Associate Professor, Department of Oncology, McGill University
Dr. Witcher's Publications Indexed on PubMed
Dr. Michael Witcher is an associate professor of Medicine, at McGill University, affiliated with the Department of Oncology, a Senior Investigator at the Lady Davis Institute for Medical Research and a member of the Jewish General Hospital/Segal Cancer Center. He received a BSc and MSc from Memorial University of Newfoundland, a PhD from McGill, and carried out postdoctoral training at the Salk Institute in California.
Major Research Activities
While cancer is an extraordinarily heterogeneous disease, all human malignancies involve genome wide changes in transcription. Dr. Witcher’s research career has focused on elucidating the mechanisms whereby transcription becomes deregulated in cancer. His lab aims to define the mechanisms whereby tumor suppressors become silenced and oncogenes become aberrantly activated and to utilize this information to design new therapeutic avenues to kill malignant growth.
CTCF is commonly referred to as “The Master Weaver of the Genome” and plays a critical role in repressing oncogenic transcriptional activity across the genome. As such, CTCF is commonly a target for dysfunction in cancer through multiple mechanisms including deletion, mutation and loss of the post-translational modification poly (ADP-ribosylation). Using integrated approaches including Mass-Spec, RNA-seq, ChIP-seq and animal models of cancer, the group is defining the impact of dysfunctional CTCF on diverse processes including gene regulation, epigenetic programming and DNA damage repair (eg. PNAS 2015, Science Advances 2017).
The Witcher lab is also engaged in several projects where they have identified new biomarkers predicting the efficacy of drugs targeting epigenetic processes (manuscript in preparation). They are also actively engaged in projects aimed at optimizing the clinical use of PARP-inhibitors (BMC Medicine 2015) and finding novel means to drug the poly (ADP-ribose) pathway (manuscript in preparation).
Peña-Hernández R, Marques M, Hilmi K, Zhao T, Saad A, Alaoui-Jamali MA, Del Rincon SV, Ashworth T, Roy AL, Emerson BM, Witcher M. Genome-wide targeting of the epigenetic regulatory protein CTCF to gene promoters by the transcription factor TFII-I. Proc Natl Acad Sci U S A. 2015 Feb 17;112(7):E677-86. doi: 10.1073/pnas.1416674112.
Hilmi K, Jangal M, Marques M, Zhao T, Saad S, Zhang C, Luo VM, Syme A, Rejon C, Yu Z, Krum A, Fabian MR, Richard S, Alaoui-Jamali M, Orthwein A, McCaffrey L and Witcher M. CTCF facilitates DNA double-strand break repair by enhancing homologous recombination repair. Science Advances (AAAS, Science). Accepted, in press
Marques M, Beauchamp MC, Laskov I, Qiang S, Gotlieb WH and Witcher M. Chemotherapy depletes PARP1 protein in ovarian cancer tumors: Implications for future clinical trials involving PARP inhibitors. BMC Medicine. 2015 Sep 9;13(1):217.