Position/Role: Associate Professor
Affiliation: Department of Microbiology & Immunology
Email Address: hirst[at]chibi.ubc.ca
Phone: 604 822-6373
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.
Hendrik G. Stunnenberg, The International Human Epigenome Consortium, and Martin Hirst – The International Human Epigenome Consortium: A Blueprint for Scientific Collaboration and Discovery -Cell 167, November 17, 2016
Alireza Lorzadeh, Misha Bilenky, Colin Hammond, David J.H.F. Knapp, Luolan Li, Paul H. Miller, Annaick Carles, Alireza Heravi-Moussavi, Sitanshu Gakkhar, Michelle Moksa, Connie J. Eaves and Martin Hirst. Nucleosome Density ChIP-Seq Identifies Distinct Chromatin Modification Signatures Associated with MNase Accessibility. Cell Reports 17, 2112–2124, November 15, 2016
Davide Pellacani, Misha Bilenky, Nagarajan Kannan, Alireza Heravi-Moussavi, David J.H.F. Knapp, Sitanshu Gakkhar, Michelle Moksa, Annaick Carles, Richard Moore, Andrew J. Mungall, Marco A. Marra, Steven J.M. Jones, Samuel Aparicio, Martin Hirst and Connie J. Eaves. Analysis of Normal Human Mammary Epigenomes Reveals Cell-Specific Active Enhancer States and Associated Transcription Factor Networks. Cell Reports 17, 2060–2074, November 15, 2016
Chun HJ, Lim EL, Heravi-Moussavi A, Saberi S, Mungall KL, Bilenky M, Carles A, Tse K, Shlafman I, Zhu K, Qian JQ, Palmquist DL, He A, Long W, Goya R, Ng M, LeBlanc VG, Pleasance E, Thiessen N, Wong T, Chuah E, Zhao YJ, Schein JE, Gerhard DS, Taylor MD, Mungall AJ, Moore RA, Ma Y, Jones SJ, Perlman EJ, Hirst M, Marra MA. Genome-Wide Profiles of Extra-cranial Malignant Rhabdoid Tumors Reveal Heterogeneity and Dysregulated Developmental Pathways. Cancer Cell. 2016 Mar 14
Nguyen LV, Pellacani D, Lefort S, Kannan N, Osako T, Makarem M, Cox CL, Kennedy W, Beer P, Carles A, Moksa M, Bilenky M, Balani S, Babovic S, Sun I, Rosin M, Aparicio S, Hirst M, Eaves CJ. Barcoding reveals complex clonal dynamics of de novo transformed human mammary cells. Nature. 2015 Dec 10
Pon JR, Wong J, Saberi S, Alder O, Moksa M, Grace Cheng SW, Morin GB, Hoodless PA, Hirst M, Marra MA. MEF2B mutations in non-Hodgkin lymphoma dysregulate cell migration by decreasing MEF2B target gene activation. Nat Commun. 2015 Aug 6
Gascard P, Bilenky M, Sigaroudinia M, Zhao J, Li L, Carles A, Delaney A, Tam A, Kamoh B, Cho S, Griffith M, Chu A, Robertson G, Cheung D, Li I, Heravi-Moussavi A, Moksa M, Mingay M, Hussainkhel A, Davis B, Nagarajan RP, Hong C, Echipare L, O’Geen H, Hangauer MJ, Cheng JB, Neel D, Hu D, McManus MT, Moore R, Mungall A, Ma Y, Plettner P, Ziv E, Wang T, Farnham PJ, Jones SJ, Marra MA, Tlsty TD, Costello JF, Hirst M. Epigenetic and transcriptional determinants of the human breast. Nat Commun. 2015 Feb 18
Roadmap Epigenomics Consortium, Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A, … Hirst M, Meissner A, Milosavljevic A, Ren B, Stamatoyannopoulos JA, Wang T, Kellis M. Integrative analysis of 111 reference human epigenomes. Nature. 2015 Feb 19
Nguyen LV, Cox CL, Eirew P, Knapp DJ, Pellacani D, Kannan N, Carles A, Moksa M, Balani S, Shah S, Hirst M, Aparicio S, Eaves CJ. DNA barcoding reveals diverse growth kinetics of human breast tumour subclones in serially passaged xenografts. Nat Commun. 2014 Dec 23
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.
Stevens, M., Cheng, J. B., Li, D., Xie, M., Hong, C., Maire, C. L., Ligon, K.L., Hirst, M., Marro, M.A., Costello, J.F., & Wang, T. Estimating absolute methylation levels at single-CpG resolution from methylation enrichment and restriction enzyme sequencing methods. Genome research 2013 June 13; 23:1541-1553.
Xie, M., Hong, C., Zhang, B., Lowdon, R. F., Xing, X., Li, D., … Hirst, M., … & Wang, T. DNA hypomethylation within specific transposable element families associates with tissue-specific enhancer landscape. Nature genetics 2013 May 26; 45:836-841.
Dvinge, H., Git, A., Gräf, S., Salmon-Divon, M., Curtis, C., Sottoriva, A., … Hirst, M., … & Caldas, C. The shaping and functional consequences of the microRNA landscape in breast cancer. Nature 2013 May 5; 497: 378-382.
Pugh, T. J., Morozova, O., Attiyeh, E. F., Asgharzadeh, S., Wei, J. S., Auclair, D., … Hirst, M., … & Gerhard, D. S. The genetic landscape of high-risk neuroblastoma. Nature genetics 2013 January 20; 45:279-284.
Falconer, E., Hills, M., Naumann, U., Poon, S. S., Chavez, E. A., Sanders, A. D., Zhao, Y., Hirst, M., & Lansdorp, P. M. DNA template strand sequencing of single-cells maps genomic rearrangements at high resolution. Nature methods 2012 October 7; 9:1107-1112.
Muzny, D. M., Bainbridge, M. N., Chang, K., Dinh, H. H., Drummond, J. A., Fowler, G., … Hirst, M., … & Chuah, E. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012 July 18; 487: 330-337.