page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Church Street Research Unit (CSRU)</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/operations/outpatient-inpatient-facilities/wcru" class="navigation-panel-item__option-text" aria-label="Navigate to West Campus Research Unit (WCRU) page" tabindex="-1"><span class="navigation-panel-item__option-text-link">West Campus Research Unit (WCRU)</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/operations/outpatient-inpatient-facilities/mrrc" class="navigation-panel-item__option-text" aria-label="Navigate to Magnetic Resonance Research Center (MRRC) page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Magnetic Resonance Research Center (MRRC)</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/operations/outpatient-inpatient-facilities/hru" class="navigation-panel-item__option-text" aria-label="Navigate to Hospital Research Unit (HRU) page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Hospital Research Unit (HRU)</span></a></div></li></ul></div></div></li></ul></div></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="2"><div id="sub-panel__heading-1-0-3" aria-controls="sub-panel__body-1-0-3" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory" class="navigation-panel-item__option-text" aria-label="Navigate to QA, Compliance & Regulatory Affairs page" tabindex="-1"><span class="navigation-panel-item__option-text-link">QA, Compliance & Regulatory Affairs</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open QA, Compliance & Regulatory Affairs menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-1-0-3" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/clinicaltrials.gov-support-services" class="navigation-panel-item__option-text" aria-label="Navigate to Clinicaltrials.gov Support Services page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Clinicaltrials.gov Support Services</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/clinical-research-billing-compliance" class="navigation-panel-item__option-text" aria-label="Navigate to Clinical Research Billing Compliance page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Clinical Research Billing Compliance</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="3"><div id="sub-panel__heading-1-0-3-2" aria-controls="sub-panel__body-1-0-3-2" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/ind-ide-support" class="navigation-panel-item__option-text" aria-label="Navigate to IND/IDE Support page" tabindex="-1"><span class="navigation-panel-item__option-text-link">IND/IDE Support</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open IND/IDE Support menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-1-0-3-2" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/ind-ide-support/ind-training" class="navigation-panel-item__option-text" aria-label="Navigate to IND Training page" tabindex="-1"><span class="navigation-panel-item__option-text-link">IND Training</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/ind-ide-support/ide-training" class="navigation-panel-item__option-text" aria-label="Navigate to IDE Training page" tabindex="-1"><span class="navigation-panel-item__option-text-link">IDE Training</span></a></div></li></ul></div></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="3"><div id="sub-panel__heading-1-0-3-3" aria-controls="sub-panel__body-1-0-3-3" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/quality-assurance-monitoring" class="navigation-panel-item__option-text" aria-label="Navigate to Quality Assurance & Monitoring page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Quality Assurance & Monitoring</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open Quality Assurance & Monitoring menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-1-0-3-3" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/quality-assurance-monitoring/audit-preparedness" class="navigation-panel-item__option-text" aria-label="Navigate to Audit Preparedness page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Audit Preparedness</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/quality-assurance-monitoring/monitoring" class="navigation-panel-item__option-text" aria-label="Navigate to Monitoring page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Monitoring</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/quality-assurance-monitoring/committees" class="navigation-panel-item__option-text" aria-label="Navigate to Committees page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Committees</span></a></div></li></ul></div></div></li></ul></div></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/financial-services" class="navigation-panel-item__option-text" aria-label="Navigate to Clinical Research Finance page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Clinical Research Finance</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="2"><div id="sub-panel__heading-1-0-5" aria-controls="sub-panel__body-1-0-5" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/community-engagement-and-recruitment" class="navigation-panel-item__option-text" aria-label="Navigate to Community Engagement & Participant Recruitment page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Community Engagement & Participant Recruitment</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open Community Engagement & Participant Recruitment menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-1-0-5" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="3"><div id="sub-panel__heading-1-0-5-0" aria-controls="sub-panel__body-1-0-5-0" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/community-engagement-and-recruitment/engagement" class="navigation-panel-item__option-text" aria-label="Navigate to Community Engagement page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Community Engagement</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open Community Engagement menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-1-0-5-0" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/community-engagement-and-recruitment/engagement/research" class="navigation-panel-item__option-text" aria-label="Navigate to Research in the Community page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Research in the Community</span></a></div></li></ul></div></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/services-by-team/community-engagement-and-recruitment/participant-recruitment" class="navigation-panel-item__option-text" aria-label="Navigate to Participant Recruitment page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Participant Recruitment</span></a></div></li></ul></div></div></li></ul></div></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="1"><div id="sub-panel__heading-1-1" aria-controls="sub-panel__body-1-1" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/resources-documents" class="navigation-panel-item__option-text" aria-label="Navigate to Resources & Documents page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Resources & Documents</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open Resources & Documents menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-1-1" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/resources-documents/training-documents" class="navigation-panel-item__option-text" aria-label="Navigate to Training Documents page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Training Documents</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/resources-documents/training-videos" class="navigation-panel-item__option-text" aria-label="Navigate to Training Videos page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Training Videos</span></a></div></li></ul></div></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="1"><div id="sub-panel__heading-1-2" aria-controls="sub-panel__body-1-2" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/systems" class="navigation-panel-item__option-text" aria-label="Navigate to Systems & Infrastructure page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Systems & Infrastructure</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open Systems & Infrastructure menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-1-2" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="2"><div id="sub-panel__heading-1-2-0" aria-controls="sub-panel__body-1-2-0" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/systems/epic" class="navigation-panel-item__option-text" aria-label="Navigate to Epic (EHR) page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Epic (EHR)</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open Epic (EHR) menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-1-2-0" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/systems/epic/epic-data-requests" class="navigation-panel-item__option-text" aria-label="Navigate to Epic Data Requests page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Epic Data Requests</span></a></div></li></ul></div></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/systems/redcap" class="navigation-panel-item__option-text" aria-label="Navigate to REDCap page" tabindex="-1"><span class="navigation-panel-item__option-text-link">REDCap</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/systems/ereg" class="navigation-panel-item__option-text" aria-label="Navigate to Advarra eREg page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Advarra eREg</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/systems/hugo" class="navigation-panel-item__option-text" aria-label="Navigate to Hugo page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Hugo</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/systems/epic-care" class="navigation-panel-item__option-text" aria-label="Navigate to EpicCare (login) page" tabindex="-1"><span class="navigation-panel-item__option-text-link">EpicCare (login)</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/systems/edc" class="navigation-panel-item__option-text" aria-label="Navigate to Advarra eSource + EDC page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Advarra eSource + EDC</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/systems/evaluation" class="navigation-panel-item__option-text" aria-label="Navigate to Evaluation page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Evaluation</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/research-services/systems/acrobat-sign" class="navigation-panel-item__option-text" aria-label="Navigate to Acrobat Sign page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Acrobat Sign</span></a></div></li></ul></div></div></li></ul></div></div></div></li><li class="navigation-panel__grid-column-list-item"><div class="navigation-panel__grid-item"><div class="navigation-panel-item navigation-panel-item--height"><a href="/center-clinical-investigation/news-events" class="navigation-panel-item__option-text navigation-panel-item__option-text--parent" aria-label="Navigate to News & Events page"><span class="navigation-panel-item__option-text-link navigation-panel-item__option-text-link--parent">News & Events</span></a></div></div></li></ul></div><div class="navigation-panel__grid-column"><ul><li class="navigation-panel__grid-column-list-item"><div class="navigation-panel__grid-item"><div class="navigation-panel-sub-panel" aria-level="0"><div id="sub-panel__heading-2" aria-controls="sub-panel__body-2" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item navigation-panel-item--height"><a href="/center-clinical-investigation/ctsa-funding" class="navigation-panel-item__option-text navigation-panel-item__option-text--parent" aria-label="Navigate to CTSA & Funding page"><span class="navigation-panel-item__option-text-link navigation-panel-item__option-text-link--parent">CTSA & Funding</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open CTSA & Funding menu item."><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-2" class="navigation-panel-sub-panel__body"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/ctsa-funding/initiatives" class="navigation-panel-item__option-text" aria-label="Navigate to CTSA Initiatives page" tabindex="-1"><span class="navigation-panel-item__option-text-link">CTSA Initiatives</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/ctsa-funding/faculty-awards" class="navigation-panel-item__option-text" aria-label="Navigate to Scholar Awards for Junior Faculty page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Scholar Awards for Junior Faculty</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/ctsa-funding/multidisciplinary-pre-doctoral-training-program" class="navigation-panel-item__option-text" aria-label="Navigate to Multidisciplinary Pre-Doctoral Training Program page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Multidisciplinary Pre-Doctoral Training Program</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/ctsa-funding/multidisciplinary-post-doctoral-training-program" class="navigation-panel-item__option-text" aria-label="Navigate to Multidisciplinary Post-Doctoral Training Program page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Multidisciplinary Post-Doctoral Training Program</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/ctsa-funding/pilot-programs-awards" class="navigation-panel-item__option-text" aria-label="Navigate to Pilot Programs & Awards page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Pilot Programs & Awards</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/ctsa-funding/milestones" class="navigation-panel-item__option-text" aria-label="Navigate to Milestones page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Milestones</span></a></div></li></ul></div></div></div></li></ul></div><div class="navigation-panel__grid-column"><ul><li class="navigation-panel__grid-column-list-item"><div class="navigation-panel__grid-item"><div class="navigation-panel-sub-panel" aria-level="0"><div id="sub-panel__heading-3" aria-controls="sub-panel__body-3" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item navigation-panel-item--height"><a href="/center-clinical-investigation/workforce-development-education" class="navigation-panel-item__option-text navigation-panel-item__option-text--parent" aria-label="Navigate to Workforce Development & Education page"><span class="navigation-panel-item__option-text-link navigation-panel-item__option-text-link--parent">Workforce Development & Education</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open Workforce Development & Education menu item."