• Kobor, Michael Steffen

    Titles

    Investigator, BC Children's Hospital
    Senior Scientist, Centre for Molecular Medicine and Therapeutics at CFRI
    Professor, Department of Medical Genetics, The University of British Columbia
    Tier 1 Canada Research Chair in Social Epigenetics

    Degrees / Designations
    Diploma in Biology, PhD
    Primary Area of Research
    Healthy Starts
    Secondary Area(s) of Research
    Phone
    604-875-3803
    Fax
    604-875-3840
    Lab Phone
    604-875-3833
    Assistant
    Tanya Erb
    Assistant Phone
    604-875-2345 ext. 5901
    Mailing Address
    BC Children's Hospital
    Room 2008, 950 West 28th Avenue
    Vancouver, BC V5Z 4H4 
    Affiliate Websites
    Research Areas
    • Developmental origins of disease
    • Biological embedding of early experiences
    • Epigenetic epidemiology
    • Gene regulation
    • Gene-Environment Interactions
    • Functional genomics
    Summary
    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 histone, and nucleosome positioning. Additionally, genetic variation may interact with specific environments, imparting sensitivity or resilience, to ultimately alter epigenetics patterns and phenotypic outcomes.
    Current Projects
    In one facet of our research program, we study human population epigenetics aimed at deciphering the mechanisms by which environmental exposures and early-life experiences can "get under the skin" to regulate gene activity and contribute to health and disease across the life course. This research aligns with the Developmental Origins of Health and Disease (DOHaD) hypothesis, which postulates that the developmental period and early life are particularly sensitive periods where social or environmental insults can influence health long after the insult itself. Our findings support the model that early-life social and environmental factors, including stress and socioeconomic status, leave a biological footprint. We measure this biological embedding of early life exposures through epigenetic patterns and accompanying gene expression changes, many of which are maintained until adulthood and may influence future health. We have extensive interdisciplinary collaborations across Canada and around the world and are affiliated with multiple NCEs (including AllerGen and NeuroDevNet).

    Rather than acting as an inert scaffold for DNA, dynamic and flexible chromatin structures and modifications have profound effects on almost all aspects of chromosome behaviour and genome function. Thus, the second objective of our research utilizes Saccharomyces cerevisiae as a model organism to tease apart the mechanisms responsible for the creation, regulation, and maintenance of the chromatin signature. These queries include how distinct chromosomal neighbourhoods are established, how they function and interact with enzymes involved in DNA metabolism, what functional differences exist between histone variants and canonical histones, and how chromatin-remodeling complexes are regulated. Currently, we focus on three distinct areas of chromatin biology: functional genomic characterization of chromatin-modifying complexes; DNA damage repair in the context of the chromatin template; and crosstalk between the RNAPII machinery and chromatin. 

    Together, the research in our lab bridges the molecular mechanisms of epigenetic regulation with the social and environmental determinants of human health to develop a comprehensive understanding of early life.
    Selected Publications

    Chen L., Pan H. Tuan T.A., Teh A.L., MacIsaac J.L., Mah S.M., McEwen L.M., Li Y., Chen H., Broekman B.F., Buschdorf J.P., Chong Y.S., Kwek K., Saw S.M., Gluckman P.D., Fortier M.V., Rifkin-Graboi A., Kobor M.S., Qiu A., Meaney M.J., and Holbrook J.D; GUSTO Study Group. (2015) Brain-derived Neurotrophic Factor (BDNF) Val66Met Polymorphism Influences the Association of the Methylome with Maternal Anxiety and Neonatal Brain Volumes. Dev Psychopathol 271:137-50.

    Boyce W.T., and Kobor M.S. (2015) Development and the Epigenome: The ‘Synapse’ of Gene - Environment Interplay. Dev Sci 18:1-23.

    Lu PY, Kobor MS. (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):133-45.

    Teh A.L., Pan H., Chen L., Ong M.L., Dogra S., Wong J., MacIsaac J.L., Mah S.M., McEwen L.M., Saw S.M., Godfrey K.M., Chong Y.S., Kwek K., Kwoh C.K., Soh S.E., Barton S., Karnani N., Cheong C.Y., Buschdorf J.P., Stunkel W., Kobor M.S., Meaney M.J., Gluckman P.D., and Holbrook J.D. (2014) The Effect of Genotype and in utero Environment on Inter-individual Variation in Neonate DNA Methylomes. Genome Res 24:1064-74.

