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Michael Steffen Kobor - Department of Medical Genetics

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<span class="trail-end">Michael Steffen Kobor</span></div><div class="expand row-fluid" role="main"> <div id="primary-secondary" class="sidebar aside span3"> <div id="primary"> </div><!-- #primary --> <div id="secondary"> </div><!-- #secondary --> </div><!-- #primary-secondary .aside --> <div id="content" class="hfeed content span9"> <div id="post-14041" class="hentry post publish post-1 odd author-azin-zeinali has-excerpt category-epigenetics-epigenomics-gene-regulation category-facultyprofiles category-genomics-bioinformatics category-pharmacogenomics category-professors category-research category-research-faculty"> <h1 class='post-title entry-title'>Michael Steffen Kobor</h1> <div class="entry-content"> <div class="name field-item full"> <div class="field-shell field-shell-name "> <div class="field" data-count="0"></div> </div> </div> <div class="email field-item two-third"> <div class="field-shell field-shell-email field-shell-multiple"> <p><a href="https://med-fom-medgen.sites.olt.ubc.ca/person/michael-kobor/"><strong>Dr. Michael Steffen Kobor, PhD</strong></a></p> <p>Edwin S.H. Leong UBC Chair in Healthy Aging &#8211; a UBC President’s Excellence Chair</p> <p>Tier 1 Canada Research Chair in Social Epigenetics</p> <p>Professor, Department of Medical Genetics, University of British Columbia</p> <p>Investigator, BCCHR</p> <p>Senior Scientist, Centre for Molecular Medicine and Therapeutics at BC Children’s Hospital Research Institute (BCCHR)</p> <p>Email: <a href="mailto:michael.kobor@ubc.ca">michael.kobor@ubc.ca</a></p> <p>Phone: 604-875-3803</p> <p>Site: <a href="https://bcchr.ca/kobor-lab">https://bcchr.ca/kobor-lab</a></p> <p>Assistant: Tanya Erb</p> <p>Assistant Phone: 604-875-2345 ext. 5901</p> <p>Mailing Address: Room A5-165, 950 West 28th Avenue, Vancouver BC V5Z 4H4</p> <p><strong>Overview</strong></p> <p>As the sole carrier of genetic information, DNA does not exist as a naked template in the eukaryotic genome; instead DNA exists as a chromatin structure amenable to the changing environment, especially during the sensitive period of childhood. Not surprisingly, many complex regulatory mechanisms act on chromatin to ensure that each cell expresses only the appropriate genes, duplicates its genome with high fidelity, divides only when required, and combats constant assaults on its DNA.</p> <p>Failure in any of the mechanisms regulating these events can lead to a wide range of outcomes from altered developmental trajectories to complex diseases. Furthermore, a number of chromatin modifying proteins are involved in genetic susceptibility to diseases. The objective of our research is to understand the <strong>molecular mechanisms of epigenetic regulation in response to the environment.</strong> This is largely achieved through evaluating DNA methylation, histone variants, post-translational modification of histones, and nucleosome positioning. Additionally, genetic variation may interact with specific environments, imparting sensitivity or resilience, to ultimately alter epigenetics patterns and phenotypic outcomes.