><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-3" class="navigation-panel-sub-panel__body"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="1"><div id="sub-panel__heading-3-0" aria-controls="sub-panel__body-3-0" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/trainees" class="navigation-panel-item__option-text" aria-label="Navigate to Trainees page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Trainees</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open Trainees menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-3-0" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="2"><div id="sub-panel__heading-3-0-0" aria-controls="sub-panel__body-3-0-0" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/trainees/pre-doctoral" class="navigation-panel-item__option-text" aria-label="Navigate to Pre-Doctoral page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Pre-Doctoral</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open Pre-Doctoral menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-3-0-0" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/trainees/pre-doctoral/awardees" class="navigation-panel-item__option-text" aria-label="Navigate to Awardees page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Awardees</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/trainees/pre-doctoral/faqs" class="navigation-panel-item__option-text" aria-label="Navigate to FAQ's page" tabindex="-1"><span class="navigation-panel-item__option-text-link">FAQ's</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/trainees/pre-doctoral/representative-publications" class="navigation-panel-item__option-text" aria-label="Navigate to Representative Publications page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Representative Publications</span></a></div></li></ul></div></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="2"><div id="sub-panel__heading-3-0-1" aria-controls="sub-panel__body-3-0-1" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/trainees/post-doctoral" class="navigation-panel-item__option-text" aria-label="Navigate to Post Doctoral page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Post Doctoral</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open Post Doctoral menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-3-0-1" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/trainees/post-doctoral/faqs" class="navigation-panel-item__option-text" aria-label="Navigate to FAQ's page" tabindex="-1"><span class="navigation-panel-item__option-text-link">FAQ's</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/trainees/post-doctoral/awardees" class="navigation-panel-item__option-text" aria-label="Navigate to Awardees page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Awardees</span></a></div></li></ul></div></div></li></ul></div></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/clinical-research-staff-training" class="navigation-panel-item__option-text" aria-label="Navigate to Clinical Research Staff Training page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Clinical Research Staff Training</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="1"><div id="sub-panel__heading-3-2" aria-controls="sub-panel__body-3-2" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/internship-opportunities" class="navigation-panel-item__option-text" aria-label="Navigate to Internship Opportunities page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Internship Opportunities</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open Internship Opportunities menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-3-2" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/internship-opportunities/exposures-program" class="navigation-panel-item__option-text" aria-label="Navigate to Exposures Program page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Exposures Program</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/internship-opportunities/post-baccalaureate-internship" class="navigation-panel-item__option-text" aria-label="Navigate to Post Baccalaureate Internship page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Post Baccalaureate Internship</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/internship-opportunities/summer-enrichment-research-experience" class="navigation-panel-item__option-text" aria-label="Navigate to Yale Summer Enrichment Research Experience page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Yale Summer Enrichment Research Experience</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/internship-opportunities/interns" class="navigation-panel-item__option-text" aria-label="Navigate to Past and Current YCCI Interns page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Past and Current YCCI Interns</span></a></div></li></ul></div></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="1"><div id="sub-panel__heading-3-3" aria-controls="sub-panel__body-3-3" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/faculty" class="navigation-panel-item__option-text" aria-label="Navigate to Faculty page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Faculty</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open Faculty menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-3-3" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-sub-panel navigation-panel-sub-panel--nested" aria-level="2"><div id="sub-panel__heading-3-3-0" aria-controls="sub-panel__body-3-3-0" class="navigation-panel-sub-panel__header" aria-expanded="false"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/faculty/junior-faculty-scholars" class="navigation-panel-item__option-text" aria-label="Navigate to Jr Faculty Scholars page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Jr Faculty Scholars</span></a><button class="navigation-panel-item__button" type="button" aria-label="Open Jr Faculty Scholars menu item." tabindex="-1"><div class="navigation-panel-item__icon navigation-panel-item__button-icon"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="navigation-panel-item__icon"><path d="M12 1v22M23 12H1" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></div></button></div></div><div id="sub-panel__body-3-3-0" class="navigation-panel-sub-panel__body navigation-panel-sub-panel__body--nested"><ul><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/faculty/junior-faculty-scholars/scholars" class="navigation-panel-item__option-text" aria-label="Navigate to Current and Past Scholars page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Current and Past Scholars</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/faculty/junior-faculty-scholars/representative-publications" class="navigation-panel-item__option-text" aria-label="Navigate to Representative Publications page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Representative Publications</span></a></div></li></ul></div></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/faculty/phd-training" class="navigation-panel-item__option-text" aria-label="Navigate to PhD Training page" tabindex="-1"><span class="navigation-panel-item__option-text-link">PhD Training</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/faculty/mentoring" class="navigation-panel-item__option-text" aria-label="Navigate to Mentoring page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Mentoring</span></a></div></li><li class="navigation-panel-sub-panel__body-list-item"><div class="navigation-panel-item"><a href="/center-clinical-investigation/workforce-development-education/faculty/team-science" class="navigation-panel-item__option-text" aria-label="Navigate to Team Science page" tabindex="-1"><span class="navigation-panel-item__option-text-link">Team Science</span></a></div></li></ul></div></div></li></ul></div></div></div></li></ul></div></div></div></div></div><div class="base-header__mobile-navigation-dropdown"><div class="mobile-navigation-dropdown"><div class="mobile-navigation-dropdown__home-link"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="mobile-navigation-dropdown__home-icon"><path d="M3.753 13.944v8.25h6v-6a1.5 1.5 0 0 1 1.5-1.5h1.5a1.5 1.5 0 0 1 1.5 1.5v6h6v-8.25M.753 12.444 10.942 2.255a1.5 1.5 0 0 1 2.122 0l10.189 10.189" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round;stroke-width:1.5px"></path></svg><a href="/" class="mobile-navigation-dropdown__link">YSM Home</a></div><p class="mobile-navigation-dropdown__title">INFORMATION FOR</p><ul><li><a href="/about/" class="mobile-navigation-dropdown__link">About YSM</a></li><li><a href="/faculty/" class="mobile-navigation-dropdown__link">Faculty</a></li><li><a href="/myysm/" class="mobile-navigation-dropdown__link">Staff</a></li><li><a href="/edu/" class="mobile-navigation-dropdown__link">Students</a></li><li><a href="/edu/residency-fellowships/" class="mobile-navigation-dropdown__link">Residents & Fellows</a></li><li><a href="https://yalemedicine.org" class="mobile-navigation-dropdown__link">Patients</a></li><li><a href="/research/" class="mobile-navigation-dropdown__link">Researchers</a></li><li><a href="/alumni/" class="mobile-navigation-dropdown__link">Alumni</a></li></ul></div></div></div></div><div style="margin-top:0px" class="base-page"><main class="page-container" tabindex="-1" id="page-container"><div class="content content--with-sidebar page__content-container"><div class="component-wrapper component-wrapper--all"><section class="article-details" aria-label="Article Details"><article><div class="article-header article-header--with-sidebar"><div class="article-header__row"><h1 class="article-header__title">Parkinson’s Disease Associated With Neuroinflammation in the Brain, New Analyses Reveal </h1></div><div class="article-header__publication-info"><div class="news-details__date">November 07, 2024</div><div class="news-details__submitter">by <a href="/center-clinical-investigation/profile/isabella-backman/#links-details-section" tabindex="0" class="link link--size--small link--width--inline link--align--right link--color--black link--font--normal link--decorate-color--light-blue"><span class="link__label">Isabella Backman</span></a></div><div class="news-details__contact"></div></div><div class="article-header__share-panel"><ul class="share-panel share-panel--horizontal"><li class="share-panel__item"><button class="share-panel__link" aria-label="Share via X" type="button"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="share-panel__icon"><path d="M17.294 22.475 1.454 1.453h5.252l15.84 21.022zm4.508-21.022-8.35 8.954M2.198 22.475l8.344-8.948" style="fill:none;stroke:currentColor;stroke-width:1.5;stroke-linecap:round;stroke-linejoin:round"></path></svg></button></li><li class="share-panel__item"><button class="share-panel__link" aria-label="Share via Facebook" type="button"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="share-panel__icon"><path d="M12.5 23.5h-11a1 1 0 0 1-1-1v-21a1 1 0 0 1 1-1h21a1 1 0 0 1 1 1v21a1 1 0 0 1-1 1h-6v-9h2.559a.5.5 0 0 0 .5-.438l.375-3a.5.5 0 0 0-.5-.562H16.5V9.185A1.687 1.687 0 0 1 18.186 7.5H20a.5.5 0 0 0 .5-.5V4a.5.5 0 0 0-.5-.5h-1.814A5.69 5.69 0 0 0 12.5 9.185V10.5H10a.5.5 0 0 0-.5.5v3a.5.5 0 0 0 .5.5h2.5z" style="fill:currentColor;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></button></li><li class="share-panel__item"><button class="share-panel__link" aria-label="Share via LinkedIn" type="button"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="share-panel__icon"><path d="M6.5 22.5h-5v-13h5Zm9-9a2 2 0 0 0-2 2v7h-5v-13h5v1.485a6.3 6.3 0 0 1 3.99-1.495c2.962 0 5.01 2.2 5.01 6.355V22.5h-5v-7a2 2 0 0 0-2-2M6.5 5A2.5 2.5 0 1 1 4 2.5 2.5 2.5 0 0 1 6.5 5" style="fill:currentColor;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></button></li><li class="share-panel__item"><button type="button" aria-label="Share page via email" class="share-panel__button"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="share-panel__icon"><path d="M23.888 5.832a.18.18 0 0 0-.2.039l-9.747 9.745a2.75 2.75 0 0 1-3.888 0L.31 5.871a.18.18 0 0 0-.2-.039A.18.18 0 0 0 0 6v12a2 2 0 0 0 2 2h20a2 2 0 0 0 2-2V6a.18.18 0 0 0-.112-.168" style="fill:currentColor"></path><path d="M11.115 14.556a1.25 1.25 0 0 0 1.768 0l9.686-9.686a.5.5 0 0 0 .121-.511C22.58 4.03 22.274 4 22 4H2c-.275 0-.583.03-.691.359a.5.5 0 0 0 .121.511Z" style="fill:currentColor"></path></svg></button></li><li class="share-panel__item"><button type="button" aria-label="Print page" class="share-panel__button"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="share-panel__icon share-panel__print-icon"><path d="M5.25 17.249h-3a1.5 1.5 0 0 1-1.5-1.5v-7.5a1.5 1.5 0 0 1 1.5-1.5h19.5a1.5 1.5 0 0 1 1.5 1.5v7.5a1.5 1.5 0 0 1-1.5 1.5h-3" style="stroke-linecap:round;stroke-linejoin:round;fill:currentColor;stroke-width:.5px"></path><path d="M3.75 9.749h1.5" style="stroke-linecap:round;stroke-linejoin:round;stroke-width:1.5px;stroke-opacity:1"></path><path d="M5.25 12.749h13.5v10H5.25z" class="paper" style="stroke-linecap:round;stroke-linejoin:round;fill:currentColor;stroke-width:2"></path><path d="M18.75 6.749H5.25v-4.5a1.5 1.5 0 0 1 1.5-1.5h10.5a1.5 1.5 0 0 1 1.5 1.5Z" style="stroke-linecap:round;stroke-linejoin:round;fill:currentColor;stroke-width:.25px;stroke-opacity:1"></path></svg></button></li></ul></div></div><div class="article-content__container"><div class="article-content__item"><div class="article-content__text article-content__text--media-hidden"><p>Using groundbreaking emerging sequencing technologies, Yale School of Medicine scientists are studying human brains impacted by Parkinson’s disease in unprecedented detail. This research is bringing them closer to understanding how the life-altering condition arises.</p> <p>In a recent study, the researchers generated a cell atlas—a comprehensive reference that maps out all cell types within an organ—based on postmortem human brains from individuals with late-stage disease. Using single cell transcriptomics and proteomics, which enabled them to measure gene and protein expression, they compared how their findings differed from that found in healthy controls. Their findings revealed key differences, including that brains affected by Parkinson’s disease have greater levels of neuroinflammation. </p> <p>The researchers also compared their Parkinson’s cell atlas to a previously published one that mapped cell types found in human brains affected by Alzheimer’s disease. They found that each disease has a distinct pathology that impacts the neurons differently but common signatures in glial cells and neuroinflammation. The researchers published their findings in <a href="https://www.science.org/doi/10.1126/scitranslmed.abo1997"><em class="arx-italic-text">Science Translational Medicine</em></a> on October 30.</p> <p>The research was led by <a href="https://medicine.yale.edu/profile/le-zhang/">Le Zhang, PhD</a>, assistant professor of neurology and of neuroscience, <a href="https://medicine.yale.edu/profile/sreeganga-chandra/">Sreeganga Chandra, PhD</a>, associate professor of neurology and neuroscience, and <a href="https://medicine.yale.edu/profile/david-hafler/">David Hafler, MD</a>, the William S. and Lois Stiles Edgerly Professor of Neurology and professor of immunobiology at Yale.</p> <p>“What we really want to do is learn how to prevent Parkinson’s disease,” says Hafler, who is also chair of Yale’s Department of Neurology. “This work in the brain is one more piece of the puzzle that suggests the importance of inflammation as a cause of the disease.”</p> <p>Parkinson’s disease is a progressive neurodegenerative disorder that impacts millions of people around the world. The condition is characterized by loss of neurons in the substantia nigra, a region in the midbrain that produces dopamine. It is also associated with the formation of Lewy bodies—abnormal clumps of protein that develop inside nerve cells in the brain.