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Martin Hirst

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Martin Hirst

Associate Professor

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Associated Departments

Department of Microbiology & Immunology

Research Area

Dr. Hirst’s research aims to further our understanding of the role of epigenetic dysfunction in cancer initiation and progression and to translate this knowledge into improved health outcomes for Canadians.

International efforts to characterize genetic lesions in cancer genomes have revealed recurrent mutations in epigenetic modifiers and in some cases these can represent the sole driver. Understanding the functional implications of these mutations, their contribution to abnormal cellular differentiation and how emerging epigenetic therapeutics may counteract their effects represent the next critical steps towards translating this knowledge. In this context, Dr. Hirst is studying cancers that harbor highly recurrent gain and loss of function mutations to epigenetic modifiers, such as acute myeloid leukemia, synovial sarcoma, malignant rhabdoid tumor.  His research involves the development and application of molecular and computational tools to measure epigenetic features and drive new insights into normal and pathogenic epigenetic regulatory control.

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Selected Publications:

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Xiaoyang Lan, David J. Jörg, Florence M. G. Cavalli, Laura M. Richards, Long V. Nguyen, Robert J. Vanner, Paul Guilhamon, Lilian Lee, Michelle M. Kushida, Davide Pellacani, Nicole I. Park, Fiona J. Coutinho, Heather Whetstone, Hayden J. Selvadurai, Clare Che, Betty Luu, Annaick Carles, Michelle Moksa, Naghmeh Rastegar, Renee Head, Sonam Dolma, Panagiotis Prinos, Michael D. Cusimano, Sunit Das, Mark Bernstein, Cheryl H. Arrowsmith, Andrew J. Mungall, Richard A. Moore, Yussanne Ma, Marco Gallo, Mathieu Lupien, Trevor J. Pugh, Michael D. Taylor, Martin Hirst, Connie J. Eaves, Benjamin D. Simons & Peter B. Dirks. Fate mapping of human glioblastoma reveals an invariant stem cell hierarchy. Nature (2017)

M Mingay, A Chaturvedi, M Bilenky, Q Cao, L Jackson, T Hui, M Moksa, A Heravi-Moussavi, R K Humphries, M Heuser and M Hirst. Vitamin C-induced epigenomic remodelling in IDH1 mutant acute myeloid leukaemia. Leukemia, June 30., 2017.

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; 

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.