    Aristizabal MJ, Negri GL, Benschop JJ, Holstege FC, Krogan NJ, Kobor MS. (2013) High-throughput genetic and gene expression analysis of the RNAPII-CTD reveals unexpected connections to SRB10/CDK8. PLoS Genet 9(8):e1003758.

    Lam L.L., Emberly E., Fraser H.B., Neumann S.M., Chen E., Miller G.E. and Kobor M.S. (2012) Factors Underlying Variable DNA Methylation in a Human Community Cohort. Proc Natl Acad Sci USA 109 Suppl 2:17253-60.

    Fraser H.B., Lam L.L., Neumann S.M., and Kobor M.S. (2012) Population-specificity of Human DNA Methylation. Genome Biol 13:R8.

    Wang AY, Aristizabal MJ, Ryan C, Krogan NJ, Kobor MS. (2011). Key functional regions in the histone variant H2A.Z C-terminal docking domain. Mol Cell Biol 31(18):3871-84. 

    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 84:58-75.

    Yuen R.K., Neumann S.M., Fok A.F., Peñaherrera M.S., McFadden D.E., Robinson W.P., and Kobor M.S. (2011) Extensive Epigenetic Reprogramming in Human Somatic Tissues between Fetus and Adult.  Epigenetics Chromatin 4:7.

    Lévesque N, Leung GP, Fok AK, Schmidt TI, Kobor MS. (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):35113-22.  

    Chen E., Miller G.E., Kobor M.S., and Cole S.W. (2010) Maternal Warmth Buffers the Effects of Low Early-Life Socioeconomic Status on Pro-Inflammatory Signalling in Adulthood. Mol Psychiatry 16:729-37.

    Wang AY, Schulze JM, Skordalakes E, Gin JW, Berger JM, Rine J, Kobor MS. (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):21573-8.

    Schulze JM, Jackson J, Nakanishi S, Gardner JM, Hentrich T, Haug J, Johnston M, Jaspersen SL, Kobor MS, Shilatifard A. (2009) Linking cell cycle to histone modifications: SBF and H2B monoubiquitination machinery and cell-cycle regulation of H3K79 dimethylation. Mol Cell 35(5):626-41.

    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 106:14716-21.

    Grants
    Honours & Awards

    Canada Research Chair Tier 1 in Social Epigenetics, 2014-present
    Senior Fellow, Canadian Institute for Advanced Research, Child & Brain Development program, 2013-present
    Award of Excellence, Biomedical Research, CFRI Member Recognition Awards, 2013
    Connaught Global Challenge Distinguished Visiting Professor at the Fraser Mustard Institute for Human Development, University of Toronto, 2013
    Early Career Scholar, UBC Peter Wall Institute, 2012-2013
    Distinguished Achievement Award for Excellence in Basic Science Research, UBC Faculty of Medicine, 2012
    Mowafaghian Foundation Young Scholar, 2010-2014
    Fellow, Canadian Institute for Advanced Research, Experience-based Brain and Biological Development program 2006-present
    Michael Smith Foundation for Health Research Scholar, 2005 
    Postdoctoral Fellowship Human Frontier Science Program, 2000-2003 

    Research Group Members
    Maria Aristizabal, Postdoctoral Fellow 
    Sachini Ariyaratne, MSc Student
    Josh Brown, PhD Candidate 
    Nicole Couto, PhD Candidate
    Rachel Edgar, Research Assistant 
    Tanya Erb, Administrative Manager
    Sarah Goodman, PhD Candidate
    Sumaiya Islam, PhD Candidate
    Meaghan Jones, Postdoctoral Fellow
    Alyssa Kirlin, PhD Candidate
    Phoebe Lu, Postdoctoral Fellow
    Alexandre Lussier, PhD Student
    Julie MacIsaac, Research Associate / Lab Manager
    Lisa McEwen, PhD Student
    Alexander Morin, Research Assistant
    Mina Park, PhD Student
    Olivia Wong, MSc Student