</p> <p>While Parkinson’s disease is primarily known for motor symptoms that result from the degeneration of dopamine-producing neurons, it also causes prefrontal cortex dysfunction. The prefrontal cortex is the region of the brain associated with complex cognitive functions such as decision-making, attention, and working memory. This region is also significantly impacted by Alzheimer’s disease. </p> <h2>Parkinson’s disease is linked to greater levels of neuroinflammation</h2> <p>Researchers have not had much insight into the underlying pathways that contribute to the onset and progression of Parkinson’s disease. Now, in their latest study, the Yale-led team ran multiple analyses on post-mortem tissue. By focusing their investigation on the prefrontal cortex, they were able to compare their analyses to previously reported data on Alzheimer’s disease. </p> <p>The team ran two major analyses: single-cell transcriptomics and proteomics. Through single-cell transcriptomics, they isolated the nuclei of the brain cells in the prefrontal cortex and sequenced all of the RNA, known as “the transcriptome.” Then, they compared differences in gene expression found in brains with Parkinson’s disease against healthy controls. </p> <p>Using the same tissue, they also ran a proteomics analysis, in which they used an analytical technique called mass spectrometry to measure protein expression in the tissues. This enabled the researchers to understand how the expression of proteins differs in Parkinson’s disease. </p> <p>“Our study helped us understand the gene changes in Parkinson’s disease at the cell type level,” says Zhang. “By integrating this with our proteomics data, we can better understand the effects of the disease at both RNA and protein levels.”</p> <p>The researchers found that brains with Parkinson’s disease showed signs of increased neuroinflammation, including elevated levels of two kinds of immune cells known as T cells and microglia. </p> <p>Furthermore, they found that the presence of Lewy bodies was inversely correlated to the expression of a class of proteins called chaperones—these enable other proteins to fold properly and prevent them from aggregating—in excitatory neurons that regulate electrical signals in the brain. This finding could have therapeutic implications, the authors say. “If we could increase chaperone capacity in the brain, we could potentially decrease the abnormal aggregation associated with Parkinson’s,” says Chandra.</p> <p>Next, the team looked for shared features between brains with Parkinson’s disease and Alzheimer’s disease. “We wanted to compare the two most common neurodegenerative diseases,” explains Zhang. </p> <p>To their surprise, they did not find any overlap in gene expression within neurons. This suggests that the diseases likely impact neurons in distinct ways, the researchers say. “Parkinson’s and Alzheimer’s are clinically different diseases that have different mechanisms, and therefore the options to treat them will be different,” says Chandra. </p> <h2>Cell atlas will help guide future research</h2> <p>The study gave researchers important insight into how Parkinson’s disease arises. “Before the advent of these technologies, we couldn’t interrogate human tissue to get insights into disease progression,” says Chandra. “These analyses will help inform our future experiments and are a platform to raise pertinent questions that we can test.”</p> <p>The team hopes their cell atlas will help guide the studies of research teams investigating Parkinson’s disease. In their own labs, the researchers’ next steps are to apply the same methods to brains in the early stages of the condition. In addition, they are looking at the blood and spinal fluid of patients, where they have also found signs of inflammation. Based on insights from these studies, the researchers plan to conduct clinical trials aimed at preventing the disease. </p></div></div><div class="article-content__item"><div class="article-tagged-profiles"><h2 class="article-tagged-profiles__title">Featured in this article</h2><div class="profile-list"><ul class="profile-list__item-container"><li class="profile-list__item profile-list__item--type--profile-list profile-list__item--size-mode--large profile-list__item--with-first-item-top-border"><div class="profile-detailed-info-list-item profile-detailed-info-list-item--link"><div class="profile-detailed-info-list-item__content-container"><a href="/center-clinical-investigation/profile/david-hafler/" aria-label="David A. Hafler" class="profile-detailed-info-list-item__content"><div class="profile-detailed-info-list-item__thumbnail-wrapper"><span class="" style="display:inline-block"></span></div><div class="profile-detailed-info-list-item__info"><span class="profile-detailed-info-list-item__name">David A. Hafler, MD, FANA</span><div class="LinesEllipsis text-overflow profile-detailed-info-list-item__title">William S. and Lois Stiles Edgerly Professor of Neurology and Professor of Immunobiology; Chair, Neurology; Neurologist-in-Chief, Yale New Haven Hospital<wbr/></div></div></a></div></div></li><li class="profile-list__item profile-list__item--type--profile-list profile-list__item--size-mode--large profile-list__item--with-first-item-top-border"><div class="profile-detailed-info-list-item profile-detailed-info-list-item--link"><div class="profile-detailed-info-list-item__content-container"><a href="/center-clinical-investigation/profile/sreeganga-chandra/" aria-label="Sreeganga Chandra" class="profile-detailed-info-list-item__content"><div class="profile-detailed-info-list-item__thumbnail-wrapper"><span class="" style="display:inline-block"></span></div><div class="profile-detailed-info-list-item__info"><span class="profile-detailed-info-list-item__name">Sreeganga Chandra, PhD</span><div class="LinesEllipsis text-overflow profile-detailed-info-list-item__title">Professor of Neurology & Neuroscience<wbr/></div></div></a></div></div></li><li class="profile-list__item profile-list__item--type--profile-list profile-list__item--size-mode--large profile-list__item--with-first-item-top-border"><div class="profile-detailed-info-list-item profile-detailed-info-list-item--link"><div class="profile-detailed-info-list-item__content-container"><a href="/center-clinical-investigation/profile/le-zhang/" aria-label="Le Zhang" class="profile-detailed-info-list-item__content"><div class="profile-detailed-info-list-item__thumbnail-wrapper"><span class="" style="display:inline-block"></span></div><div class="profile-detailed-info-list-item__info"><span class="profile-detailed-info-list-item__name">Le Zhang, PhD</span><div class="LinesEllipsis text-overflow profile-detailed-info-list-item__title">Assistant Professor of Neurology and of Neuroscience<wbr/></div></div></a></div></div></li></ul></div></div></div></div></article></section></div></div><div class="sidebar page__sidebar-container"><div class="sidebar__sticky-container"><div class="component-wrapper component-wrapper--all"></div></div></div></main><footer class="footer"><div class="footer__primary-panel-wrapper footer__primary-panel-wrapper--full-height"><div class="footer__content-container"><section class="footer__primary-panel" aria-label="Primary Links"><div class="desktop-footer-primary-panel"><div class="desktop-footer-primary-panel__organization-info-wrapper"><div class="footer-organization-info" role="presentation" aria-hidden="true"><svg xmlns="http://www.w3.org/2000/svg" aria-label="Yale School of Medicine" viewBox="0 0 384.2 29.1" focusable="false" class="site-wordmark__icon site-wordmark__icon--mode-ysm footer-organization-info__icon"><desc>Yale School of Medicine</desc><path d="m22.3 6.1-6.8 11.5v7.7c.8 1.9 2.8 2.1 4.7 2.2v1.1H6.8v-1.1c1.9-.1 4.2-.4 4.8-1.6v-8l-7-11.8C3.5 4.2 2.3 3.5 0 3.4V2.3h11.6v1.1c-2.2.1-2.9.5-3.5 1l6.5 11.2 6.3-11.1c-.7-.5-1.5-1-3.7-1.1V2.3h9.9v1.1c-2.2 0-3.6.8-4.8 2.7M35.9 29c-2.2 0-3.3-1.5-3.4-2.6-1.4 1.5-3.2 2.6-5 2.6-2.2 0-4.1-1.4-4.1-3.7 0-1.2.3-2.4.9-3.3l8.2-3v-3.1c0-1.9-.9-3.6-2.7-3.6-1.1 0-2.2 1.4-2.3 3.5l-3.7.6V16c1.2-3.7 5.3-5.2 7.3-5.2 3.8 0 5.1 2 5.1 5.1l-.1 8.7c0 1.7.9 2.1 1.7 2.1.7 0 1.3-.4 2.1-1.2v1.2c-.9 1-2.5 2.3-4 2.3m-8.3-6.8c-.2.7-.3 1.2-.3 2.2 0 1.2.7 2.5 2.1 2.5 1.2 0 1.9-.4 3.1-1.3V20c-1.1.5-3.7 1.7-4.9 2.2m12.7 6.4v-1c1.9-.1 2.4-.5 2.7-1.2V5c0-1.4-.2-2-3.1-2.2v-.9L47.5 0l.2.7-1.2 1.5v24.2c.4.8 1.2 1.1 2.9 1.2v1zm19.1.4c-4.3 0-7.7-3.4-7.7-8.2 0-5.9 3.6-9.9 8.7-9.9 4.1 0 6.4 2.3 6.4 6v.7l-11.2-.1c-.1.5-.1 1.2-.1 2.1 0 4.2 2.7 7 6.2 7 2.1 0 3.2-.7 4.8-2.2l.6 1c-2.4 2.1-4.3 3.6-7.7 3.6m.4-16.9c-2.1 0-3.5 1.7-4 4.3l7.3-.1c-.1-2.2-1.4-4.2-3.3-4.2M83.4 29.1c-2.1 0-3.8-.6-4.9-1l-.5-4.4h.7c.2 1.1 1 2.5 2 3.2.6.5 1.9 1.2 3 1.2 2.2 0 3.3-1.4 3.3-2.8 0-1.9-1.2-2.4-3.2-3.2-3.8-1.6-5.2-2.6-5.2-5.2 0-2.9 2.9-4.8 6.7-4.8 1.8 0 3.2.5 4.1.9v4.3h-.7c-.1-1.1-.5-2.5-1.5-3.1-.4-.2-1.4-.9-2.6-.9-2.1 0-3.2 1.3-3.2 2.6 0 1.7.9 2.4 3.5 3.4 3.5 1.4 5 2.5 5 5 0 2.9-2.9 4.8-6.5 4.8m25.1-1c-2 .6-2.6.9-5.7.9-5.3 0-9.2-3.8-9.2-8.7 0-5 4.1-8.4 9.2-8.4 2.6 0 4 .5 5.9.9v4.5h-.7c-.1-1.1-.6-2.4-1.5-3-.5-.3-1.7-1.3-3.9-1.3-3.7 0-5.8 3.1-5.8 6.7 0 4.8 2.7 8.2 7 8.2 1.4 0 2.4-.6 2.8-.9 1-.8 1.7-2 2-3.2l.8.1zm15.4.6V28c1.2 0 2.2-.4 2.5-.9V21h-8.8v6.1c.2.5 1.3.8 2.5.9v.7h-7.8V28c1.1 0 2.3-.4 2.5-.9V13.9c-.2-.5-1.3-.8-2.5-.9v-.7h7.8v.7c-1.1.1-2.3.4-2.5.9v5.7h8.8v-5.7c-.3-.5-1.3-.8-2.5-.9v-.7h7.9v.7c-1.2.1-2.2.4-2.5.9v13.2c.3.5 1.3.8 2.5.9v.7zm18.9.4c-5.2 0-8.2-3.6-8.2-8.5 0-5 4.2-8.6 9.3-8.6 5.3 0 8.2 3.6 8.2 8.4 0 5.1-4.1 8.7-9.3 8.7m-.3-16c-2.4 0-4.8 2.7-4.8 6.7 0 4.7 2.3 8.1 6.3 8.1 2.6 0 5-2.6 5-6.7 0-4.9-2.5-8.1-6.5-8.1m21.4 16c-5.2 0-8.2-3.6-8.2-8.5 0-5 4.2-8.6 9.3-8.6 5.3 0 8.2 3.6 8.2 8.4 0 5.1-4.1 8.7-9.3 8.7m-.3-16c-2.4 0-4.8 2.7-4.8 6.7 0 4.7 2.3 8.1 6.3 8.1 2.6 0 5-2.6 5-6.7 0-4.9-2.5-8.1-6.5-8.1m11.9 15.6V28c1-.1 2.6-.3 3-1.2V13.9c-.2-.5-1.3-.8-2.5-.9v-.7h8.1v.7c-1.1.1-2.5.4-2.7.9v13.5l4.7-.1c1.8 0 2.9-1.7 2.9-3.9h.7v5.3zm33 .4c-5.2 0-8.2-3.6-8.2-8.5 0-5 4.2-8.6 9.3-8.6 5.3 0 8.2 3.6 8.2 8.4.1 5.1-4.1 8.7-9.3 8.7m-.3-16c-2.4 0-4.8 2.7-4.8 6.7 0 4.7 2.3 8.1 6.3 8.1 2.6 0 5-2.6 5-6.7 0-4.9-2.5-8.1-6.5-8.1m24.4 3.4c-.1-2.3-1-2.9-3-2.9H226V20l3.5-.1c1.7-.1 2.4-.1 2.7-2h.7v5.5h-.7c-.2-2.1-.9-2.1-2.6-2.1h-3.5v5.5c.3.8 1.8 1.2 3 1.3v.7h-8.6V28c1.1-.1 2.4-.3 2.7-1.1V14c-.2-.6-1.4-.9-2.6-.9v-.7h10.7c.6 0 1.1 0 1.5-.2h.6v4.3zm26.2 12.2V28c1.2-.1 2.5-.4 2.7-.9l-.5-9.5v-2.7l-.8 2.1-5.2 11.7h-1l-4.5-12.3-.7-2-.1 1.8-.7 10.6c.2.5 1.4 1 2.6 1.1v.7h-6.7V28c1.2-.1 2.3-.6 2.6-1.1l.7-9.2c.1-.9.2-2.8.2-2.9V14c-.3-.4-1.1-.8-2.3-.9v-.7h5.8l.8 2.5 3.7 10.2 4.2-9.9 1.1-2.7h5.2v.5c-1.2.1-2.1.4-2.3.8v.6c0 .3.1 2.3.2 3.1l.5 9.5c.3.5 1.4.8 2.5.9v.7h-8zm16.5 0-5.8.1v-.7c1.2-.1 2.9-.4 3.3-1.2v-13c-.2-.5-1.3-.8-2.5-.9v-.7H281c.7 0 1.2-.1 1.5-.2h.6v4.3h-.7c-.1-2.3-1-2.9-3-2.9h-3.7v6.1h3.5c1.8 0 2.5 0 2.7-1.9h.6V23h-.7c-.2-2.1-.8-2.1-2.7-2.1h-3.5v5.6c.1.3.2.7.7.9l4.1-.1c1.7 0 2.9-.8 2.9-3h.6v4.3h-8.6zm20.8 0h-8.6V28c1.1 0 2.4-.4 2.6-.9V13.9c-.2-.5-1.5-.8-2.7-.9v-.7c3-.1 5.9-.3 8.2-.3 5.9 0 9.4 3 9.4 8s-3.9 8.8-8.9 8.7M294.5 13H293v13.9c.3.4 1.7.8 2.7.8 4.1 0 6.1-2.8 6.1-6.8 0-5.3-2.8-7.9-7.3-7.9m13.1 15.7V28c1.2-.1 2.4-.4 2.6-.9V13.9c-.2-.5-1.4-.8-2.6-.9v-.7h8.2v.7c-1.2.1-2.4.4-2.6.9V27c.2.5 1.4.8 2.6.9v.7h-8.2zm25.6-.6c-2 .6-2.6.9-5.7.9-5.3 0-9.2-3.8-9.2-8.7 0-5 4.1-8.4 9.2-8.4 2.6 0 4 .5 5.9.9v4.5h-.7c-.1-1.1-.6-2.4-1.5-3-.5-.3-1.7-1.3-3.9-1.3-3.7 0-5.8 3.1-5.8 6.7 0 4.8 2.7 8.2 7 8.2 1.4 0 2.4-.6 2.8-.9 1-.8 1.7-2 2-3.2l.8.1zm3.8.6V28c1.2-.1 2.4-.4 2.6-.9V13.9c-.2-.5-1.4-.8-2.6-.9v-.7h8.2v.7c-1.2.1-2.4.4-2.6.9V27c.2.5 1.4.8 2.6.9v.7H337zm27.8-14.5V24c0 1.4.1 3.7.2 4.9h-1.6l-10-12.3-1.1-1.7.1 1.5v5.9c0 1.4.1 3.4.2 4.5.2.5 1.7 1 2.9 1.1v.7h-7.1V28c1.2-.1 2.3-.6 2.5-1.1v-9.2c0-1.3 0-2.6-.1-3.5-.3-.5-1.3-1-2.5-1.1v-.7h5.2l1.5 1.9 8.4 10.3v-5.9c0-1.4-.1-3.6-.1-4.4-.2-.5-1.7-1.1-2.9-1.1v-.7h7.1v.5c-1.3.1-2.4.6-2.7 1.2m10.7 14.5-5.8.1v-.7c1.2-.1 2.9-.4 3.3-1.2v-13c-.2-.5-1.3-.8-2.5-.9v-.7h10.7c.7 0 1.2-.1 1.5-.2h.6v4.3h-.7c-.1-2.3-1-2.9-3-2.9h-3.7v6.1h3.5c1.8 0 2.5 0 2.7-1.9h.6V23h-.7c-.2-2.1-.8-2.1-2.7-2.1h-3.5v5.6c.1.3.2.7.7.9l4.1-.1c1.7 0 2.9-.8 2.9-3h.6v4.3h-8.6z"></path></svg></div></div><div class="desktop-footer-primary-panel__primary-links-wrapper"><nav aria-label="Footer Primary Links"><ul class="footer-primary-sections-list"><li class="footer-primary-sections-list__item"><div class="footer-section addresses-footer-section"><div class="footer-primary-link__content"><section class="addresses-footer-section__addresses-container addresses-footer-section__addresses-container--single-address" aria-label="Organization Address"><address class="addresses-footer-section__address-item"><div class="addresses-footer-section__address-line">Yale Center for Clinical Investigation</div><div class="addresses-footer-section__address-line">2 Church Street South</div><div class="addresses-footer-section__address-line">New Haven, CT 06519</div></address></section></div><div class="footer-primary-link__button-link"><a href="https://medicine.yale.edu/maps/" tabindex="0" class="button button--large button--primary button--color-mode--blue button--link button-with-icon" aria-label="Maps & Directions"><span class="button__label">Maps & Directions</span><span class="button__icon" aria-hidden="true"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="footer-primary-link__button-link-icon"><circle cx="12" cy="12" r="11.5" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></circle><path d="M11.352 18.758a.35.35 0 0 1-.66-.162v-4.938a.35.35 0 0 0-.35-.35H5.4a.35.35 0 0 1-.162-.66l11.751-6.109a.35.35 0 0 1 .472.472Z" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></span></a></div></div></li><li class="footer-primary-sections-list__item"><div class="footer-section footer-section--no-data calendar-footer-section"><div class="footer-primary-link__button-link"><a href="https://medicine.yale.edu/calendar/" tabindex="0" class="button button--large button--primary button--color-mode--blue button--link button-with-icon" aria-label="Calendar"><span class="button__label">Calendar</span><span class="button__icon" aria-hidden="true"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="footer-primary-link__button-link-icon"><rect width="22.5" height="19.5" x="0.75" y="3.75" rx="1.5" ry="1.5" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round;stroke-width:1.5px"></rect><path d="M.75 9.75h22.5M6.75 6V.75M17.25 6V.75M5.625 13.5a.375.375 0 1 0 .375.375.375.375 0 0 0-.375-.375M5.625 18.75a.375.375 0 1 0 .375.375.375.375 0 0 0-.375-.375M12 13.5a.375.375 0 1 0 .375.375A.375.375 0 0 0 12 13.5M12 18.75a.375.375 0 1 0 .375.375.375.375 0 0 0-.375-.375M18.375 13.5a.375.375 0 1 0 .375.375.375.375 0 0 0-.375-.375M18.375 18.75a.375.375 0 1 0 .375.375.375.375 0 0 0-.375-.375" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round;stroke-width:1.5px"></path></svg></span></a></div></div></li><li class="footer-primary-sections-list__item"><div class="footer-section social-media-footer-section"><div class="footer-primary-link__content"><ul class="social-media-footer-section__links-list"><li class="social-media-footer-section__link-list-item"><a href="https://facebook.com/yalediscovers" class="social-media-footer-section__link" aria-label="facebook"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="social-media-footer-section__link-icon"><path d="M17.768 7.5H13.5V5.6a.972.972 0 0 1 1.012-1.1c.418 0 2.988.01 2.988.01V.5h-4.329C9.244.5 8.5 3.474 8.5 5.355V7.5h-3v4h3v12h5v-12h3.851Z" style="fill:currentColor;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></a></li><li class="social-media-footer-section__link-list-item"><a