</p> <p><strong>Project Overview</strong></p> <p>A major facet of our research program investigates how our social environments and life experiences get “under the skin” through biological embedding to influence health and behaviour across the life span. As world-leading experts in social epigenetics, my team has established a program of interdisciplinary research with the goal of translating foundational genetic discovery into interventions and policy change to promote healthy life trajectories. We regularly collaborate with leading scholars and elite universities around the world, bringing together experts in fields spanning molecular biology to anthropology and epidemiology, with a common purpose: to identify the epigenetic signatures of health and disease. This interdisciplinary team is focused on developing a “society to cell” paradigm for population health research – one that continues to challenge established ways of thinking about how and why some people live longer, healthier lives.</p> <p>Currently, as the inaugural Edwin S.H. Leong UBC Chair in Healthy Aging – a UBC President’s Excellence Chair, I am bringing together faculty, trainees, and research personnel across UBC and engaging experts at universities around the world in building UBC’s new comprehensive program of healthy aging research. The new Edwin S.H. Leong Healthy Aging Program aims to help us better understand what combination of genetics, environment, and lifestyle choices determine health and aging, and how we might effectively intervene at any stage of disease vulnerability or disease progression to redefine the aging experience and improve quality of life.</p> <p><strong>Selected Publications</strong></p> <p>Lu P.Y., Kirlin, A.C., Aristizaba, M.J., Brewis H.T., Lévesque N., Setiaputra D.T., Avvakumov N., Benschop J.J., Groot Koerkamp M., Holstege F.C., Krogan N.J., Yip C. K., Côté J., and Kobor M.S. (2022). A balancing act: Interactions within Nua4/tip60 regulate PICNUA4 function in saccharomyces cerevisiae and humans. Genetics. doi.org/10.1093/genetics/iyac136.</p> <p>Bergstedt J., Azzou,S., Tsuo K., Jaquaniello A., Urrutia A., Rotival M., Lin D.T.S, MacIsaac J.L., Kobor M.S., Albert M.L., Duffy D., Patin E., and Quintana-Murci, L.; Milieu Intérieur Consortium. (2021). The immune factors driving DNA methylation variation in human blood. Nat Commun. 13(1):5895. doi: 10.1038/s41467-022-33511-6..</p> <p>Brewis H.T., Wang A.Y., Gaub A., Lau J.J., Stirling P.C., and Kobor M.S. (2021). What makes a histone variant a variant: Changing H2A to become H2A.Z. PLOS Genetics, 17(12):e1009950. doi.org/10.1371/journal.pgen.1009950.</p> <p>McEwen L.M., O’Donnell K.J., McGill M.G., Edgar R.D., Jones M.J., MacIsaac J.L., Lin D.T.S., Ramadori K., Morin A., Gladish N., Garg E., Unternaehrer E., Pokhvisneva I., Karnani N., Kee M.Z.L., Klengel T., Adler N.E.,  Barr R.G., Letourneau N., Giesbrecht G.F, Reynolds J.N., Czamara D., Armstrong J.M., Essex M.J., de Weerth C., Beijers R., Tollenaar M.S., Bradley B., Jovanovic T., Ressler K.J., Steiner M., Entringer S., Wadhwa P.D., Buss C., Bush N.R., Binder E.B., Boyce W.T., Meaney M.J., Horvath S., and Kobor M.S. (2019). The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells. Proc Natl Acad Sci USA. 117(38):23329-23335. doi:10.1073/pnas.1820843116.</p> <p>Brown J.A.R., and  Kobor M.S. (2019). Budding yeast RTT107 prevents checkpoint hyperactivation after replicative stress by limiting DNA damage. DNA Repair. 74:1–16. doi.org/10.1016/j.dnarep.2019.01.001.</p> <p>Aristizabal M.J., Dever K., Negri G.L., Shen M., Hawe N., Benschop J.J., Holstege F.C.P., Krogan N. J., Sadowski I., and Kobor M.S. (2019). Regulation of SKN7-dependent, oxidative stress-induced genes by the RNA polymerase II-CTD phosphatase, FCP1, and mediator kinase subunit, CDK8, in yeast. J Biol Chem. 294(44):16080–16094. doi.org/10.1074/jbc.ra119.008515.</p> <p>Jones M.J., Moore S.R., and Kobor M.S. (2018). Principles and challenges of applying epigenetic epidemiology to psychology. Annu Rev Psychol. 69:459–485. doi.org/10.1146/annurev-psych-122414-033653.