Dr. Michael Steffen Kobor, PhD
Edwin S.H. Leong UBC Chair in Healthy Aging – a UBC President’s Excellence Chair
Tier 1 Canada Research Chair in Social Epigenetics
Professor, Department of Medical Genetics, University of British Columbia
Investigator, BCCHR
Senior Scientist, Centre for Molecular Medicine and Therapeutics at BC Children’s Hospital Research Institute (BCCHR)
Email: michael.kobor@ubc.ca
Phone: 604-875-3803
Site: https://bcchr.ca/kobor-lab
Assistant: Tanya Erb
Assistant Phone: 604-875-2345 ext. 5901
Mailing Address: Room A5-165, 950 West 28th Avenue, Vancouver BC V5Z 4H4
Overview
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.
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 molecular mechanisms of epigenetic regulation in response to the environment. 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.
Project Overview
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.
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.
Selected Publications
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.
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..
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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.
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.
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.
Research Group Members
Paola Arguello Pascualli, Graduate Student
Parmida Atashzay, Research Assistant/ Technician
Hilary Brewis, Graduate Student
Meingold Chan, PhD, Postdoctoral Fellow
Kristy Dever, MSc, Research Scientist
Joe Dong, Graduate Student
Karlie Edwards, Graduate Student
Hannah-Ruth Engelbrecht, MSc, Graduate Student
Tanya Erb, Research Manager
Maggie Fu, Graduate Student
Marcia Jude, MSc, Bioinformatician
Alan Kerr, MRes, Research Facilitator
Alyssa Kirlin, MSc, Graduate Student
Chaini Konwar, PhD, Bioinformatician
Dorothy Lin, Graduate Student
Paula Littlejohn, PhD, Postdoctoral Fellow
Julie MacIsaac, PhD, Lab Manager and Research Scientist
Sarah Merrill, PhD, Postdoctoral Fellow
Erick Navarro, Graduate Student
Samantha Schaffner, Graduate Student
Lea Separovic, Graduate Student
Rui Wang, Graduate Student
Joanne Whitehead, PhD, Bioinformatician
Beryl Zhuang, MSc, Bioinformatician