Epigenetics, the study of how covalent modifications to DNA and histones impact gene expression, is an emerging field with relevance to human disease. Normal cell development is accompanied by marked changes in the epigenome and specific epigenetic signatures have been identified in pluripotent, somatic and cancer cell types. Epidemiological and model organism studies have demonstrated that epigenetic modification can be induced via diverse environmental stimuli including stress, nutrient levels and toxin exposure. Epigenetic modification, which can be both transient and heritable in nature, thus provides a framework in which to investigate how environment and lifestyle choices impact disease susceptibility and progression. Furthermore, epigenetic modifications are central to chromatin dynamics and, as such, play key roles in many biological processes involving chromatin, such as DNA replication and repair, transcription and development. Our current understanding of the full repertoire of epigenetic modifications and the processes that they regulate is incomplete and we have only recently developed tools which allow for the study of normal human epigenomic polymorphism and the role that epigenetics plays in the initiation and progression of disease.
The overall objectives of our lab are directed at understanding the role of epigenetics in cancer and to investigate the therapeutic potential of interventions directed at epigenetic processes. We approach this from an epigenomic perspective by combining innovative molecular biology and computational techniques with genome wide detection platforms. More information about the Hirst research group is available at http://www.chibi.ubc.ca/faculty/martin-hirst/
Our lab publishes our epigenomic data at the Canadian Epigenetics, Environment and Health Research Consortium (CEEHRC).
- Mack, S. C., Witt, H., Piro, R. M., Gu, L., Zuyderduyn, S., Stütz, A. M., … Hirst, M., … & Pereira, S. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature 2014 February 26; 506:445-450.
- Nguyen, L. V., Makarem, M., Carles, A., Moksa, M., Kannan, N., Pandoh, P., … & Hirst, M. Clonal analysis via barcoding reveals diverse growth and differentiation of transplanted mouse and human mammary stem cells. Cell stem cell 2014 February 6; 14:253-263.
- Johnson, B. E., Mazor, T., Hong, C., Barnes, M., Aihara, K., McLean, C. Y., … Hirst, M., … & Costello, J. F. Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Science 2014 January 10; 343:189-193.
- Blaschke, K., Ebata, K.T., Karimi, M.M., Zepeda-Martinez, J.A., Goyal, P., Mahapatra, S., Tam, A., Laird, D.J., Hirst, M., Rao, A., Lorincz, M.C., & Ramalho-Santos, M. Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. Nature 2013 June 30; 500:222-226.
- Zhang, B., Zhou, Y., Lin, N., Lowdon, R. F., Hong, C., Nagarajan, R. P., … Hirst, M., …& Wang, T. Functional DNA methylation differences between tissues, cell types, and across individuals discovered using the M&M algorithm. Genome research 2013 June 13; 23:1522-1540.
Martin Hirst's Complete Publication List including selected links to full text articles.