Complement and Inflammation Research

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<div class="layout layout--onecol"> <div class="layout__region layout__region--content"> <div class="block block-nhlbi-utils block-nhlbi-global-breadcrumb"> <div class="responsive-container responsive-container-constrained breadcrumbs-container"><div class="breadcrumbs"><ul> <li class='breadcrumb-home'><a href='/'>Home</a></li><li class='breacrumb-break'>/</li><li class='breadcrumb-parent'><a href='/node/80002'><span class='back-to'> < Back To </span>The Science</a></li><li class='breacrumb-break'>/</li><li class='breadcrumb-current'>Complement and Inflammation Research</li></ul></div></div> </div> <div class="block block-layout-builder block-extra-field-blocknodesciencecontent-moderation-control"> </div> </div> </div> <div class="layout layout--twocol-section layout--twocol-section--67-33 layout--twocol-component-lab-banner-section"> <div class="layout__region layout__region--first"> <div class="block block-layout-builder block-field-blocknodesciencefield-component-lab-banner"> <div class="field field--name-field-component-lab-banner field--type-entity-reference-revisions field--label-hidden field__item"> <div class="paragraph paragraph--type--component-lab-banner component-lab-banner responsive-container responsive-container-constrained paragraph--view-mode--default"> <div class="component-lab-banner-container"> <div class="component-lab-banner-title"> <h1>Complement and Inflammation Research</h1> </div> <div class="component-lab-banner-description"> <div class="field field--name-field-component-lab-banner-descr field--type-text-long field--label-hidden field__item"><p>The Laboratory for Complement and Inflammation Research, led by Dr. Claudia Kemper, aims to understand the unexpected roles of complement proteins in the regulation of key basic processes of the cell in health and disease.</p> </div> </div> <div class="component-lab-banner-links"> <span class="component-lab-banner-kicker">On This Page</span> <ul> </ul> </div> </div> </div> </div> </div> </div> <div class="layout__region layout__region--second"> <div class="block block-layout-builder block-field-blocknodesciencefield-component-lab-member-box"> <div class="field field--name-field-component-lab-member-box component-lab-member-box-container field__item"> <div class="component-lab-member-box-card"> <div class="component-lab-member-box-image"> <div class="field field--name-field-person-image field--type-image field--label-hidden field__item"> <img loading="lazy" src="/modules/custom/nhlbi_blazy/images/clear.png" width="200" height="200" alt="Claudia Kemper" data-src="/sites/default/files/styles/square_image/public/2017-12/Claudia%20Kemper.png?itok=aCem6eVl" class="b-lazy image-style-square-image" /> </div> </div> <article class="node node--type-nhlbi-person component-lab-member-box node--view-mode-component-lab-member-box"> <div class="node__content"> <div class="component-lab-member-box-top"> <div class="component-lab-member-box-name-row"> <div> <strong>Claudia Kemper, Ph.D.</strong> </div> </div> <div class="component-lab-member-box-role"> <div class="field field--name-field-employment-title field--type-string field--label-hidden field__item">Senior Investigator</div> </div> <div class="component-lab-member-box-links"> <div class="component-lab-member-box-email"> <i class="fas fa-envelope"></i><a href="mailto:claudia.kemper@nih.gov">Email</a> </div> </div> </div> <div class="component-lab-member-box-bottom"> <div class="component-lab-member-box-buttons"> <div class="component-lab-member-box-button nhlbi_button_secondary nhlbi_button_primary_blue_light"> <a href="#Meet-the-Team">Meet the Team</a> </div> <div class="component-lab-member-box-button-link"> <a href="#contact-the-lab">Contact us</a> </div> </div> </div> </div> </article> </div> </div> </div> </div> </div> <div class="layout layout--onecol"> <div class="layout__region layout__region--content"> <div class="block block-nhlbi-utils block-pi-research-interests component-pi-research-interests"> <div class="responsive-container responsive-container-constrained"> <h2 class="component-title">Senior Investigator Research Interests</h2> <div class="field field--name-field-research-interests field--type-text-long field--label-above"> <div class="field__label">Research Interests</div> <div class="field__item"><p>Our laboratory aims at understanding the unexpected roles of intracellularly active complement in the regulation of key basic processes of the cell in health and disease.