href="https://twitter.com/yalediscovers" class="social-media-footer-section__link" aria-label="x"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="social-media-footer-section__link-icon"><path d="M17.294 22.475 1.454 1.453h5.252l15.84 21.022zm4.508-21.022-8.35 8.954M2.198 22.475l8.344-8.948" style="fill:none;stroke:currentColor;stroke-width:1.5;stroke-linecap:round;stroke-linejoin:round"></path></svg></a></li><li class="social-media-footer-section__link-list-item"><a href="https://instagram.com/yalediscovers" class="social-media-footer-section__link" aria-label="instagram"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="social-media-footer-section__link-icon"><rect width="23" height="23" x="0.5" y="0.5" rx="6" ry="6" style="fill:currentColor;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></rect><circle cx="12" cy="12" r="6"></circle><circle cx="19" cy="5" r="1.5"></circle></svg></a></li><li class="social-media-footer-section__link-list-item"><a href="https://www.youtube.com/user/yaleclinicalresearch" class="social-media-footer-section__link" aria-label="youtube"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="social-media-footer-section__link-icon"><path d="M23.5 6.939A3.44 3.44 0 0 0 20.062 3.5H3.937A3.44 3.44 0 0 0 .5 6.939v9.121a3.44 3.44 0 0 0 3.437 3.44h16.125a3.44 3.44 0 0 0 3.438-3.44Zm-14 8.5v-8.66l6.769 4.331Z" style="fill:currentColor;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></a></li><li class="social-media-footer-section__link-list-item"><a href="https://linkedin.com/groups/YCCI, Yale School of Medicine" class="social-media-footer-section__link" aria-label="linkedin"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="social-media-footer-section__link-icon"><path d="M6.5 22.5h-5v-13h5Zm9-9a2 2 0 0 0-2 2v7h-5v-13h5v1.485a6.3 6.3 0 0 1 3.99-1.495c2.962 0 5.01 2.2 5.01 6.355V22.5h-5v-7a2 2 0 0 0-2-2M6.5 5A2.5 2.5 0 1 1 4 2.5 2.5 2.5 0 0 1 6.5 5" style="fill:currentColor;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round"></path></svg></a></li></ul></div><div class="footer-primary-link__button-link"><a href="/ycci/about/contact/" tabindex="0" class="button button--large button--primary button--color-mode--blue button--link button-with-icon" aria-label="Contact Us"><span class="button__label">Contact Us</span><span class="button__icon" aria-hidden="true"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="footer-primary-link__button-link-icon"><rect width="22.5" height="15" x="0.75" y="4.5" rx="1.5" ry="1.5" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round;stroke-width:1.5px"></rect><path d="M15.687 9.975 19.5 13.5M8.313 9.975 4.5 13.5M22.88 5.014l-9.513 6.56a2.41 2.41 0 0 1-2.734 0L1.12 5.014" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round;stroke-width:1.5px"></path></svg></span></a></div></div></li></ul></nav></div></div></section></div></div><div class="footer__secondary-panel-wrapper"><div class="footer__content-container"><section class="footer__secondary-panel" aria-label="Secondary Links"><div class="footer__secondary-links"><nav class="footer-secondary-links-list" aria-label="Footer Secondary Links"><ul class="footer-secondary-links-list__list"><li class="footer-secondary-links-list__list-item"><a href="https://medicine.yale.edu/intranet/" class="footer-secondary-links-list__link" aria-label="Intranet">Intranet</a></li><li class="footer-secondary-links-list__list-item"><a href="mailto:ysm.editor@yale.edu" class="footer-secondary-links-list__link" aria-label="Site Editor">Site Editor</a></li><li class="footer-secondary-links-list__list-item"><a href="https://medicine.yale.edu/accessibility/" class="footer-secondary-links-list__link" aria-label="Accessibility at YSM">Accessibility at YSM</a></li><li class="footer-secondary-links-list__list-item"><a href="https://medicine.yale.edu/myysm/personal-resources/diversity-equity-inclusion/" class="footer-secondary-links-list__link" aria-label="Nondiscrimination & Title IX">Nondiscrimination & Title IX</a></li><li class="footer-secondary-links-list__list-item"><a href="https://medicine.yale.edu/myysm/personal-resources/safety-security-resources/" class="footer-secondary-links-list__link" aria-label="Safety & Security">Safety & Security</a></li><li class="footer-secondary-links-list__list-item"><a href="/privacy" class="footer-secondary-links-list__link" aria-label="Terms & Privacy Statement">Terms & Privacy Statement</a></li><li class="footer-secondary-links-list__list-item"><a href="https://yale.edu" class="footer-secondary-links-list__link" aria-label="Yale University">Yale University</a></li><li class="footer-secondary-links-list__list-item"><button type="button" class="footer-secondary-links-list__button" tabindex="0"><span>Manage Cookie Preferences</span></button></li></ul></nav></div><div class="footer__copyright-wrapper"><small class="footer-copyright">© <!-- -->2025<!-- --> <!-- -->Yale School of Medicine<!-- -->. Updated <!-- -->09/17/2024</small></div></section></div></div></footer></div><div class="back-to-top-button back-to-top-button--hidden back-to-top-button--without-touch" aria-hidden="true"><button type="button" aria-label="Back to top" class="back-to-top-button__button" tabindex="-1"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" focusable="false" class="back-to-top-button__arrow"><path d="M.75 17.189 11.47 6.47a.75.75 0 0 1 1.06 0l10.72 10.719" style="fill:none;stroke:currentColor;stroke-linecap:round;stroke-linejoin:round;stroke-width:1.5px;fill-rule:evenodd"></path></svg></button></div></div><div class="outdated-browser-warning" aria-hidden="true">Your browser is antiquated and no longer supported on this website. Please update your browser or switch to Chrome, Firefox or Safari. <br/>You can update your IE here: <br/><a class="outdated-browser-warning__link" href="https://support.microsoft.com/en-us/help/17621/internet-explorer-downloads">https://support.microsoft.com/en-us/help/17621/internet-explorer-downloads</a></div></div> <script id='page-data' type='application/json'>{"header":{"key":"DepartmentHeader","orderOnPage":-1,"model":{"departmentHomeLink":{"url":"/center-clinical-investigation","text":"Yale Center for Clinical Investigation"},"breadcrumbs":[{"url":"https://medicine.yale.edu/","text":"Yale School of Medicine"},{"url":"https://medicine.yale.edu/center-clinical-investigation/","text":"Yale Center for Clinical Investigation (YCCI)"}],"titleBackgroundColor":null,"isMarketingTemplate":false,"rootOrganizationType":"ysm","rootOrganizationLink":{"isCurrentLink":false,"rootOrganizationPrefix":"Ysm","currentLinkUrl":null,"url":"/ysm","text":"Yale School of Medicine"},"navigationItems":[{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/about","text":"About YCCI"},"subNavigationItems":[{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/about/mission","text":"Mission"},{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/about/tradition-of-discovery","text":"A Tradition of Discovery"},"subNavigationItems":[{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/about/tradition-of-discovery/history-of-firsts","text":"A History of Firsts"}],"hasCurrentLink":false},{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/about/collaboration","text":"Collaborations"},"subNavigationItems":[{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/about/collaboration/community-practices","text":"Collaborations with Community Practices"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/about/collaboration/fda","text":"Collaborations with the FDA"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/about/collaboration/other-institutions","text":"Collaborations with Other Institutions"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/about/collaboration/equitable-breakthroughs","text":"Equitable Breakthroughs in Medicine Development (EQBMED)"}],"hasCurrentLink":false},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/about/leadership","text":"Leadership & Faculty"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/about/job-opportunities","text":"Job Opportunities"}],"hasCurrentLink":false},{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services","text":"Research Services"},"subNavigationItems":[{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team","text":"Services by Team"},"subNavigationItems":[{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/protocol-design","text":"Protocol Design, Development & Feasibility"},"subNavigationItems":[{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/protocol-design/study-design-biostatistics","text":"Study Design, & Biostatistics"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/protocol-design/clinical-trials-project-management","text":"Clinical Trials Project Management"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/protocol-design/clinical-data-management","text":"Clinical Data Management"}],"hasCurrentLink":false},{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/protocol-activation","text":"Protocol Activation & Lifecycle Management"},"subNavigationItems":[{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/protocol-activation/coverage-analysis","text":"Coverage Analysis"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/protocol-activation/budget-financial-management","text":"Budget & Financial Management"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/protocol-activation/regulatory-process-support","text":"Regulatory Process Support"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/protocol-activation/oncore-protocol-subject-management","text":"OnCore Protocol & Subject Management"}],"hasCurrentLink":false},{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/operations","text":"Clinical Research Operations"},"subNavigationItems":[{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/operations/bionutrition-unit","text":"YNHH Bionutrition Unit"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/operations/clinical-services","text":"Clinical Services"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/operations/clinical-research-support-lab-services","text":"Clinical Research Support Lab Services"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/operations/investigational-drug-service","text":"YNHH Investigational Drug Service"},{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/operations/outpatient-inpatient-facilities","text":"Outpatient & Inpatient Facilities"},"subNavigationItems":[{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/operations/outpatient-inpatient-facilities/csru","text":"Church Street Research Unit (CSRU)"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/operations/outpatient-inpatient-facilities/wcru","text":"West Campus Research Unit (WCRU)"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/operations/outpatient-inpatient-facilities/mrrc","text":"Magnetic Resonance Research Center (MRRC)"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/operations/outpatient-inpatient-facilities/hru","text":"Hospital Research Unit (HRU)"}],"hasCurrentLink":false}],"hasCurrentLink":false},{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory","text":"QA, Compliance & Regulatory Affairs"},"subNavigationItems":[{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/clinicaltrials.gov-support-services","text":"Clinicaltrials.gov Support Services"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/clinical-research-billing-compliance","text":"Clinical Research Billing Compliance"},{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/ind-ide-support","text":"IND/IDE Support"},"subNavigationItems":[{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/ind-ide-support/ind-training","text":"IND Training"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/ind-ide-support/ide-training","text":"IDE Training"}],"hasCurrentLink":false},{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/quality-assurance-monitoring","text":"Quality Assurance & Monitoring"},"subNavigationItems":[{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/quality-assurance-monitoring/audit-preparedness","text":"Audit Preparedness"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/quality-assurance-monitoring/monitoring","text":"Monitoring"},{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/quality-assurance-monitoring/committees","text":"Committees"},"subNavigationItems":[{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/quality-assurance-monitoring/committees/data-and-safety-monitoring-committee","text":"Data and Safety Monitoring Committee (DSMC)"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/quality-assurance-monitoring/committees/pediatric-protocol-review-committee","text":"Pediatric Protocol Review Committee"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/qa-compliance-regulatory/quality-assurance-monitoring/committees/science-and-safety-committee","text":"Science and Safety Committee (SSC)"}],"hasCurrentLink":false}],"hasCurrentLink":false}],"hasCurrentLink":false},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/financial-services","text":"Clinical Research Finance"},{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/community-engagement-and-recruitment","text":"Community Engagement & Participant Recruitment"},"subNavigationItems":[{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/community-engagement-and-recruitment/engagement","text":"Community Engagement"},"subNavigationItems":[{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/community-engagement-and-recruitment/engagement/research","text":"Research in the Community"},"subNavigationItems":[{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/community-engagement-and-recruitment/engagement/research/cenr","text":"Community-Engaged Research (CEnR)"},{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/community-engagement-and-recruitment/engagement/research/cultural-ambassadors","text":"Cultural Ambassadors"},"subNavigationItems":[{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/community-engagement-and-recruitment/engagement/research/cultural-ambassadors/ame-zion-church","text":"African Methodist Episcopal (AME) Zion Church"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/community-engagement-and-recruitment/engagement/research/cultural-ambassadors/junta","text":"Junta for Progressive Action"}],"hasCurrentLink":false}],"hasCurrentLink":false}],"hasCurrentLink":false},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/services-by-team/community-engagement-and-recruitment/participant-recruitment","text":"Participant Recruitment"}],"hasCurrentLink":false}],"hasCurrentLink":false},{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/resources-documents","text":"Resources & Documents"},"subNavigationItems":[{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/resources-documents/training-documents","text":"Training Documents"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/resources-documents/training-videos","text":"Training Videos"}],"hasCurrentLink":false},{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/systems","text":"Systems & Infrastructure"},"subNavigationItems":[{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/systems/epic","text":"Epic (EHR)"},"subNavigationItems":[{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/systems/epic/epic-data-requests","text":"Epic