</p> <p>Austin M.K., Chen E., Ross K.M., McEwen L.M., Maclsaac J.L., Kobor M.S., and Miller G.E. (2018). Early-life socioeconomic disadvantage, not current, predicts accelerated epigenetic aging of monocytes. Psychoneuroendocrinology. 97:131–134. doi.org/10.1016/j.psyneuen.2018.07.007.</p> <p>Moore S.R., McEwen L.M., Quirt J., Morin A., Mah S.M., Barr R.G., Boyce W.T., and Kobor M.S. (2017). Epigenetic correlates of neonatal contact in humans. Dev Psychopathol. 29(5): 1517–1538. doi.org/10.1017/s0954579417001213.</p> <p>Clifford R.L., Jones M.J., MacIsaac J.L., McEwen L.M., Goodman S.J., Mostafavi S., Kobor M.S., and Carlsten C. (2017). Inhalation of diesel exhaust and allergen alters human bronchial epithelium DNA methylation. J Allergy Clin Immunol. 139(1):112–121. doi.org/10.1016/j.jaci.2016.03.046.</p> <p>Lu P.Y., and Kobor M.S. (2014). Maintenance of heterochromatin boundary and nucleosome composition at promoters by the ASF1 histone chaperone and SWR1-C chromatin remodeler in saccharomyces cerevisiae. Genetics. 197(1):133–145. doi.org/10.1534/genetics.114.162909.</p> <p>Aristizabal M.J., Negri G.L., Benschop J.J., Holstege F.C., Krogan N.J., and Kobor M.S. (2013). High-throughput genetic and gene expression analysis of the RNAPII-CTD reveals unexpected connections to srb10/CDK8. PLoS Genetics. 9(8):e1003758 doi.org/10.1371/journal.pgen.1003758.</p> <p>Wang A.Y., Aristizabal M.J., Ryan C., Krogan N.J., and Kobor M.S. (2011). Key functional regions in the histone variant H2A.Z C-terminal docking domain. Mol Cell Biol. 31(18):3871–3884. doi.org/10.1128/mcb.05182-11.</p> <p>Essex M.J., Boyce W.T., Hertzman C., Lam L.L., Armstrong J.M., Neumann S.M., and Kobor M.S. (2011). Epigenetic vestiges of early developmental adversity: Childhood stress exposure and DNA methylation in adolescence. Child Dev. 84(1):58–75. doi.org/10.1111/j.1467-8624.2011.01641.x</p> <p>Miller G.E., Chen E., Fok A.K., Walker H., Lim A., Nicholls E.F., Cole S., and Kobor M.S. (2009). Low early-life social class leaves a biological residue manifested by decreased glucocorticoid and increased proinflammatory signaling. Proc Natl Acad Sci USA. 106(34):14716–14721. doi.org/10.1073/pnas.0902971106.</p> <p>Wang A.Y., Schulze J.M., Skordalakes E., Gin J.W., Berger J.M., Rine J., and Kobor M.S. (2009). ASF1-like structure of the conserved yaf9 yeats domain and role in H2A.Z deposition and acetylation. Proc Natl Acad Sci USA. 106(51): 21573–21578. doi.org/10.1073/pnas.0906539106.</p> <p>Lévesque N., Leung G.P., Fok A.K., Schmidt T.I., and Kobor M.S. (2010). Loss of H3 K79 trimethylation leads to suppression of RTT107-dependent DNA damage sensitivity through the translesion synthesis pathway. J Biol Chem. 285(45):35113–35122. //doi.org/10.1074/jbc.m110.116855.</p> <p><strong>Research Group Members</strong></p> <p>Paola Arguello Pascualli, Graduate Student</p> <p>Parmida Atashzay, Research Assistant/ Technician</p> <p>Hilary Brewis, Graduate Student</p> <p>Meingold Chan, PhD, Postdoctoral Fellow</p> <p>Kristy Dever, MSc, Research Scientist</p> <p>Joe Dong, Graduate Student</p> <p>Karlie Edwards, Graduate Student</p> <p>Hannah-Ruth Engelbrecht, MSc, Graduate Student</p> <p>Tanya Erb, Research Manager</p> <p>Maggie Fu, Graduate Student</p> <p>Marcia Jude, MSc, Bioinformatician</p> <p>Alan Kerr, MRes, Research Facilitator</p> <p>Alyssa Kirlin, MSc, Graduate Student</p> <p>Chaini Konwar, PhD, Bioinformatician</p> <p>Dorothy Lin, Graduate Student</p> <p>Paula Littlejohn, PhD, Postdoctoral Fellow</p> <p>Julie MacIsaac, PhD, Lab Manager and Research Scientist</p> <p>Sarah Merrill, PhD, Postdoctoral Fellow</p> <p>Erick Navarro, Graduate Student</p> <p>Samantha Schaffner, Graduate Student</p> <p>Lea Separovic, Graduate Student</p> <p>Rui Wang, Graduate Student</p> <p>Joanne Whitehead, PhD, Bioinformatician</p> <p>Beryl Zhuang, MSc, Bioinformatician</p> </div> </div> <div class="research field-item full"> <div class="field-shell field-shell-research "> <div class="field" data-count="0"> <div class="textarea"></div> </div> </div> </div> <div class="publications field-item full"> <div class="field-shell field-shell-publications "> <div class="field" data-count="0"> <div class="textarea"></div> </div> </div> </div> </div><!