</p><p>Complement is generally well appreciated as a serum-effective system and critical arm of innate immunity required for the detection and removal of invading pathogens. Work from Dr. Kemper's lab, however, has highlighted an equally profound impact of complement on adaptive immunity through direct regulation of CD4<sup>+</sup> T cells: signals mediated by T cell-expressed anaphylatoxin receptor C3aR and the complement regulator CD46 (which binds the complement activation fragment C3b) are critical checkpoints in human T cell lineage commitment and control initiation and resolution of inflammatory Th1 responses. Further, they have discovered that activation of the key complement components C3 and C5 is not confined to the extracellular space but occurs intracellulary (the ‘Complosome’) and that intracellular C3 and C5 activation fundamentally dictates the magnitude of Th1-mediated inflammation, the production of granzyme B and IFN-<span style="color:#222222;font-family:Symbol;font-size:12.0pt;mso-ansi-language:EN-US;mso-bidi-font-family:"Open Sans";mso-bidi-language:AR-SA;mso-fareast-font-family:Calibri;mso-fareast-language:EN-US;mso-fareast-theme-font:minor-latin;">g</span> by cytotoxic CD8+ T cells and the secretion of highly proinflammatory IL-1<span style="color:#222222;font-family:Symbol;font-size:12.0pt;mso-ansi-language:EN-US;mso-bidi-font-family:"Open Sans";mso-bidi-language:AR-SA;mso-fareast-font-family:Calibri;mso-fareast-language:EN-US;mso-fareast-theme-font:minor-latin;">b</span> by monocytes and macrophages. Consequently, perturbations in complosome activity in immune cells contributes majorly to a range of human disease states, including recurrent infections, autoimmunity (arthritis, SLE, CAPS, and scleroderma), chronic organ rejection, cancer, and cardiovascular disease.</p><p>Likely the most exciting recent development in their work is the observation that intracellular C3 and C5 are unexpected critical orchestrators of basic cellular processes, including the control of cell metabolism (induction of nutrient flux, glycolysis and oxidative phosphorylation), mitochondrial activity (directionality of the electron transport chain (ETC), impact on TCA cycle and ROS production) and gene transcription. Thus, CIRS has created a novel research area and propose that understanding the unexpected functions of the complosome will deliver critical new knowledge about cell biology in health and disease.</p><p>The central goal of Dr. Kemper's research programme is therefore to define the functional roles and regulative mechanisms of intracellular/autocrine complement and assess their biological relevance with an eye on delivering druggable targets in these pathways to therapeutically intervene in diseases (recently, the lab has broadened its interest heavily towards the role of the complosome in meningeal immunity and neurodegenerative disorders (such as MS)). To achieve this overarching goal, Dr. Kemper's lab are currently focusing on three key questions:</p><ol><li>What is the composition of the Complosome in different cells?</li><li>What are the functions of the Complosome?</li><li>How is the Complosome regulated?</li></ol><p>They utilize immune/tissue cells from healthy donors, from patients with complement deficiencies, from patients with immune cell-driven infectious, autoimmune disease or cancer and from patients with deviations in novel ‘complosome’-regulated pathways for gene and scRNA arrays, epigenetic landscape evaluation, and (spatial) proteomic and metabolomic assessments. This unbiased approach driven by human genetics and robust experimental in vitro systems will be combined with appropriate small animal (mouse) in vivo models to define biological significance of proteins/pathways discovered and to develop preclinical animal models for future pharmacological targeting. To achieve the latter, the Kemper lab is collaborating via a CRADA with Apellis Pharmaceuticals, Inc.</p></div> </div> </div> </div> </div> </div> <div class="layout layout--onecol"> <div class="layout__region layout__region--content"> <div class="block block-layout-builder block-field-blocknodesciencefield-science-related-pubs"> <div class="field field--name-field-science-related-pubs field--type-entity-reference field--label-above component-publications"> <div class="responsive-container responsive-container-constrained"> <h2 class="field__label">Featured Publications</h2> <div class='field__items'> <div class="field__item"> <article class="node node--type-publication node--view-mode-short-teaser"> <div class="singlePublicationCard"> <div class="flex-item"> <h3> <div class="field field--name-field-publication-title field--type-string-long field--label-hidden field__item">Intracellular complement activations sustains T cell homeostasis and mediates effector function.