Data Requests"}],"hasCurrentLink":false},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/systems/redcap","text":"REDCap"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/systems/ereg","text":"Advarra eREg"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/systems/hugo","text":"Hugo"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/systems/epic-care","text":"EpicCare (login)"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/systems/edc","text":"Advarra eSource + EDC"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/systems/evaluation","text":"Evaluation"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/research-services/systems/acrobat-sign","text":"Acrobat Sign"}],"hasCurrentLink":false}],"hasCurrentLink":false},{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/ctsa-funding","text":"CTSA & Funding"},"subNavigationItems":[{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/ctsa-funding/initiatives","text":"CTSA Initiatives"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/ctsa-funding/faculty-awards","text":"Scholar Awards for Junior Faculty"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/ctsa-funding/multidisciplinary-pre-doctoral-training-program","text":"Multidisciplinary Pre-Doctoral Training Program"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/ctsa-funding/multidisciplinary-post-doctoral-training-program","text":"Multidisciplinary Post-Doctoral Training Program"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/ctsa-funding/pilot-programs-awards","text":"Pilot Programs & Awards"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/ctsa-funding/milestones","text":"Milestones"}],"hasCurrentLink":false},{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education","text":"Workforce Development & Education"},"subNavigationItems":[{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/trainees","text":"Trainees"},"subNavigationItems":[{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/trainees/pre-doctoral","text":"Pre-Doctoral"},"subNavigationItems":[{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/trainees/pre-doctoral/awardees","text":"Awardees"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/trainees/pre-doctoral/faqs","text":"FAQ's"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/trainees/pre-doctoral/representative-publications","text":"Representative Publications"}],"hasCurrentLink":false},{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/trainees/post-doctoral","text":"Post Doctoral"},"subNavigationItems":[{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/trainees/post-doctoral/faqs","text":"FAQ's"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/trainees/post-doctoral/awardees","text":"Awardees"}],"hasCurrentLink":false}],"hasCurrentLink":false},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/clinical-research-staff-training","text":"Clinical Research Staff Training"},{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/internship-opportunities","text":"Internship Opportunities"},"subNavigationItems":[{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/internship-opportunities/exposures-program","text":"Exposures Program"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/internship-opportunities/post-baccalaureate-internship","text":"Post Baccalaureate Internship"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/internship-opportunities/summer-enrichment-research-experience","text":"Yale Summer Enrichment Research Experience"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/internship-opportunities/interns","text":"Past and Current YCCI Interns"}],"hasCurrentLink":false},{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/faculty","text":"Faculty"},"subNavigationItems":[{"topLink":{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/faculty/junior-faculty-scholars","text":"Jr Faculty Scholars"},"subNavigationItems":[{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/faculty/junior-faculty-scholars/scholars","text":"Current and Past Scholars"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/faculty/junior-faculty-scholars/representative-publications","text":"Representative Publications"}],"hasCurrentLink":false},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/faculty/phd-training","text":"PhD Training"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/faculty/mentoring","text":"Mentoring"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/workforce-development-education/faculty/team-science","text":"Team Science"}],"hasCurrentLink":false}],"hasCurrentLink":false},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"https://medicine.yale.edu/ycci/clinicaltrials/","text":"Find a Study"},{"isCurrentLink":false,"rootOrganizationPrefix":null,"currentLinkUrl":null,"url":"/center-clinical-investigation/news-events","text":"News & Events"}],"browseLinks":[{"url":"/ysm/about/","text":"About YSM"},{"url":"/ysm/faculty/","text":"Faculty"},{"url":"/ysm/myysm/","text":"Staff"},{"url":"/ysm/edu/","text":"Students"},{"url":"/ysm/edu/residency-fellowships/","text":"Residents & Fellows"},{"url":"https://yalemedicine.org","text":"Patients"},{"url":"/ysm/research/","text":"Researchers"},{"url":"/ysm/alumni/","text":"Alumni"}],"searchUrl":"/center-clinical-investigation/search/","ctaLink":null}},"footer":{"key":"Footer","orderOnPage":-1,"model":{"organizationType":"ysm","primarySections":[{"mailingAddresses":[{"id":3155,"officeName":null,"name":null,"addressLine1":"Yale Center for Clinical Investigation","addressLine2":"2 Church Street South","city":"New Haven","region":"CT","country":"United States","postalCode":"06519","category":null}],"link":{"url":"https://medicine.yale.edu/maps/","text":"Maps & Directions"}},{"eventsCount":0,"period":"2025-02-18T00:00:00Z","periodType":"month","link":{"url":"https://medicine.yale.edu/calendar/","text":"Calendar"}},{"socialMediaLinks":{"facebook":"https://facebook.com/yalediscovers","x":"https://twitter.com/yalediscovers","instagram":"https://instagram.com/yalediscovers","youtube":"https://www.youtube.com/user/yaleclinicalresearch","linkedin":"https://linkedin.com/groups/YCCI, Yale School of Medicine"},"link":{"url":"/ycci/about/contact/","text":"Contact Us"}}],"secondaryLinks":[{"url":"https://medicine.yale.edu/intranet/","text":"Intranet"},{"url":"mailto:ysm.editor@yale.edu","text":"Site Editor"},{"url":"https://medicine.yale.edu/accessibility/","text":"Accessibility at YSM"},{"url":"https://medicine.yale.edu/myysm/personal-resources/diversity-equity-inclusion/","text":"Nondiscrimination & Title IX"},{"url":"https://medicine.yale.edu/myysm/personal-resources/safety-security-resources/","text":"Safety & Security"},{"url":"/ysm/privacy","text":"Terms & Privacy Statement"},{"url":"https://yale.edu","text":"Yale University"}],"poweredByLink":{"url":"https://medicine.yale.edu/communications/","text":"Powered by Yale School of Medicine web platforms"},"lastModifiedDate":"2024-09-17T11:43:57.8799667Z"}},"pageSettings":{"hasContentOverlay":false,"hasCustomLayout":false,"isHomePage":false,"isHomePageLayout":false,"isDepartmentHeader":true,"showAnnouncementModal":false,"isWordPageVersion":false,"showEditPageSection":false,"useWideTemplate":false},"googleAdsSettings":null,"googleTagManagerSettings":{"id":"GTM-T29B2V8","isSpaTrackingEnabled":false},"freshpaintSettings":{"id":"b6b4bb12-e8a3-48f7-a8ed-aa0be94fb272","isEnabled":true},"facebookPixelSettings":{"id":null,"isEnabled":false},"trackersSettings":{"isMsClarityEnabled":true},"pageMetaData":{"socialMediaTitle":"Parkinson’s Disease Associated With Neuroinflammation in the Brain, New Analyses Reveal ","siteName":"Yale Center for Clinical Investigation","keywords":"","twitterAccountName":null,"twitterCardType":"summary","facebookAppId":"604142276782606","url":"https://medicine.yale.edu/center-clinical-investigation/news-article/parkinsons-disease-associated-with-neuroinflammation-in-the-brain-new-analyses-reveal/","resourceBaseUrl":"https://cdn1.medicine.yale.edu","faviconUrl":"https://cdn1.medicine.yale.edu/icons/ysm/favicon.ico","iconsFolderUrl":"https://cdn1.medicine.yale.edu/icons/ysm","webManifestFolderUrl":"https://cdn1.medicine.yale.edu/web-manifests/ysm","browserConfigFolderUrl":"https://cdn1.medicine.yale.edu/browser-configs/ysm","title":"Parkinson’s Disease Associated With Neuroinflammation in the Brain, New Analyses Reveal < Yale Center for Clinical Investigation","description":"Using single-cell transcriptomics and proteomics, Yale researchers have created a detailed cell atlas of brains affected by Parkinson’s disease.","imageMetaData":{"alt":"GettyImages-117099409040","width":1200,"height":630,"url":"https://ysm-res.cloudinary.com/image/upload/c_limit,f_auto,h_630,q_auto,w_1200/v1/yms/prod/91883f7d-73a9-41a4-9ea4-9ddb22f7d5bc","secureUrl":"https://ysm-res.cloudinary.com/image/upload/c_limit,f_auto,h_630,q_auto,w_1200/v1/yms/prod/91883f7d-73a9-41a4-9ea4-9ddb22f7d5bc"},"videoMetaData":null,"audioMetaData":null,"author":"Isabella Backman","pageType":"article","publishDate":"2024-11-07T05:00:00Z","canonicalUrl":"https://medicine.yale.edu/news-article/parkinsons-disease-associated-with-neuroinflammation-in-the-brain-new-analyses-reveal/","isNoIndex":true},"popularSearches":[],"pageStructuredData":[{"schemaName":"Article","jsonData":"{\"@type\":\"Article\",\"inLanguage\":\"en-US\",\"mainEntityOfPage\":{\"@type\":\"WebPage\",\"@id\":\"https://medicine.yale.edu/news-article/parkinsons-disease-associated-with-neuroinflammation-in-the-brain-new-analyses-reveal/\",\"@context\":\"http://schema.org\"},\"headline\":\"Parkinson’s Disease Associated With Neuroinflammation in the Brain, New Analyses Reveal \",\"url\":\"https://medicine.yale.edu/news-article/parkinsons-disease-associated-with-neuroinflammation-in-the-brain-new-analyses-reveal/\",\"Image\":{\"@type\":\"ImageObject\",\"url\":\"https://ysm-res.cloudinary.com/image/upload/c_limit,f_auto,h_630,q_auto,w_1200/v1/yms/prod/91883f7d-73a9-41a4-9ea4-9ddb22f7d5bc\",\"description\":\"GettyImages-117099409040\",\"height\":1200,\"width\":630,\"@context\":\"http://schema.org\"},\"dateCreated\":\"2024-11-07\",\"datePublished\":\"2024-11-07\",\"articleBody\":\"Using groundbreaking emerging sequencing technologies, Yale School of Medicine scientists are studying human brains impacted by Parkinson’s disease in unprecedented detail. This research is bringing them closer to understanding how the life-altering condition arises. In a recent study, the researchers generated a cell atlas—a comprehensive reference that maps out all cell types within an organ—based on postmortem human brains from individuals with late-stage disease. Using single cell transcriptomics and proteomics, which enabled them to measure gene and protein expression, they compared how their findings differed from that found in healthy controls. Their findings revealed key differences, including that brains affected by Parkinson’s disease have greater levels of neuroinflammation. The researchers also compared their Parkinson’s cell atlas to a previously published one that mapped cell types found in human brains affected by Alzheimer’s disease. They found that each disease has a distinct pathology that impacts the neurons differently but common signatures in glial cells and neuroinflammation. The researchers published their findings in Science Translational Medicine on October 30. The research was led by Le Zhang, PhD, assistant professor of neurology and of neuroscience, Sreeganga Chandra, PhD, associate professor of neurology and neuroscience, and David Hafler, MD, the William S. and Lois Stiles Edgerly Professor of Neurology and professor of immunobiology at Yale. “What we really want to do is learn how to prevent Parkinson’s disease,” says Hafler, who is also chair of Yale’s Department of Neurology. “This work in the brain is one more piece of the puzzle that suggests the importance of inflammation as a cause of the disease.” Parkinson’s disease is a progressive neurodegenerative disorder that impacts millions of people around the world. The condition is characterized by loss of neurons in the substantia nigra, a region in the midbrain that produces dopamine. It is also associated with the formation of Lewy bodies—abnormal clumps of protein that develop inside nerve cells in the brain. While Parkinson’s disease is primarily known for motor symptoms that result from the degeneration of dopamine-producing neurons, it also causes prefrontal cortex dysfunction. The prefrontal cortex is the region of the brain associated with complex cognitive functions such as decision-making, attention, and working memory. This region is also significantly impacted by Alzheimer’s disease. Parkinson’s disease is linked to greater levels of neuroinflammation Researchers have not had much insight into the underlying pathways that contribute to the onset and progression of Parkinson’s disease. Now, in their latest study, the Yale-led team ran multiple analyses on post-mortem tissue. By focusing their investigation on the prefrontal cortex, they were able to compare their analyses to previously reported data on Alzheimer’s disease. The team ran two major analyses: single-cell transcriptomics and proteomics. Through single-cell transcriptomics, they isolated the nuclei of the brain cells in the prefrontal cortex and sequenced all of the RNA, known as “the transcriptome.” Then, they compared differences in gene expression found in brains with Parkinson’s disease against healthy controls. Using the same tissue, they also ran a proteomics analysis, in which they used an analytical technique called mass spectrometry to measure protein expression in the tissues. This enabled the researchers to understand how the expression of proteins differs in Parkinson’s disease. “Our study helped us understand the gene changes in Parkinson’s disease at the cell type level,” says Zhang. “By integrating this with our proteomics data, we can better understand the effects of the disease at both RNA and protein levels.” The researchers found that brains with Parkinson’s disease showed signs of increased neuroinflammation, including elevated levels of two kinds of immune cells known as T cells and microglia. Furthermore, they found that the presence of Lewy bodies was inversely correlated to the expression of a class of proteins called chaperones—these enable other proteins to fold properly and prevent them from aggregating—in excitatory neurons that regulate electrical signals in the brain. This finding could have therapeutic implications, the authors say. “If we could increase chaperone capacity in the brain, we could potentially decrease the abnormal aggregation associated with Parkinson’s,” says Chandra. Next, the team looked for shared features between brains with Parkinson’s disease and Alzheimer’s disease. “We wanted to compare the two most common neurodegenerative diseases,” explains Zhang. To their surprise, they did not find any overlap in gene expression within neurons. This suggests that the diseases likely impact neurons in distinct ways, the researchers say. “Parkinson’s and Alzheimer’s are clinically different diseases that have different mechanisms, and therefore the options to treat them will be different,” says Chandra. Cell atlas will help guide future research The study gave researchers important insight into how Parkinson’s disease arises. “Before the advent of these technologies, we couldn’t interrogate human tissue to get insights into disease progression,” says Chandra. “These analyses will help inform our future experiments and are a platform to raise pertinent questions that we can test.” The team hopes their cell atlas will help guide the studies of research teams investigating Parkinson’s disease. In their own labs, the researchers’ next steps are to apply the same methods to brains in the early stages of the condition. In addition, they are looking at the blood and spinal fluid of patients, where they have also found signs of inflammation. Based on insights from these studies, the researchers plan to conduct clinical trials aimed at preventing the disease.