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/hirst.
Rebollo R, Karimi MM, Bilenky M, Gagnier L, Miceli-Royer K, Zhang Y, Goyal P, Keane TM, Jones S, Hirst M, Lorincz MC & Mager DL. Variation in retrotransposon-induced heterochromatin spreading in the mouse revealed by insertional polymorphisms. PLoS Genetics. 2011 Sep;7(9):e1002301. Epub 2011 Sep 29.
Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, McDonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJ, Connors JM, Hirst M, Gascoyne RD, Marra MA. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature 2011 Jul 27; 476(7360): 298- 303.
Schrader KA, Heravi-Moussavi A, Waters PJ, Senz J, Whelan J, Ha G, Eydoux P, Nielsen T, Gallagher B, Oloumi A, Boyd N, Fernandez BA, Young TL, Jones SJ, Hirst M, Shah SP, Marra MA, Green J, Huntsman DG. Using next-generation sequencing for the diagnosis of rare disorders: a family with retinitis pigmentosa and skeletal abnormalities. J Pathol. 2011 Sep;225(1):12-8
O'Connor MD, Wederell E, Robertson G, Delaney A, Morozova O, Poon SS, Yap D, Fee J, Zhao Y, McDonald H, Zeng T, Hirst M, Marra MA, Aparicio SA, Eaves CJ. Retinoblastoma-binding proteins 4 and 9 are important for human pluripotent stem cell maintenance. Exp Hematol. 2011 Aug;39(8):866-879.e1.
McPherson A, Hormozdiari F, Zayed A, Giuliany R, Ha G, Sun MG, Griffith M, Heravi Moussavi A, Senz J, Melnyk N, Pacheco M, Marra MA, Hirst M, Nielsen TO, Sahinalp SC, Huntsman D, Shah SP. deFuse: an algorithm for gene fusion discovery in tumor RNA-Seq data. PLoS Comput Biol. 2011 May;7(5):e1001138.
Martin Hirst's Complete Publication List including selected links to full text articles.