</div> </h3> <div class="publicationAuthors"> <span>Authors: </span>Liszewski, MK, Kolev, M, Le Friec, G, Leung, M, Bertram, PG, Fara, A, Subias, M, Pickering, MP, Drouet, C, Meri, S, Arstilla, TP, Pekkarinen, Ma, M, Cope, A, Reinheckel, T, Rodriguez de Cordoba, S, Afzali, B, Atkinson, JP, and Kemper, C. </div> <span> Immunity 2013 Jan 01</span>;39(6):1143-1157 </div> <div class="flex-item"> <a href="https://pubmed.ncbi.nlm.nih.gov/24315997/" aria-label="Intracellular complement activations sustains T cell homeostasis and mediates effector function." class="read-publications">Read Publication</a> </div> </div> </article> </div> <div class="field__item"> <article class="node node--type-publication node--view-mode-short-teaser"> <div class="singlePublicationCard"> <div class="flex-item"> <h3> <div class="field field--name-field-publication-title field--type-string-long field--label-hidden field__item">Complement mediates nutrient influx and metabolic reprogramming in Th1 responses.</div> </h3> <div class="publicationAuthors"> <span>Authors: </span>Kolev, M, Dimeloe, S, Le Friec, G, Arbore, G, Povoleri, GA, Fischer, M, Razik, L, Watson, J, Couzi, L, Afzali, B, Lavender, P, Hess, C, and Kemper, C. </div> <span> Immunity 2015 Jan 01</span>;42(6):1033-1047 </div> <div class="flex-item"> <a href="https://pubmed.ncbi.nlm.nih.gov/26084023/" aria-label="Complement mediates nutrient influx and metabolic reprogramming in Th1 responses." class="read-publications">Read Publication</a> </div> </div> </article> </div> <div class="field__item"> <article class="node node--type-publication node--view-mode-short-teaser"> <div class="singlePublicationCard"> <div class="flex-item"> <h3> <div class="field field--name-field-publication-title field--type-string-long field--label-hidden field__item">CD4+ T cell-intrinsic complement-NLRP3 inflammasome activity regulates IFN-g production</div> </h3> <div class="publicationAuthors"> <span>Authors: </span>Arbore, G, West EE, Spolski, R, Robertson, AB, Klos, A, Rheinheimer, C, Dutow, P, Woodruff, TM, O'Neill, LA, Coll, RC, Sher, A, Leonard, WJ, Monk, P, Cooper, MA, Arno, M, Afzali, B, Lachmann, HJ, Cope, AP, Mayer-Barber, K, and Kemper, C. </div> <span> Science 2016 Jan 01</span>;17(352):6292 </div> <div class="flex-item"> <a href="/node/130558" aria-label="CD4+ T cell-intrinsic complement-NLRP3 inflammasome activity regulates IFN-g production" class="read-publications">Read Publication</a> </div> </div> </article> </div> <div class="field__item"> <article class="node node--type-publication node--view-mode-short-teaser"> <div class="singlePublicationCard"> <div class="flex-item"> <h3> <div class="field field--name-field-publication-title field--type-string-long field--label-hidden field__item">Mitochondrial C5aR1 activity in macrophages controls IL-1β production underlying sterile inflammation.</div> </h3> <div class="publicationAuthors"> <span>Authors: </span>Niyonzima, N, Rahman, J, Kunz, N, ... Espevik, T, and Kemper, C. </div> <span> Sci Immunol 2021 Jan 01</span>;6(66): </div> <div class="flex-item"> <a href="https://pubmed.ncbi.nlm.nih.gov/34932384/" aria-label="Mitochondrial C5aR1 activity in macrophages controls IL-1β production underlying sterile inflammation." class="read-publications">Read Publication</a> </div> </div> </article> </div> </div> </div> </div> </div> </div> </div> <div class="layout layout--twocol-section layout--twocol-section--67-33"> <div class="layout__region layout__region--first"> <div class="block block-layout-builder block-field-blocknodesciencefield-senior-investigator"> <div class="field field--name-field-senior-investigator field--type-entity-reference field--label-hidden field__item"> <div class="component-senior-investigator responsive-container responsive-container-constrained"> <h2>Meet the Team</h2> <div class="meet-the-team"> <div class="block-senior-investigator-bg senior-bg-light-blue"> <div class="senior-image"> <div class="field field--name-field-person-image field--type-image field--label-hidden field__item"> <img loading="lazy" src="/modules/custom/nhlbi_blazy/images/clear.png" width="250" height="250" alt="Claudia