Biochemistry Experts

Chan, Steven

University of Toronto


Dr. Chan completed his undergraduate training (Immunology specialist program) at University of Toronto in 2000. He received his medical and research training at Stanford University in California where he earned his MD (2008) and PhD (2006) degree in Immunology. He subsequently completed his internal medicine residency (2010) and adult hematology fellowship (2014) at Stanford Hospital and Clinics. He conducted his postdoctoral research under the supervision of Dr. Ravindra Majeti at the Stanford Cancer Institute where he studied the isocitrate dehydrogenase mutation in acute myeloid leukemia and its effects on mitochondrial function. He joined Princess Margaret Cancer Centre as a Clinician Scientist in 2015.

Research Interest

Dr. Steven Chan’s research focus has been to develop novel approaches to target mutations that have been identified through whole genome sequencing efforts in the past 10 years. Although our understanding of the underlying mutations that drive cancer has tremendously improved, the majority of the mutations are unfortunately not easily “druggable” in part because many of them result in a loss-of-function phenotype. If the goal of personalized medicine is to be realized, new therapeutic strategies that specifically target these mutations are required in the armament of drugs. Dr. Chan views this as one of the main challenges facing translational cancer research today. Chan SM, Thomas D, Cores-Zimmerman MR, Xavy S, Rastogi S, Hong WJ, Zhao F, Medeiros BC, Tyvoll DA, Majeti R. 2015. Isocitrate Dehydrogenase 1 and 2 Mutations Induce BCL-2 Dependence in Acute Myeloid Leukemia. Nature Medicine. 21(2):178-84. In the above manuscript, Dr. Chan applied the synthetic lethality strategy to target the isocitrate dehydrogenase (IDH) mutation in AML. IDH mutations are clinically relevant because approximately 15% of AML patients have mutations in either IDH1 or IDH2. Using a functional genomics approach, he identified and validated the BCL-2 gene as a synthetic lethal target against IDH mutations. He further showed that pharmacologic inhibition of BCL-2 with ABT-199 (also known as venetoclax), an orally bioavailable and highly specific BCL-2 inhibitor, preferentially killed AML cells harboring IDH mutations. Furthermore, using xenotransplant models of human AML disease, Dr. Chan demonstrated that ABT-199 has activity against the leukemic stem cells which are responsible for disease relapse in patients. Finally, he showed that the sensitization effect is likely due to inhibition of a specific enzyme complex in the mitochondrial electron transport chain by 2-hydroxyglutarate, the oncometabolite that is generated by the mutant IDH enzymes. 

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