\",\"author\":[{\"@type\":\"Person\",\"name\":\"Isabella Backman\",\"@context\":\"http://schema.org\"}],\"keywords\":[],\"publisher\":{\"@type\":\"NewsMediaOrganization\",\"name\":\"Yale School of Medicine\",\"foundingDate\":\"1810-10-15\",\"duns\":\"003036709\",\"url\":\"https://medicine.yale.edu\",\"logo\":{\"@type\":\"ImageObject\",\"url\":\"https://medicine.yale.edu/icons/ysm/largetile.png\",\"height\":310,\"width\":310,\"@context\":\"http://schema.org\"},\"sameAs\":[\"https://www.facebook.com/YaleSchoolOfMedicine\",\"https://twitter.com/YaleMed\",\"https://www.instagram.com/yaleschoolofmed/?hl=en\",\"https://www.linkedin.com/school/yale-university-school-of-medicine/\",\"https://www.youtube.com/user/YaleMedicine\",\"https://vimeo.com/user30675202\"],\"department\":\"Office of Communication\",\"parentOrganization\":{\"@type\":\"CollegeOrUniversity\",\"Name\":\"Yale University\",\"foundingDate\":\"1701\",\"duns\":\"043207562\",\"url\":\"https://www.yale.edu/\",\"address\":{\"@type\":\"PostalAddress\",\"addressCountry\":\"USA\",\"addressLocality\":\"New Haven\",\"addressRegion\":\"CT\",\"postalCode\":\"06520\",\"streetAddress\":\"333 Cedar Street\",\"@context\":\"http://schema.org\"},\"@context\":\"http://schema.org\"},\"@context\":\"http://schema.org\"},\"@context\":\"http://schema.org\"}"}],"cmsPageMetaData":{"id":13824,"lastPublishedDate":"2024-09-17T11:43:57.8799667Z","editPageUrl":"https://beatrix.yale.edu/cms/websites/626/pages/13824/content/edit"},"privacyCookiesUrl":"/ysm/privacy/#cookies","publicationUrl":"/center-clinical-investigation","topBanner":null,"mainComponents":[{"key":"NewsDetails","orderOnPage":1,"model":{"title":"Parkinson’s Disease Associated With Neuroinflammation in the Brain, New Analyses Reveal ","subTitle":null,"summary":"Using single-cell transcriptomics and proteomics, Yale researchers have created a detailed cell atlas of brains affected by Parkinson’s disease.","content":"<p>Using groundbreaking emerging sequencing technologies, Yale School of Medicine scientists are studying human brains impacted by Parkinson’s disease in unprecedented detail. This research is bringing them closer to understanding how the life-altering condition arises.</p> <p>In a recent study, the researchers generated a cell atlas—a comprehensive reference that maps out all cell types within an organ—based on postmortem human brains from individuals with late-stage disease. Using single cell transcriptomics and proteomics, which enabled them to measure gene and protein expression, they compared how their findings differed from that found in healthy controls. Their findings revealed key differences, including that brains affected by Parkinson’s disease have greater levels of neuroinflammation. </p> <p>The researchers also compared their Parkinson’s cell atlas to a previously published one that mapped cell types found in human brains affected by Alzheimer’s disease. They found that each disease has a distinct pathology that impacts the neurons differently but common signatures in glial cells and neuroinflammation. The researchers published their findings in <a href=\"https://www.science.org/doi/10.1126/scitranslmed.abo1997\"><em class=\"arx-italic-text\">Science Translational Medicine</em></a> on October 30.</p> <p>The research was led by <a href=\"https://medicine.yale.edu/profile/le-zhang/\">Le Zhang, PhD</a>, assistant professor of neurology and of neuroscience, <a href=\"https://medicine.yale.edu/profile/sreeganga-chandra/\">Sreeganga Chandra, PhD</a>, associate professor of neurology and neuroscience, and <a href=\"https://medicine.yale.edu/profile/david-hafler/\">David Hafler, MD</a>, the William S. and Lois Stiles Edgerly Professor of Neurology and professor of immunobiology at Yale.</p> <p>“What we really want to do is learn how to prevent Parkinson’s disease,” says Hafler, who is also chair of Yale’s Department of Neurology. “This work in the brain is one more piece of the puzzle that suggests the importance of inflammation as a cause of the disease.”</p> <p>Parkinson’s disease is a progressive neurodegenerative disorder that impacts millions of people around the world. The condition is characterized by loss of neurons in the substantia nigra, a region in the midbrain that produces dopamine. It is also associated with the formation of Lewy bodies—abnormal clumps of protein that develop inside nerve cells in the brain.</p> <p>While Parkinson’s disease is primarily known for motor symptoms that result from the degeneration of dopamine-producing neurons, it also causes prefrontal cortex dysfunction. The prefrontal cortex is the region of the brain associated with complex cognitive functions such as decision-making, attention, and working memory. This region is also significantly impacted by Alzheimer’s disease. </p> <h2>Parkinson’s disease is linked to greater levels of neuroinflammation</h2> <p>Researchers have not had much insight into the underlying pathways that contribute to the onset and progression of Parkinson’s disease. Now, in their latest study, the Yale-led team ran multiple analyses on post-mortem tissue. By focusing their investigation on the prefrontal cortex, they were able to compare their analyses to previously reported data on Alzheimer’s disease. </p> <p>The team ran two major analyses: single-cell transcriptomics and proteomics. Through single-cell transcriptomics, they isolated the nuclei of the brain cells in the prefrontal cortex and sequenced all of the RNA, known as “the transcriptome.” Then, they compared differences in gene expression found in brains with Parkinson’s disease against healthy controls. </p> <p>Using the same tissue, they also ran a proteomics analysis, in which they used an analytical technique called mass spectrometry to measure protein expression in the tissues. This enabled the researchers to understand how the expression of proteins differs in Parkinson’s disease. </p> <p>“Our study helped us understand the gene changes in Parkinson’s disease at the cell type level,” says Zhang. “By integrating this with our proteomics data, we can better understand the effects of the disease at both RNA and protein levels.”</p> <p>The researchers found that brains with Parkinson’s disease showed signs of increased neuroinflammation, including elevated levels of two kinds of immune cells known as T cells and microglia. </p> <p>Furthermore, they found that the presence of Lewy bodies was inversely correlated to the expression of a class of proteins called chaperones—these enable other proteins to fold properly and prevent them from aggregating—in excitatory neurons that regulate electrical signals in the brain. This finding could have therapeutic implications, the authors say. “If we could increase chaperone capacity in the brain, we could potentially decrease the abnormal aggregation associated with Parkinson’s,” says Chandra.</p> <p>Next, the team looked for shared features between brains with Parkinson’s disease and Alzheimer’s disease. “We wanted to compare the two most common neurodegenerative diseases,” explains Zhang. </p> <p>To their surprise, they did not find any overlap in gene expression within neurons. This suggests that the diseases likely impact neurons in distinct ways, the researchers say. “Parkinson’s and Alzheimer’s are clinically different diseases that have different mechanisms, and therefore the options to treat them will be different,” says Chandra. </p> <h2>Cell atlas will help guide future research</h2> <p>The study gave researchers important insight into how Parkinson’s disease arises. “Before the advent of these technologies, we couldn’t interrogate human tissue to get insights into disease progression,” says Chandra. “These analyses will help inform our future experiments and are a platform to raise pertinent questions that we can test.”</p> <p>The team hopes their cell atlas will help guide the studies of research teams investigating Parkinson’s disease. In their own labs, the researchers’ next steps are to apply the same methods to brains in the early stages of the condition. In addition, they are looking at the blood and spinal fluid of patients, where they have also found signs of inflammation. Based on insights from these studies, the researchers plan to conduct clinical trials aimed at preventing the disease. </p>","bylineDate":"2024-11-07T05:00:00Z","createdDate":"2024-11-07T00:00:00Z","submitter":"","sidebarTitle":null,"sidebarContent":null,"contact":null,"heroGallery":null,"galleries":[],"authors":[{"name":"Isabella Backman","url":"/center-clinical-investigation/profile/isabella-backman/#links-details-section"}],"tagLinks":[],"taggedProfiles":[{"id":69880,"name":"David A. Hafler","organizationName":null,"image":{"imageId":0,"url":"https://ysm-res.cloudinary.com/image/upload/v1/yms/prod/502e399a-f53b-4aa5-8ef9-ed5f561b8954","altText":"YSM3523_0693_David Hafler","width":6000,"height":4000,"imageVariants":[{"dimension":"Square","url":"https://ysm-res.cloudinary.com/image/upload/c_crop,x_474,y_28,w_1471,h_1471/v1/yms/prod/502e399a-f53b-4aa5-8ef9-ed5f561b8954","width":1471,"height":1471,"aspectRatio":"ratio1x1"},{"dimension":"Rectangle","url":"https://ysm-res.cloudinary.com/image/upload/c_crop,x_520,y_0,w_1405,h_1756/v1/yms/prod/502e399a-f53b-4aa5-8ef9-ed5f561b8954","width":1405,"height":1756,"aspectRatio":"ratio4x5"}]},"url":"/center-clinical-investigation/profile/david-hafler/","suffixes":{"familySuffix":null,"nonFamilySuffixes":["MD","FANA"]},"titles":["William S. and Lois Stiles Edgerly Professor of Neurology and Professor of Immunobiology","Chair, Neurology","Neurologist-in-Chief, Yale New Haven Hospital"],"disabled":false,"isYsphMember":false,"isExternal":false},{"id":66758,"name":"Sreeganga Chandra","organizationName":null,"image":{"imageId":0,"url":"https://ysm-res.cloudinary.com/image/upload/v1/yms/prod/8c3a9713-cbea-4cbb-a13e-1c8e7ddc0b46","altText":"SreegangaChandraProfile","width":1600,"height":2400,"imageVariants":[{"dimension":"Rectangle","url":"https://ysm-res.cloudinary.com/image/upload/v1/yms/prod/530b91d9-261d-4c97-a270-e70df9efd681","width":1600,"height":2000,"aspectRatio":"ratio4x5"},{"dimension":"Square","url":"https://ysm-res.cloudinary.com/image/upload/c_crop,x_97,y_190,w_1388,h_1388/v1/yms/prod/8c3a9713-cbea-4cbb-a13e-1c8e7ddc0b46","width":1388,"height":1388,"aspectRatio":"ratio1x1"},{"dimension":"Rectangle","url":"https://ysm-res.cloudinary.com/image/upload/c_crop,x_0,y_667,w_1600,h_1067/v1/yms/prod/8c3a9713-cbea-4cbb-a13e-1c8e7ddc0b46","width":1600,"height":1067,"aspectRatio":"ratio3x2"},{"dimension":"Rectangle","url":"https://ysm-res.cloudinary.com/image/upload/c_crop,x_0,y_900,w_1600,h_600/v1/yms/prod/8c3a9713-cbea-4cbb-a13e-1c8e7ddc0b46","width":1600,"height":600,"aspectRatio":"ratio8x3"}]},"url":"/center-clinical-investigation/profile/sreeganga-chandra/","suffixes":{"familySuffix":null,"nonFamilySuffixes":["PhD"]},"titles":["Professor of Neurology & Neuroscience"],"disabled":false,"isYsphMember":false,"isExternal":false},{"id":113341,"name":"Le Zhang","organizationName":null,"image":{"imageId":0,"url":"https://ysm-res.cloudinary.com/image/upload/v1/yms/prod/b7f0ff3e-7854-4f27-974a-119f684daba0","altText":"Le Zhang","width":1600,"height":2400,"imageVariants":[{"dimension":"Rectangle","url":"https://ysm-res.cloudinary.com/image/upload/c_crop,x_0,y_143,w_1600,h_2000/v1/yms/prod/b7f0ff3e-7854-4f27-974a-119f684daba0","width":1600,"height":2000,"aspectRatio":"ratio4x5"},{"dimension":"Square","url":"https://ysm-res.cloudinary.com/image/upload/c_crop,x_0,y_197,w_1600,h_1600/v1/yms/prod/b7f0ff3e-7854-4f27-974a-119f684daba0","width":1600,"height":1600,"aspectRatio":"ratio1x1"}]},"url":"/center-clinical-investigation/profile/le-zhang/","suffixes":{"familySuffix":null,"nonFamilySuffixes":["PhD"]},"titles":["Assistant Professor of Neurology and of Neuroscience"],"disabled":false,"isYsphMember":false,"isExternal":false}],"relatedLinks":[],"relatedDocumentLinks":[],"inlineMediaItems":[],"metaData":{"title":"Parkinson’s Disease Associated With Neuroinflammation in the Brain, New Analyses Reveal ","description":"Using single-cell transcriptomics and proteomics, Yale researchers have created a detailed cell atlas of brains affected by Parkinson’s disease.","imageMetaData":{"alt":"GettyImages-117099409040","width":1200,"height":630,"url":"https://ysm-res.cloudinary.com/image/upload/c_limit,f_auto,h_630,q_auto,w_1200/v1/yms/prod/91883f7d-73a9-41a4-9ea4-9ddb22f7d5bc","secureUrl":"https://ysm-res.cloudinary.com/image/upload/c_limit,f_auto,h_630,q_auto,w_1200/v1/yms/prod/91883f7d-73a9-41a4-9ea4-9ddb22f7d5bc"},"videoMetaData":null,"audioMetaData":null,"author":"Isabella Backman","pageType":"article","publishDate":"2024-11-07T05:00:00Z","canonicalUrl":"https://medicine.yale.edu/news-article/parkinsons-disease-associated-with-neuroinflammation-in-the-brain-new-analyses-reveal/","isNoIndex":true},"structuredData":[{"schemaName":"Article","jsonData":"{\"@type\":\"Article\",\"inLanguage\":\"en-US\",\"mainEntityOfPage\":{\"@type\":\"WebPage\",\"@id\":\"https://medicine.yale.edu/news-article/parkinsons-disease-associated-with-neuroinflammation-in-the-brain-new-analyses-reveal/\",\"@context\":\"http://schema.org\"},\"headline\":\"Parkinson’s Disease Associated With Neuroinflammation in the Brain, New Analyses Reveal \",\"url\":\"https://medicine.yale.edu/news-article/parkinsons-disease-associated-with-neuroinflammation-in-the-brain-new-analyses-reveal/\",\"Image\":{\"@type\":\"ImageObject\",\"url\":\"https://ysm-res.cloudinary.com/image/upload/c_limit,f_auto,h_630,q_auto,w_1200/v1/yms/prod/91883f7d-73a9-41a4-9ea4-9ddb22f7d5bc\",\"description\":\"GettyImages-117099409040\",\"height\":1200,\"width\":630,\"@context\":\"http://schema.org\"},\"dateCreated\":\"2024-11-07\",\"datePublished\":\"2024-11-07\",\"articleBody\":\"Using groundbreaking emerging sequencing technologies, Yale School of Medicine scientists are studying human brains impacted by Parkinson’s disease in unprecedented detail. This research is bringing them closer to understanding how the life-altering condition arises. In a recent study, the researchers generated a cell atlas—a comprehensive reference that maps out all cell types within an organ—based on postmortem human brains from individuals with late-stage disease. Using single cell transcriptomics and proteomics, which enabled them to measure gene and protein expression, they compared how their findings differed from that found in healthy controls. Their