Kemper" data-src="/sites/default/files/styles/square_image_250x250/public/2017-12/Claudia%20Kemper.png?itok=S859OdUU" class="b-lazy image-style-square-image-250x250" /> </div> </div> <div class="senior-info"> <h3 class="senior-name"> Claudia Kemper, Ph.D. </h3> <div class="senior-title"> <div class="field field--name-field-employment-title field--type-string field--label-hidden field__item">Senior Investigator</div> </div> <div class="senior-bio"> <div class="clearfix text-formatted field field--name-field-person-bio field--type-text-with-summary field--label-hidden field__item"><p>Dr. Kemper is a Senior Investigator and Section Chief at the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH) in Bethesda, Maryland.</p><p>Dr. Kemper received her Ph.D. in 1998 from the Bernhard-Nocht-Institute for Tropical Medicine, in Germany, and joined John Atkinson’s laboratory as a postdoctoral fellow at Washington University (Saint Louis) in 1999. Here, she discovered that the complement regulator CD46 is a key checkpoint in human Th1 induction. Dr. Kemper moved to King’s College London in 2008, where her group discovered the intracellularly active complement (the complosome) which serves non-canonical roles in cell biology, including the regulation of key metabolic pathways, mitochondrial dynamics, and gene transcription. Her group further showed that complosome perturbations are associated with a range of human diseases, including primary immune deficiency, and arthritic and cardiovascular disease.</p><p>Dr. Kemper is the recipient of a Wellcome Trust Investigator Award, the Merit Award for Excellence in Science from the International Complement Society, two Orloff Awards in Science from the NHLBI/NIH. She is an elected member of the Henry Kunkel Society, serves on the Scientific Board of Apellis, Inc., is the current NHLBI representative of the Women Scientists Advisors (WSA), a current member of the American Association of Immunologists (AA) Committee on the Status of Women, the Head of Admission of the NIH-OXCAM Scholars Program, and the sitting President of the International Complement Society.</p></div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="layout__region layout__region--second"> <div class="block block-layout-builder block-field-blocknodesciencefield-component-contact-lab"> <div class="field field--name-field-component-contact-lab field--type-entity-reference-revisions field--label-hidden field__item"> <div id="contact-the-lab" class="component-contact-lab"> <h3>Contact the lab</h3> <div class="component-contact-lab-content"> <div class="component-contact-lab-address"> <i class="fas fa-map-marker-alt"></i> <a href="http://maps.google.com/?q=10 Center Dr Bethesda, MD 20814 United States"> <div class="field field--name-field-lab-location field--type-address field--label-hidden field__item"><p class="address" translate="no"><span class="address-line1">10 Center Dr</span><br> <span class="locality">Bethesda</span>, <span class="administrative-area">MD</span> <span class="postal-code">20814</span><br> <span class="country">United States</span></p></div> </a> </div> <div class="component-contact-lab-phone-fax"> <i class="fas fa-phone-alt"></i> <div class="phone-fax-column"> <div class="component-contact-lab-phone"> <span>Phone: </span> <a href="tel:+1301-451-2872"> <div class="field field--name-field-phone-number field--type-string field--label-hidden field__item">301-451-2872</div> </a> </div> <div class="component-contact-lab-fax"><span>Fax: </span></div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="layout layout--onecol"> <div class="layout__region layout__region--content"> <div class="block block-layout-builder block-field-blocknodesciencefield-component-lab-members"> <div class="field field--name-field-component-lab-members field--type-entity-reference field--label-hidden page-theme-blue"> <div class="responsive-container responsive-container-constrained"> <div class="field__items"> <div class="field__item"> <article class="node node--type-nhlbi-person node--view-mode-lab-member-component"> <div class="profile-image"> <div class="field field--name-field-person-image field--type-image field--label-hidden field__item"> <img loading="lazy" src="/modules/custom/nhlbi_blazy/images/clear.png" width="200" height="200" alt="Rahman" data-src="/sites/default/files/styles/square_image/public/2021-09/Jubayer%20Rahman%20copy%202.jpg?itok=WJ5d35wP" class="b-lazy image-style-square-image" /> </div> </div> <h4> <strong>Muhammad Jubayer Rahman, Ph.D.