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Regulation of gene expression via chromatin associated factors and alterations of the cellular epigenome are fundamental to most biological processes, and many disease mechanisms. We are taking a protein family approach to understand how chromatin regulatory proteins recognize specific histone tail sequences and their posttranslational modifications. Proteins such as histone methyltransferases, demethylases, acetyltransferases and bromodomains and chromodomains mediate nuclear signaling networks that regulate epigenetic cellular states and gene expression programs. Systematic structural and biochemical analyses of these protein families are revealing key features of selectivity and regulation among these factors, enabling structure-based development of potent, selective, cell-active small molecule inhibitors of individual epigenetic regulatory proteins. Such compounds – Chemical Probes – are extremely valuable for understanding epigenetic signaling mechanisms in cells. Chemical probes are highly complementary to genetic methods and more closely mimic strategies for therapeutic translation. We are providing our epigenetic chemical probes as an open access resource to the biomedical research community to facilitate understanding of epigenetic mechanisms and to more rapidly identify and validate therapeutic targets for cancer and other diseases. I will present our work on Chemical Probes for protein methyltransferases and their characterization in human disease models.
Chief Scientist, Princess Margaret Cancer Centre, The Structural Genomics Consortium
Professor, Department of Medical Biophysics, University of Toronto
12:00 pm at Van Andel Institute
Conference Room 3104/3105
For questions, please contact Kim Cousineau at 616.234.5684.