“Epigenetic and Genetic Collusion in Transformation”
Thursday, April 9, 2015. 6:00pm
Head of Epigenomics, Michael Smith Genome Sciences Centre, BC Cancer Agency
Assistant Professor, Dept. of Microbiology and Immunology, Centre for High-Throughput Biology, University of British Columbia
URL: Martin Hirst
Dr. Hirst’s research is directed at understanding the role of epigenetics in normal development and cancer and investigating the therapeutic potential of interventions directed at epigenetic processes. Dr. Hirst is the co-chair of the scientific steering committee of the International Human Epigenomics Consortium (IHEC) where he also chairs the IHEC assay standards group. As part of the NIH Reference Human Epigenome and Canadian Epigenetics, Environment and Health Research Consortiums Dr. Hirst has generated and analyzed comprehensive epigenomic profiles from a wide range of normal adult, fetal, embryonic and extraembryonic tissues and purified cell types. He has authored more than 100 peer-reviewed papers, primarily in the area of genomics since 1998.
Mammalian genomes carry non-uniform chemical marks covalently attached to DNA bases and their packaging proteins. These chemical marks, which collectively define the epigenome, interact with cellular transcriptional machinery to establish activity states that reinforce gene activation or silencing. In contrast to the genome, which remains largely the same throughout an individual’s life, the epigenome changes during development and aging, in response to various external stimuli and as diseases emerge. Epigenetic changes (epimutations) are an alternative mechanism to genetic mutation by which oncogenes and tumour suppressor genes may be deregulated within a cancer cell. Such changes are prevalent in many cancer types, and their appearance may precede genetic changes in pre-malignant cells and promote the accumulation of additional damaging genetic and epigenetic lesions. Epimutations are potentially reversible and thus provide a therapeutic opportunity not readily available in the context of somatic genetic lesions.
Recent technological advancements have enabled the reproducible assessment of epigenomic marks across the entire genome of human cells and large-scale international efforts are now underway to generate high-resolution reference epigenome maps to accelerate the scientific exploitation of human epigenomic information. The epigenome maps thus generated integrate detailed DNA methylation, histone modification, nucleosome occupancy and coding and non-coding RNA expression in different normal and disease cell types, with the goal of providing new insights into many diseases, including cancer and the discovery of new means to control them.
In this lecture I will provide an overview of our work within the NIH Reference Epigenome Program (nature.com/epigenomeroadmap) and describe how this work supports the broader goals of the International Human Epigenome Consortium (http://ihec-epigenomes.net/). Finally, I will present our recent work utilizing epigenomic mapping techniques to understand the interplay between genetic and epigenetic lesions in cancer.
Trainees are invited to meet with the VanBUG speaker for open discussion of both science and career paths. This takes place 4:30-5:30pm in either the Boardroom or Lunchroom on the ground floor of the BCCRC
Niels Hanson (PhD Candidate, Dr. Steve Hallam’ Lab, UBC)
“MetaPathways: A Modular Pipeline for the Analysis of Environmental Sequence Information”