</strong> </h4> <div class="node__content"> <div class="field field--name-field-employment-title field--type-string field--label-hidden 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contact-info"> <div class="contact-info-email"> <i class="fas fa-envelope"></i> <a href="mailto:westee2@mail.nih.gov" > westee2@mail.nih.gov </a> </div> </div> </article> </div> <div class="field__item"> <article class="node node--type-nhlbi-person node--view-mode-lab-member-component"> <div class="profile-image"> <div class="field field--name-field-person-image field--type-image field--label-hidden field__item"> <img loading="lazy" src="/modules/custom/nhlbi_blazy/images/clear.png" width="200" height="200" alt="Dr. Parul Singh" data-src="/sites/default/files/styles/square_image/public/2018-02/Parul%20Singh.jpg?itok=mV9Ykbfc" class="b-lazy image-style-square-image" /> </div> </div> <h4> <strong>Parul Singh, Ph.D.</strong> </h4> <div class="node__content"> <div class="field field--name-field-employment-title field--type-string field--label-hidden field__item">Postdoctoral Fellow</div> </div> <div class="node__content contact-info"> <div class="contact-info-email"> <i class="fas fa-envelope"></i> <a href="mailto:parul.singh@nih.gov" > parul.singh@nih.gov </a> </div> </div> </article> </div> <div class="field__item"> <article class="node node--type-nhlbi-person node--view-mode-lab-member-component"> <div class="profile-image"> <div class="field field--name-field-person-image field--type-image field--label-hidden field__item"> <img loading="lazy" src="/modules/custom/nhlbi_blazy/images/clear.png" width="200" height="200" alt="Natalia Kunz" data-src="/sites/default/files/styles/square_image/public/2018-11/Natalia%20Kunz4.jpg?itok=fjrwWAjZ" class="b-lazy image-style-square-image" /> </div> </div> <h4> <strong>Natalia Kunz, Ph.D.</strong> </h4> <div class="node__content"> <div class="field field--name-field-employment-title field--type-string field--label-hidden field__item">Postdoctoral Fellow</div> </div> <div class="node__content contact-info"> <div class="contact-info-email"> <i class="fas fa-envelope"></i> <a href="mailto:natalia.kunz@nih.gov" > natalia.kunz@nih.gov </a> </div> </div> </article> </div> <div class="field__item"> <article class="node node--type-nhlbi-person node--view-mode-lab-member-component"> <div class="profile-image"> <div class="field field--name-field-person-image field--type-image field--label-hidden field__item"> <img loading="lazy" src="/modules/custom/nhlbi_blazy/images/clear.png" width="200" height="200" alt="Nicolas Merles" data-src="/sites/default/files/styles/square_image/public/2018-10/Nicolas%20Merles1.jpeg?itok=kESspbR7" class="b-lazy image-style-square-image" /> </div> </div> <h4> <strong>Nicolas Merles, Ph.D.</strong> </h4> <div class="node__content"> <div class="field field--name-field-employment-title field--type-string field--label-hidden field__item">Postdoctoral Fellow</div> </div> </article> </div> <div class="field__item"> <article class="node node--type-nhlbi-person node--view-mode-lab-member-component"> <div class="profile-image"> <div class="field field--name-field-person-image field--type-image field--label-hidden field__item"> <img loading="lazy" src="/modules/custom/nhlbi_blazy/images/clear.png" width="200" height="200" alt="Jack Bibby" data-src="/sites/default/files/styles/square_image/public/2021-04/Jack%20Bibby_photo%5B1%5D%20copy.jpg?itok=ggMRAqbi" class="b-lazy image-style-square-image" /> </div> </div> <h4> <strong>Jack Bibby, Ph.D.</strong> </h4> <div class="node__content"> <div class="field field--name-field-employment-title field--type-string field--label-hidden field__item">Postdoctoral Fellow </div> </div> <div class="node__content contact-info"> <div class="contact-info-email"> <i class="fas fa-envelope"></i> <a href="mailto:jack.bibby@nih.gov" > jack.bibby@nih.gov </a> </div> </div> </article> </div> <div class="field__item"> <article class="node node--type-nhlbi-person node--view-mode-lab-member-component"> <div class="profile-image"> <div class="field field--name-field-person-image field--type-image field--label-hidden field__item"> <img 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width="200" height="200" alt="Adam F. Maleki, M.Sc., Ph.D." data-src="/sites/default/files/styles/square_image/public/2023-09/adam_maleki.jpg?itok=NfUqEIlx" class="b-lazy image-style-square-image" /> </div> </div> <h4> <strong>Adam F. 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