-- .entry-content --> </div><!-- .hentry --> <div id="utility-after-content" class="sidebar utility "> </div><!-- #utility-after-content .utility --> </div><!-- .content .hfeed --> </div> </div><!-- #container --> </div> <div class="row-fluid expand content"> <div id="subsidiary" class="sidebar aside span-12"> <div id="block-3" class="widget widget_block widget-widget_block"><div class="widget-wrap widget-inside"> <figure class="wp-block-table aligncenter"><table><tbody><tr><td><strong>Medical Genetics Graduate Program</strong><br><strong>Phone:</strong>&nbsp;604-822-5312<br><strong>Email:&nbsp;</strong><a href="mailto:medical.genetics@ubc.ca">medical.genetics@ubc.ca</a></td><td>⠀⠀</td><td><strong>MSc Genetic Counselling Program</strong><br><strong>Phone:</strong>&nbsp;604-875-3486<br><strong>Email:&nbsp;</strong><a href="mailto:medgeneducation@cw.bc.ca">medgeneducation@cw.bc.ca</a></td><td>⠀⠀</td><td><strong>Graduate Certificate in<br>Genomic Counselling and Variant</strong> <strong>Interpretation</strong><br><strong>Phone:</strong> 604-875-3486<br><strong>Email: </strong><a href="mailto:genomiccounselling.info@ubc.ca">genomiccounselling.info@ubc.ca</a></td></tr></tbody></table></figure> </div></div> </div><!-- #subsidiary .aside --> </div><!-- .row-fluid --> <!-- CLF Footer --> <footer id="ubc7-footer" class="expand" role="contentinfo"> <div class="row-fluid expand" id="ubc7-unit-footer"> <div class="container"> <div class="span10" id="ubc7-unit-address"> <div id="ubc7-address-unit-name">UBC Department of Medical Genetics</div> <div id="ubc7-address-street"> </div> <div id="ubc7-address-location"> <span id="ubc7-address-city">Vancouver</span>, <span id="ubc7-address-province">BC</span> <span id="ubc7-address-country">Canada</span> <span id="ubc7-address-postal"> </span> </div> </div> </div> </div> <div class="row-fluid expand ubc7-back-to-top"> <div class="container"> <div class="span2"> <a href="#" title="Back to top">Back to top <div class="ubc7-arrow up-arrow grey"></div></a> </div> </div> </div> <div class="row-fluid expand" id="ubc7-global-footer"> <div class="container"> <div class="span5" id="ubc7-signature"><a href="https://www.ubc.ca/" title="The University of British Columbia (UBC)">The University of British Columbia</a></div> <div class="span7" id="ubc7-footer-menu"> </div> </div> </div> <div class="row-fluid expand" id="ubc7-minimal-footer"> <div class="container"> <div class="span12"> <ul> <li><a href="https://cdn.ubc.ca/clf/ref/emergency" title="Emergency Procedures">Emergency Procedures</a> <span class="divider">|</span></li> <li><a href="https://cdn.ubc.ca/clf/ref/terms" title="Terms of Use">Terms of Use</a> <span class="divider">|</span></li> <li><a href="https://cdn.ubc.ca/clf/ref/copyright" title="UBC Copyright">Copyright</a> <span class="divider">|</span></li> <li><a href="https://cdn.ubc.ca/clf/ref/accessibility" title="Accessibility">Accessibility</a></li> </ul> </div> </div> </div> </footer> <!-- End of CLF Footer --> </div><!-- #body-container --> <script type="text/javascript"> jQuery(function () { jQuery('.section-widget-tabbed .nav-tabs a, widget-inside .nav-tabs a').click(function (e) { e.preventDefault(); 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