Tak Wah Mak
University of Toronto
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Primary Section: 43, Immunology and Inflammation Secondary Section: 41, Medical Genetics, Hematology, and Oncology Membership Type:
International Member
(elected 2002)
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Research Interests
My laboratory is engaged in basic research work on the genetics and molecular biology of cancer and the immune system, and the translation of these findings to the clinic. Our early discoveries, including the cloning of human TCR genes, laid the ground work for our understanding of much of T cell biology and provided the basis for the CAR-T treatments now approved for leukemias and lymphomas. My lab was also among the first to create genetically engineered mouse strains to identify factors associated with susceptibility to immune disorders or various cancers. We used these mutant animals to elucidate numerous molecules involved in immune responses (CD4, CD8, CD27, CD45, Lck, etc.), cell death (TNF-R1, Apaf1, cytochrome c, etc.) and tumorigenesis (PTEN, Brca1, Brca2, Chk2, Bcl-10, DJ-1, etc.). My group was the first to reveal that CTLA4 is a negative regulator of T cell activation, paving the way for the development of the immune checkpoint blockade agents now used for cancer immunotherapy. Also in the cancer realm, my team has delineated metabolic vulnerabilities in tumour cells that can be exploited as novel cancer therapies. This strategy has produced two first-in-class drugs aimed at cancer cell metabolism (inhibitors of isocitrate dehydrogenases) that are now FDA-approved for treatment of certain leukemias. In addition, my group has developed three agents that target the aneuploid cancer cells common in advanced solid tumours; these agents are now in clinical trials. Most recently, we have shown that the brain communicates with the immune system via T and B cells producing acetylcholine, a finding that has profound implications for future treatments of cancer and autoimmune or neurodegenerative diseases.
