Jason Moffat

Senior Scientist, Genetics & Genome Biology

Dr. Jason Moffat is an expert in functional genomics with over 20 years’ experience in the field of mammalian cell genomics. He completed his post-doctoral studies at the Whitehead Institute and the Broad Institute of MIT and Harvard where he helped to establish the RNAi Consortium (TRC), which developed the first lentiviral-based short hairpin RNA (shRNA) libraries and methods for genetic screening in human and mouse cells [Moffat et al., Cell, 2006].

Moffat was a key architect of what is an international prototype for an RNAi screening facility at the Whitehead Institute, expertise that he brought with him to the Donnelly Centre at the University of Toronto, where he served as Professor since 2007. Upon joining the Donnelly Centre Moffat established a lentiviral screening platform that has contributed to over 100 research projects and over 50 publications since its inception.

The Moffat lab is committed to pursuing technology development in the field of mammalian functional genomics. In 2015, his lab created one of the first genome-scale CRISPR gRNA libraries for pooled functional screening of human cells, the Toronto Knockout (TKO) CRISPR gRNA library, targeting all human coding genes [Hart et al., Cell, 2015].

He has co-authored over 150 publications which have garnered over 22,000 citations. His research has been covered by various media outlets including The Atlantic, the CBC, Macleans, Motherboard, and The Globe and Mail. Since starting his independent research group in 2007, Moffat has trained 31 graduate students, 37 post-doctoral fellows and 20 visiting and undergraduate students.

Moffat has co-founded three biotechnology companies, he has held a Tier 2 Canada Research Chair in Functional Genomics of Cancer and also held the Anne & Max Tenebaum Chair in Molecular Medicine. 

Research

The goal of Moffat’s research is to understand the function of signaling networks that control cell fitness (i.e., growth, proliferation, survival, and death) by cataloging essential genes and genetic interactions. His main interest is studying how genetic networks are altered in various types of cancer, particularly in response to gene perturbation. To enable this research, his group is focused on technology development aimed at understanding genetic circuits that control cellular responses to changing conditions. More specifically, the Moffat Lab has developed genome-wide gene perturbation methods and data analytics approaches to systematically identify fitness genes in human and mouse cell lines. During these efforts, they built gold standard gene sets for functional genomics that have helped facilitate quality assessment of genome-wide loss-of-function screens in mammalian cells. Moreover, his group conceptualized the “Daisy model of gene essentiality”, which they have used to identify core and context-dependent gene sets for cancer cell line fitness, human embryonic stem cell fitness, and cancer intrinsic evasion to cytotoxic T cells. Systematic genetic screening efforts to catalogue essential genes and genetic interactions promotes gene annotation efforts, reveals functions for uncharacterized genes, unveils drug mechanisms of action, and illuminates genetic principles.

A driving belief of his work is that effective therapeutic strategies can be found through understanding genetic wiring circuits underlying cell state, consistent with a Personalized Medicine approach but more accurately referred to as Network Medicine. This type of research requires interdisciplinary science that includes quantitative experimental biology, machine learning and computational biology, and a deep understanding of model systems and cancer biology.

Experience

• 2018–2022: Professor, Donnelly Centre, Institute for Biomedical Engineering (IBME), University of Toronto
• 2017–2022: Professor, Donnelly Centre, Department of Molecular Genetics, University of Toronto
• 2012–2017: Associate Professor, Donnelly Centre, Department of Molecular Genetics, University of Toronto
• 2007–2012: Assistant Professor, Donnelly Centre & Banting and Best Department of Medical Research, Department of Molecular Genetics, University of Toronto

Education

• 2005–2007: Visiting Fellow, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
• 2004–2007: Postdoctoral Fellow, Whitehead Institute of Biomedical Research, Cambridge, Massachusetts, USA
• 2003–2004: Postdoctoral Fellow, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
• 1996–2002: PhD, Molecular Genetics, University of Toronto, Toronto, ON, Canada
• 1991–1996: B.Sc. (Hon) (1st class) / Co-op Biochemistry, Queen's University, Kingston, ON, Canada

Achievements

• 2022: Anne & Max Tanenbaum Chair in Molecular Medicine (5 months)
• 2012–2022: Canada Research Chair (CRC) in Functional Genomics of Cancer, Tier 2
• 2007–2019: Canadian Institute for Advanced Research (CIFAR), Senior Fellow
• 2009–2012: Canadian Institutes for Health Research (CIHR) New Investigator Award

1. Hart T, Chandrashekhar M, Aregger M, Steinhart Z, Brown KR, MacLeod G, Mis M, Zimmermann M, Fradet-Turcotte A, Sun S, Mero P, Dirks P, Sidhu S, Roth FP, Rissland OS, Durocher D, Angers S, Moffat J. High-Resolution CRISPR Screens Reveal Fitness Genes and Genotype-Specific Cancer Liabilities. Cell. 2015 Dec 3;163(6):1515-26. 
2. Gonatopoulos-Pournatzis T, Aregger M, Brown KR, Farhangmehr S, Braunschweig U, Ward HN, Ha KCH, Weiss A, Billman M, Durbic T, Myers CL, Blencowe BJ, Moffat J. Genetic interaction mapping and exon-resolution functional genomics with a hybrid Cas9-Cas12a platform. Nat Biotech. 2020 May;38(5):638-648. 
3. Aregger M, Lawson KA, Billmann M, Costanzo M, Tong AHY, Chan K, Rahman M, Brown KR, Ross C, Usaj M, Nedyalkova L, Sizova O, Habsid A, Pawling J, Lin ZY, Abdouni H, Wong CJ, Weiss A, Mero P, Dennis JW, Gingras AC, Myers CL, Andrews BJ, Boone C, Moffat J. Systematic mapping of genetic interactions for de novo fatty acid synthesis identifies C12orf49 as a regulator of lipid metabolism. Nat Metab. 2020 Jun; 2(6):499-513. 
4. Lawson KA, Sousa CM, Zhang X, Kim E, Akthar R, Caumanns JJ, Yao Y, Mikolajewicz N, Abou Zid A, Fan ZP, Hui S, Krall JA, Simons DM, Slater CJ, De Jesus V, Tang L, Singh R, Goldford JE, Martin S, Huang Q, Francis EA, Habsid A, Climie R, Tieu D, Wei J, Li R, Tong AHY, Aregger M, Chan KS, Han H, Wang X, Mero P, Brumell JH, Finelli A, Ailles L, Bader G, Smolen GA, Kingsbury GA, Hart T, Kung C, Moffat J. Functional genomic landscape of cancer-intrinsic evasion of killing by T cells. Nature, 2020 Oct; 586(7827):120-126. 
5. Marcotte R, Brown KR, Suarez F, Sayad A, Karamboulas K, Krzyzanowski PM, Sircoulomb F, Medrano M, Fedyshyn Y, Koh JLY, van Dyk D, Fedyshyn B, Luhova M, Brito GC, Vizeacoumar FJ, Vizeacoumar FS, Datti A, Kasimer D, Buzina A, Mero P, Misquitta C, Normand J, Haider M, Ketela T, Wrana JL, Rottapel R, Neel BG, Moffat J. Essential gene profiles in breast, pancreatic, and ovarian cancer cells. Cancer Discov. 2012 Feb;2(2):172-189. 

See a full list of Dr. Moffat's publications on NCBI, PubMed or Google Scholar.