findings revealed key differences, including that brains affected by Parkinson’s disease have greater levels of neuroinflammation. The researchers also compared their Parkinson’s cell atlas to a previously published one that mapped cell types found in human brains affected by Alzheimer’s disease. They found that each disease has a distinct pathology that impacts the neurons differently but common signatures in glial cells and neuroinflammation. The researchers published their findings in Science Translational Medicine on October 30. The research was led by Le Zhang, PhD, assistant professor of neurology and of neuroscience, Sreeganga Chandra, PhD, associate professor of neurology and neuroscience, and David Hafler, MD, the William S. and Lois Stiles Edgerly Professor of Neurology and professor of immunobiology at Yale. “What we really want to do is learn how to prevent Parkinson’s disease,” says Hafler, who is also chair of Yale’s Department of Neurology. “This work in the brain is one more piece of the puzzle that suggests the importance of inflammation as a cause of the disease.” Parkinson’s disease is a progressive neurodegenerative disorder that impacts millions of people around the world. The condition is characterized by loss of neurons in the substantia nigra, a region in the midbrain that produces dopamine. It is also associated with the formation of Lewy bodies—abnormal clumps of protein that develop inside nerve cells in the brain. While Parkinson’s disease is primarily known for motor symptoms that result from the degeneration of dopamine-producing neurons, it also causes prefrontal cortex dysfunction. The prefrontal cortex is the region of the brain associated with complex cognitive functions such as decision-making, attention, and working memory. This region is also significantly impacted by Alzheimer’s disease. Parkinson’s disease is linked to greater levels of neuroinflammation Researchers have not had much insight into the underlying pathways that contribute to the onset and progression of Parkinson’s disease. Now, in their latest study, the Yale-led team ran multiple analyses on post-mortem tissue. By focusing their investigation on the prefrontal cortex, they were able to compare their analyses to previously reported data on Alzheimer’s disease. The team ran two major analyses: single-cell transcriptomics and proteomics. Through single-cell transcriptomics, they isolated the nuclei of the brain cells in the prefrontal cortex and sequenced all of the RNA, known as “the transcriptome.” Then, they compared differences in gene expression found in brains with Parkinson’s disease against healthy controls. Using the same tissue, they also ran a proteomics analysis, in which they used an analytical technique called mass spectrometry to measure protein expression in the tissues. This enabled the researchers to understand how the expression of proteins differs in Parkinson’s disease. “Our study helped us understand the gene changes in Parkinson’s disease at the cell type level,” says Zhang. “By integrating this with our proteomics data, we can better understand the effects of the disease at both RNA and protein levels.” The researchers found that brains with Parkinson’s disease showed signs of increased neuroinflammation, including elevated levels of two kinds of immune cells known as T cells and microglia. Furthermore, they found that the presence of Lewy bodies was inversely correlated to the expression of a class of proteins called chaperones—these enable other proteins to fold properly and prevent them from aggregating—in excitatory neurons that regulate electrical signals in the brain. This finding could have therapeutic implications, the authors say. “If we could increase chaperone capacity in the brain, we could potentially decrease the abnormal aggregation associated with Parkinson’s,” says Chandra. Next, the team looked for shared features between brains with Parkinson’s disease and Alzheimer’s disease. “We wanted to compare the two most common neurodegenerative diseases,” explains Zhang. To their surprise, they did not find any overlap in gene expression within neurons. This suggests that the diseases likely impact neurons in distinct ways, the researchers say. “Parkinson’s and Alzheimer’s are clinically different diseases that have different mechanisms, and therefore the options to treat them will be different,” says Chandra. Cell atlas will help guide future research The study gave researchers important insight into how Parkinson’s disease arises. “Before the advent of these technologies, we couldn’t interrogate human tissue to get insights into disease progression,” says Chandra. “These analyses will help inform our future experiments and are a platform to raise pertinent questions that we can test.” The team hopes their cell atlas will help guide the studies of research teams investigating Parkinson’s disease. In their own labs, the researchers’ next steps are to apply the same methods to brains in the early stages of the condition. In addition, they are looking at the blood and spinal fluid of patients, where they have also found signs of inflammation. Based on insights from these studies, the researchers plan to conduct clinical trials aimed at preventing the disease.\",\"author\":[{\"@type\":\"Person\",\"name\":\"Isabella Backman\",\"@context\":\"http://schema.org\"}],\"keywords\":[],\"publisher\":{\"@type\":\"NewsMediaOrganization\",\"name\":\"Yale School of Medicine\",\"foundingDate\":\"1810-10-15\",\"duns\":\"003036709\",\"url\":\"https://medicine.yale.edu\",\"logo\":{\"@type\":\"ImageObject\",\"url\":\"https://medicine.yale.edu/icons/ysm/largetile.png\",\"height\":310,\"width\":310,\"@context\":\"http://schema.org\"},\"sameAs\":[\"https://www.facebook.com/YaleSchoolOfMedicine\",\"https://twitter.com/YaleMed\",\"https://www.instagram.com/yaleschoolofmed/?hl=en\",\"https://www.linkedin.com/school/yale-university-school-of-medicine/\",\"https://www.youtube.com/user/YaleMedicine\",\"https://vimeo.com/user30675202\"],\"department\":\"Office of Communication\",\"parentOrganization\":{\"@type\":\"CollegeOrUniversity\",\"Name\":\"Yale University\",\"foundingDate\":\"1701\",\"duns\":\"043207562\",\"url\":\"https://www.yale.edu/\",\"address\":{\"@type\":\"PostalAddress\",\"addressCountry\":\"USA\",\"addressLocality\":\"New Haven\",\"addressRegion\":\"CT\",\"postalCode\":\"06520\",\"streetAddress\":\"333 Cedar Street\",\"@context\":\"http://schema.org\"},\"@context\":\"http://schema.org\"},\"@context\":\"http://schema.org\"},\"@context\":\"http://schema.org\"}"}],"cta":null,"relatedEvents":[]}}],"sidebarComponents":[{"key":"NewsDetailsSidebar","orderOnPage":2,"model":{"title":"Parkinson’s Disease Associated With Neuroinflammation in the Brain, New Analyses Reveal ","subTitle":null,"summary":"Using single-cell transcriptomics and proteomics, Yale researchers have created a detailed cell atlas of brains affected by Parkinson’s disease.","content":"<p>Using groundbreaking emerging sequencing technologies, Yale School of Medicine scientists are studying human brains impacted by Parkinson’s disease in unprecedented detail. This research is bringing them closer to understanding how the life-altering condition arises.</p> <p>In a recent study, the researchers generated a cell atlas—a comprehensive reference that maps out all cell types within an organ—based on postmortem human brains from individuals with late-stage disease. Using single cell transcriptomics and proteomics, which enabled them to measure gene and protein expression, they compared how their findings differed from that found in healthy controls. Their findings revealed key differences, including that brains affected by Parkinson’s disease have greater levels of neuroinflammation. </p> <p>The researchers also compared their Parkinson’s cell atlas to a previously published one that mapped cell types found in human brains affected by Alzheimer’s disease. They found that each disease has a distinct pathology that impacts the neurons differently but common signatures in glial cells and neuroinflammation. The researchers published their findings in <a href=\"https://www.science.org/doi/10.1126/scitranslmed.abo1997\"><em class=\"arx-italic-text\">Science Translational Medicine</em></a> on October 30.</p> <p>The research was led by <a href=\"https://medicine.yale.edu/profile/le-zhang/\">Le Zhang, PhD</a>, assistant professor of neurology and of neuroscience, <a href=\"https://medicine.yale.edu/profile/sreeganga-chandra/\">Sreeganga Chandra, PhD</a>, associate professor of neurology and neuroscience, and <a href=\"https://medicine.yale.edu/profile/david-hafler/\">David Hafler, MD</a>, the William S. and Lois Stiles Edgerly Professor of Neurology and professor of immunobiology at Yale.</p> <p>“What we really want to do is learn how to prevent Parkinson’s disease,” says Hafler, who is also chair of Yale’s Department of Neurology. “This work in the brain is one more piece of the puzzle that suggests the importance of inflammation as a cause of the disease.”</p> <p>Parkinson’s disease is a progressive neurodegenerative disorder that impacts millions of people around the world. The condition is characterized by loss of neurons in the substantia nigra, a region in the midbrain that produces dopamine. It is also associated with the formation of Lewy bodies—abnormal clumps of protein that develop inside nerve cells in the brain.</p> <p>While Parkinson’s disease is primarily known for motor symptoms that result from the degeneration of dopamine-producing neurons, it also causes prefrontal cortex dysfunction. The prefrontal cortex is the region of the brain associated with complex cognitive functions such as decision-making, attention, and working memory. This region is also significantly impacted by Alzheimer’s disease. </p> <h2>Parkinson’s disease is linked to greater levels of neuroinflammation</h2> <p>Researchers have not had much insight into the underlying pathways that contribute to the onset and progression of Parkinson’s disease. Now, in their latest study, the Yale-led team ran multiple analyses on post-mortem tissue. By focusing their investigation on the prefrontal cortex, they were able to compare their analyses to previously reported data on Alzheimer’s disease. </p> <p>The team ran two major analyses: single-cell transcriptomics and proteomics. Through single-cell transcriptomics, they isolated the nuclei of the brain cells in the prefrontal cortex and sequenced all of the RNA, known as “the transcriptome.” Then, they compared differences in gene expression found in brains with Parkinson’s disease against healthy controls. </p> <p>Using the same tissue, they also ran a proteomics analysis, in which they used an analytical technique called mass spectrometry to measure protein expression in the tissues. This enabled the researchers to understand how the expression of proteins differs in Parkinson’s disease. </p> <p>“Our study helped us understand the gene changes in Parkinson’s disease at the cell type level,” says Zhang. “By integrating this with our proteomics data, we can better understand the effects of the disease at both RNA and protein levels.”</p> <p>The researchers found that brains with Parkinson’s disease showed signs of increased neuroinflammation, including elevated levels of two kinds of immune cells known as T cells and microglia. </p> <p>Furthermore, they found that the presence of Lewy bodies was inversely correlated to the expression of a class of proteins called chaperones—these enable other proteins to fold properly and prevent them from aggregating—in excitatory neurons that regulate electrical signals in the brain. This finding could have therapeutic implications, the authors say. “If we could increase chaperone capacity in the brain, we could potentially decrease the abnormal aggregation associated with Parkinson’s,” says Chandra.</p> <p>Next, the team looked for shared features between brains with Parkinson’s disease and Alzheimer’s disease. “We wanted to compare the two most common neurodegenerative diseases,” explains Zhang. </p> <p>To their surprise, they did not find any overlap in gene expression within neurons. This suggests that the diseases likely impact neurons in distinct ways, the researchers say. “Parkinson’s and Alzheimer’s are clinically different diseases that have different mechanisms, and therefore the options to treat them will be different,” says Chandra. </p> <h2>Cell atlas will help guide future research</h2> <p>The study gave researchers important insight into how Parkinson’s disease arises. “Before the advent of these technologies, we couldn’t interrogate human tissue to get insights into disease progression,” says Chandra. “These analyses will help inform our future experiments and are a platform to raise pertinent questions that we can test.”</p> <p>The team hopes their cell atlas will help guide the studies of research teams investigating Parkinson’s disease. In their own labs, the researchers’ next steps are to apply the same methods to brains in the early stages of the condition. In addition, they are looking at the blood and spinal fluid of patients, where they have also found signs of inflammation. Based on insights from these studies, the researchers plan to conduct clinical trials aimed at preventing the disease. </p>","bylineDate":"2024-11-07T05:00:00Z","createdDate":"2024-11-07T00:00:00Z","submitter":"","sidebarTitle":null,"sidebarContent":null,"contact":null,"heroGallery":null,"galleries":[],"authors":[{"name":"Isabella Backman","url":"/center-clinical-investigation/profile/isabella-backman/#links-details-section"}],"tagLinks":[],"taggedProfiles":[{"id":69880,"name":"David A. Hafler","organizationName":null,"image":{"imageId":0,"url":"https://ysm-res.cloudinary.com/image/upload/v1/yms/prod/502e399a-f53b-4aa5-8ef9-ed5f561b8954","altText":"YSM3523_0693_David Hafler","width":6000,"height":4000,"imageVariants":[{"dimension":"Square","url":"https://ysm-res.cloudinary.com/image/upload/c_crop,x_474,y_28,w_1471,h_1471/v1/yms/prod/502e399a-f53b-4aa5-8ef9-ed5f561b8954","width":1471,"height":1471,"aspectRatio":"ratio1x1"},{"dimension":"Rectangle","url":"https://ysm-res.cloudinary.com/image/upload/c_crop,x_520,y_0,w_1405,h_1756/v1/yms/prod/502e399a-f53b-4aa5-8ef9-ed5f561b8954","width":1405,"height":1756,"aspectRatio":"ratio4x5"}]},"url":"/center-clinical-investigation/profile/david-hafler/","suffixes":{"familySuffix":null,"nonFamilySuffixes":["MD","FANA"]},"titles":["William S. and Lois Stiles Edgerly Professor of Neurology and Professor of Immunobiology","Chair, Neurology","Neurologist-in-Chief, Yale New Haven Hospital"],"disabled":false,"isYsphMember":false,"isExternal":false},{"id":66758,"name":"Sreeganga