Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Mak, Tak Wah
Location University of Toronto
Primary Field Immunology and Inflammation
Secondary Field Medical Genetics, Hematology and Oncology
 Election Citation
From Canada, Mak discovered the human T cell receptor genes and explained how the different types of T cells are created. He also made the pioneering discovery that a single gene from the Friend leukemia virus could induce acute myelogenous leukemia. More recently, he has isolated and analyzed the effect of key genes that regulate the immune system and suppress tumors, paving the way for future therapies.
 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.

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