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Dr. Michael Witcher
Senior Investigator, Lady Davis Institute
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).
Recent Publications
Cepeda-Cañedo E, Totten S, Ahn R, Savage P, MacNeil D, Autexier C, Deblois G, Park M, Witcher M* and Ursini-Siegel* (co-corresponding) The p66ShcA Redox Protein Potentiates the Cytotoxic Response of Triple Negative Breast Cancers to PARP Inhibitors. J. Clinical Investigation Insight (JCI Open Access, In press).

Shorstova T, Maud Marques M, Su J, Johnston J, Kleinman CL, Hamel N, Huang S, Alaoui-Jamali MA, Foulkes WD and Witcher M* Susceptibility of SMARCA4 deficient cancers to bromodomain inhibitors Cancer Research, 2019 May 15;79(10):2761-2774.

Marques M, Jangal M, Wang LC, Kazanets A, da Silva SD, Zhao T, Lovato A, Yu H, Jie S, Del Rincon S, Mackey J, Damaraju S, Alaoui-Jamali M and Witcher M*  Oncogenic activity of Poly (ADP-ribose) glycohydrolase Oncogene, Mar;38(12):2177-2191.

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). 2017 May 24;3(5):e1601898.
Dr. Witcher's key research projects include:

Exploring how key epigenetic regulatory proteins, such as CTCF, play multiple roles in prohibiting tumor initiation through activation of tumor suppressors, coordinating DNA repair, and maintaining genome integrity.

Investigating the impact of post-translation modification by PARP-1 and PARG on the expression of tumor suppressor genes.

Pharmacologic manipulation of epigenetic processes to inhibit cancer cell growth.
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