Chandra","organizationName":null,"image":{"imageId":0,"url":"https://ysm-res.cloudinary.com/image/upload/v1/yms/prod/8c3a9713-cbea-4cbb-a13e-1c8e7ddc0b46","altText":"SreegangaChandraProfile","width":1600,"height":2400,"imageVariants":[{"dimension":"Rectangle","url":"https://ysm-res.cloudinary.com/image/upload/v1/yms/prod/530b91d9-261d-4c97-a270-e70df9efd681","width":1600,"height":2000,"aspectRatio":"ratio4x5"},{"dimension":"Square","url":"https://ysm-res.cloudinary.com/image/upload/c_crop,x_97,y_190,w_1388,h_1388/v1/yms/prod/8c3a9713-cbea-4cbb-a13e-1c8e7ddc0b46","width":1388,"height":1388,"aspectRatio":"ratio1x1"},{"dimension":"Rectangle","url":"https://ysm-res.cloudinary.com/image/upload/c_crop,x_0,y_667,w_1600,h_1067/v1/yms/prod/8c3a9713-cbea-4cbb-a13e-1c8e7ddc0b46","width":1600,"height":1067,"aspectRatio":"ratio3x2"},{"dimension":"Rectangle","url":"https://ysm-res.cloudinary.com/image/upload/c_crop,x_0,y_900,w_1600,h_600/v1/yms/prod/8c3a9713-cbea-4cbb-a13e-1c8e7ddc0b46","width":1600,"height":600,"aspectRatio":"ratio8x3"}]},"url":"/center-clinical-investigation/profile/sreeganga-chandra/","suffixes":{"familySuffix":null,"nonFamilySuffixes":["PhD"]},"titles":["Professor of Neurology & Neuroscience"],"disabled":false,"isYsphMember":false,"isExternal":false},{"id":113341,"name":"Le Zhang","organizationName":null,"image":{"imageId":0,"url":"https://ysm-res.cloudinary.com/image/upload/v1/yms/prod/b7f0ff3e-7854-4f27-974a-119f684daba0","altText":"Le Zhang","width":1600,"height":2400,"imageVariants":[{"dimension":"Rectangle","url":"https://ysm-res.cloudinary.com/image/upload/c_crop,x_0,y_143,w_1600,h_2000/v1/yms/prod/b7f0ff3e-7854-4f27-974a-119f684daba0","width":1600,"height":2000,"aspectRatio":"ratio4x5"},{"dimension":"Square","url":"https://ysm-res.cloudinary.com/image/upload/c_crop,x_0,y_197,w_1600,h_1600/v1/yms/prod/b7f0ff3e-7854-4f27-974a-119f684daba0","width":1600,"height":1600,"aspectRatio":"ratio1x1"}]},"url":"/center-clinical-investigation/profile/le-zhang/","suffixes":{"familySuffix":null,"nonFamilySuffixes":["PhD"]},"titles":["Assistant Professor of Neurology and of Neuroscience"],"disabled":false,"isYsphMember":false,"isExternal":false}],"relatedLinks":[],"relatedDocumentLinks":[],"inlineMediaItems":[],"metaData":{"title":"Parkinson’s Disease Associated With Neuroinflammation in the Brain, New Analyses Reveal ","description":"Using single-cell transcriptomics and proteomics, Yale researchers have created a detailed cell atlas of brains affected by Parkinson’s disease.","imageMetaData":{"alt":"GettyImages-117099409040","width":1200,"height":630,"url":"https://ysm-res.cloudinary.com/image/upload/c_limit,f_auto,h_630,q_auto,w_1200/v1/yms/prod/91883f7d-73a9-41a4-9ea4-9ddb22f7d5bc","secureUrl":"https://ysm-res.cloudinary.com/image/upload/c_limit,f_auto,h_630,q_auto,w_1200/v1/yms/prod/91883f7d-73a9-41a4-9ea4-9ddb22f7d5bc"},"videoMetaData":null,"audioMetaData":null,"author":"Isabella Backman","pageType":"article","publishDate":"2024-11-07T05:00:00Z","canonicalUrl":"https://medicine.yale.edu/news-article/parkinsons-disease-associated-with-neuroinflammation-in-the-brain-new-analyses-reveal/","isNoIndex":true},"structuredData":[{"schemaName":"Article","jsonData":"{\"@type\":\"Article\",\"inLanguage\":\"en-US\",\"mainEntityOfPage\":{\"@type\":\"WebPage\",\"@id\":\"https://medicine.yale.edu/news-article/parkinsons-disease-associated-with-neuroinflammation-in-the-brain-new-analyses-reveal/\",\"@context\":\"http://schema.org\"},\"headline\":\"Parkinson’s Disease Associated With Neuroinflammation in the Brain, New Analyses Reveal \",\"url\":\"https://medicine.yale.edu/news-article/parkinsons-disease-associated-with-neuroinflammation-in-the-brain-new-analyses-reveal/\",\"Image\":{\"@type\":\"ImageObject\",\"url\":\"https://ysm-res.cloudinary.com/image/upload/c_limit,f_auto,h_630,q_auto,w_1200/v1/yms/prod/91883f7d-73a9-41a4-9ea4-9ddb22f7d5bc\",\"description\":\"GettyImages-117099409040\",\"height\":1200,\"width\":630,\"@context\":\"http://schema.org\"},\"dateCreated\":\"2024-11-07\",\"datePublished\":\"2024-11-07\",\"articleBody\":\"Using groundbreaking emerging sequencing technologies, Yale School of Medicine scientists are studying human brains impacted by Parkinson’s disease in unprecedented detail. This research is bringing them closer to understanding how the life-altering condition arises. In a recent study, the researchers generated a cell atlas—a comprehensive reference that maps out all cell types within an organ—based on postmortem human brains from individuals with late-stage disease. Using single cell transcriptomics and proteomics, which enabled them to measure gene and protein expression, they compared how their findings differed from that found in healthy controls. Their findings revealed key differences, including that brains affected by Parkinson’s disease have greater levels of neuroinflammation. The researchers also compared their Parkinson’s cell atlas to a previously published one that mapped cell types found in human brains affected by Alzheimer’s disease. They found that each disease has a distinct pathology that impacts the neurons differently but common signatures in glial cells and neuroinflammation. The researchers published their findings in Science Translational Medicine on October 30. The research was led by Le Zhang, PhD, assistant professor of neurology and of neuroscience, Sreeganga Chandra, PhD, associate professor of neurology and neuroscience, and David Hafler, MD, the William S. and Lois Stiles Edgerly Professor of Neurology and professor of immunobiology at Yale. “What we really want to do is learn how to prevent Parkinson’s disease,” says Hafler, who is also chair of Yale’s Department of Neurology. “This work in the brain is one more piece of the puzzle that suggests the importance of inflammation as a cause of the disease.” Parkinson’s disease is a progressive neurodegenerative disorder that impacts millions of people around the world. The condition is characterized by loss of neurons in the substantia nigra, a region in the midbrain that produces dopamine. It is also associated with the formation of Lewy bodies—abnormal clumps of protein that develop inside nerve cells in the brain. While Parkinson’s disease is primarily known for motor symptoms that result from the degeneration of dopamine-producing neurons, it also causes prefrontal cortex dysfunction. The prefrontal cortex is the region of the brain associated with complex cognitive functions such as decision-making, attention, and working memory. This region is also significantly impacted by Alzheimer’s disease. Parkinson’s disease is linked to greater levels of neuroinflammation Researchers have not had much insight into the underlying pathways that contribute to the onset and progression of Parkinson’s disease. Now, in their latest study, the Yale-led team ran multiple analyses on post-mortem tissue. By focusing their investigation on the prefrontal cortex, they were able to compare their analyses to previously reported data on Alzheimer’s disease. The team ran two major analyses: single-cell transcriptomics and proteomics. Through single-cell transcriptomics, they isolated the nuclei of the brain cells in the prefrontal cortex and sequenced all of the RNA, known as “the transcriptome.” Then, they compared differences in gene expression found in brains with Parkinson’s disease against healthy controls. Using the same tissue, they also ran a proteomics analysis, in which they used an analytical technique called mass spectrometry to measure protein expression in the tissues. This enabled the researchers to understand how the expression of proteins differs in Parkinson’s disease. “Our study helped us understand the gene changes in Parkinson’s disease at the cell type level,” says Zhang. “By integrating this with our proteomics data, we can better understand the effects of the disease at both RNA and protein levels.” The researchers found that brains with Parkinson’s disease showed signs of increased neuroinflammation, including elevated levels of two kinds of immune cells known as T cells and microglia. Furthermore, they found that the presence of Lewy bodies was inversely correlated to the expression of a class of proteins called chaperones—these enable other proteins to fold properly and prevent them from aggregating—in excitatory neurons that regulate electrical signals in the brain. This finding could have therapeutic implications, the authors say. “If we could increase chaperone capacity in the brain, we could potentially decrease the abnormal aggregation associated with Parkinson’s,” says Chandra. Next, the team looked for shared features between brains with Parkinson’s disease and Alzheimer’s disease. “We wanted to compare the two most common neurodegenerative diseases,” explains Zhang. To their surprise, they did not find any overlap in gene expression within neurons. This suggests that the diseases likely impact neurons in distinct ways, the researchers say. “Parkinson’s and Alzheimer’s are clinically different diseases that have different mechanisms, and therefore the options to treat them will be different,” says Chandra. Cell atlas will help guide future research The study gave researchers important insight into how Parkinson’s disease arises. “Before the advent of these technologies, we couldn’t interrogate human tissue to get insights into disease progression,” says Chandra. “These analyses will help inform our future experiments and are a platform to raise pertinent questions that we can test.” The team hopes their cell atlas will help guide the studies of research teams investigating Parkinson’s disease. In their own labs, the researchers’ next steps are to apply the same methods to brains in the early stages of the condition. In addition, they are looking at the blood and spinal fluid of patients, where they have also found signs of inflammation. Based on insights from these studies, the researchers plan to conduct clinical trials aimed at preventing the disease.\",\"author\":[{\"@type\":\"Person\",\"name\":\"Isabella Backman\",\"@context\":\"http://schema.org\"}],\"keywords\":[],\"publisher\":{\"@type\":\"NewsMediaOrganization\",\"name\":\"Yale School of Medicine\",\"foundingDate\":\"1810-10-15\",\"duns\":\"003036709\",\"url\":\"https://medicine.yale.edu\",\"logo\":{\"@type\":\"ImageObject\",\"url\":\"https://medicine.yale.edu/icons/ysm/largetile.png\",\"height\":310,\"width\":310,\"@context\":\"http://schema.org\"},\"sameAs\":[\"https://www.facebook.com/YaleSchoolOfMedicine\",\"https://twitter.com/YaleMed\",\"https://www.instagram.com/yaleschoolofmed/?hl=en\",\"https://www.linkedin.com/school/yale-university-school-of-medicine/\",\"https://www.youtube.com/user/YaleMedicine\",\"https://vimeo.com/user30675202\"],\"department\":\"Office of Communication\",\"parentOrganization\":{\"@type\":\"CollegeOrUniversity\",\"Name\":\"Yale University\",\"foundingDate\":\"1701\",\"duns\":\"043207562\",\"url\":\"https://www.yale.edu/\",\"address\":{\"@type\":\"PostalAddress\",\"addressCountry\":\"USA\",\"addressLocality\":\"New Haven\",\"addressRegion\":\"CT\",\"postalCode\":\"06520\",\"streetAddress\":\"333 Cedar Street\",\"@context\":\"http://schema.org\"},\"@context\":\"http://schema.org\"},\"@context\":\"http://schema.org\"},\"@context\":\"http://schema.org\"}"}],"cta":null,"relatedEvents":[]}}],"contextNavigation":null}</script> <script>window['applicationSettings'] = {"shouldShowSuppressedImageWarnings":false,"shouldShowBugReportButton":false,"shouldShowDownloadAsWordButton":false,"captchaKey":"a46dfca5-98da-4ec7-83e2-16980be648d0","facebookShareUrl":"https://www.facebook.com/dialog/share?app_id=604142276782606&display=popup&href=","isSearchFeedbackEnabled":true,"isSearchAnalyticsEnabled":true,"siteimproveScriptUrl":"https://siteimproveanalytics.com/js/siteanalyze_373.js","radarKey":"prj_live_pk_e9bc38cc9ac871b02332c0d599d7a893c03ad94d","mediaStatistics":{"baseUrl":"https://media-statistics-prod.ysmdevs.com","apiKey":"249c64e3-d0cc-45ed-97a0-5d3106411485","isEnabled":true}};</script> <noscript id="modern__LOADABLE_REQUIRED_CHUNKS__">[4589,7640,3688,7651,1578,186,6443,4480,6736,9819,6391,1739,5504,3053]</noscript><noscript id="modern__LOADABLE_REQUIRED_CHUNKS___ext">{"namedChunks":["modules-page-components-ComponentWrapper","modules-article-components-news-NewsDetails","modules-article-components-news-news-details-sidebar-NewsDetailsSidebar","modules-footer-components-Footer"]}</noscript> <script async data-chunk="main" src="https://cdn1.medicine.yale.edu/build/main.es2015.ff4738d7fae8cd594b64.js" type="module" crossorigin="anonymous"></script> <script async data-chunk="modules-article-components-news-NewsDetails" src="https://cdn1.medicine.yale.edu/build/4589.es2015.4c47bf8350b6c4f009a0.js" type="module" crossorigin="anonymous"></script> <script async data-chunk="modules-article-components-news-NewsDetails" src="https://cdn1.medicine.yale.edu/build/7640.es2015.305f7f9c55b908f8d7a2.js" type="module" crossorigin="anonymous"></script> <script async data-chunk="modules-article-components-news-NewsDetails" src="https://cdn1.medicine.yale.edu/build/3688.es2015.61379309f5274f4b1158.js" type="module" crossorigin="anonymous"></script> <script async data-chunk="modules-article-components-news-NewsDetails" src="https://cdn1.medicine.yale.edu/build/7651.es2015.df8b8aeaf41f78f2ec07.js" type="module" crossorigin="anonymous"></script> <script async data-chunk="modules-article-components-news-NewsDetails" src="https://cdn1.medicine.yale.edu/build/1578.es2015.dd71c3003a75394cf84a.js" type="module" crossorigin="anonymous"></script> <script async data-chunk="modules-article-components-news-NewsDetails" src="https://cdn1.medicine.yale.edu/build/186.es2015.18f4db14c8e5e4065c1f.js" type="module" crossorigin="anonymous"></script> <script async data-chunk="modules-article-components-news-news-details-sidebar-NewsDetailsSidebar" src="https://cdn1.medicine.yale.edu/build/6443.es2015.4890cbc400a8796edee4.js" type="module" crossorigin="anonymous"></script> <script async data-chunk="modules-article-components-news-news-details-sidebar-NewsDetailsSidebar" src="https://cdn1.medicine.yale.edu/build/4480.es2015.473ffd08eabb889a822c.js" type="module" crossorigin="anonymous"></script> <script async data-chunk="modules-article-components-news-news-details-sidebar-NewsDetailsSidebar" src="https://cdn1.medicine.yale.edu/build/6736.es2015.36fcc1e83004e7c6188d.js" type="module" crossorigin="anonymous"></script> <script async data-chunk="modules-article-components-news-news-details-sidebar-NewsDetailsSidebar" src="https://cdn1.medicine.yale.edu/build/9819.es2015.0646cda325bf5675c53b.js" type="module" crossorigin="anonymous"></script> <script async data-chunk="modules-article-components-news-news-details-sidebar-NewsDetailsSidebar" src="https://cdn1.medicine.yale.edu/build/6391.es2015.97db24b9904b8087c7f2.js" type="module" crossorigin="anonymous"></script> <script async data-chunk="modules-article-components-news-news-details-sidebar-NewsDetailsSidebar" src="https://cdn1.medicine.yale.edu/build/1739.es2015.57164941c596da5ad19e.js" type="module" crossorigin="anonymous"></script> <script async data-chunk="modules-article-components-news-news-details-sidebar-NewsDetailsSidebar" src="https://cdn1.medicine.yale.edu/build/5504.es2015.92e50a2dd82c1109ec41.js" type="module" crossorigin="anonymous"></script> <script async data-chunk="modules-footer-components-Footer" src="https://cdn1.medicine.yale.edu/build/3053.es2015.359573b73638d4069b34.js" type="module" crossorigin="anonymous"></script> <link rel="stylesheet" href="https://use.typekit.net/eqf4dwf.css" as="style" crossorigin> <!--<![endif]--> <script async type="text/plain" data-cookiecategory="analytics" src="https://siteimproveanalytics.com/js/siteanalyze_373.js"></script> </body> </html>