Dr. Chan received his medical and research training at Stanford University in California where he earned his MD and PhD degree in Immunology. He completed his internal medicine residency and adult hematology fellowship 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.
The overall goals of Dr. Chan’s research program are: 1) to determine the metabolic requirements for the maintenance of self-renewing leukemic stem cells; and 2) to discover novel therapeutic strategies that target their unique metabolic vulnerabilities.

Given the central role of the mitochondria in a multitude of cellular processes, his laboratory will primarily focus on the role of this organelle in leukemogenesis. His research will attempt to address the following fundamental questions:
  1. What are the differences in metabolic and mitochondrial properties between leukemic stem cells (LSCs) and more differentiated non-LSCs?
  2. How do nuclear or mitochondrial DNA mutations contribute to these changes in LSCs?
  3. How do these changes contribute to leukemogenesis and stemness in LSCs?
The laboratory will employ a range of advanced genetic and analytical tools to study these questions in human-derived AML samples in ex vivo cultures and in xenotransplant models (e.g., NSG mice).

Another focus of the lab is to develop novel therapies that target the mitochondria. Recent studies have shown fundamental differences in mitochondrial properties between LSCs and normal HSCs. These differences can potentially be exploited for therapeutic purposes. Dr. Chan's laboratory will employ shRNA and CRISPR/Cas9-based genetic screens to identify unique vulnerabilities associated with mitochondrial dysfunction in leukemic cells. In addition, these screens will be used to identify potential drug partners that overcome resistance to existing mitochondria-targeted drugs (e.g., BCL-2 inhibitors). 
 
Sci Transl Med. 2019 Oct 30;11(516):
Sharon D, Cathelin S, Mirali S, Di Trani JM, Yanofsky DJ, Keon KA, Rubinstein JL, Schimmer AD, Ketela T, Chan SM
Blood Adv. 2019 Aug 13;3(15):2307-2311
Murphy T, Zou J, Daher-Reyes GS, Arruda A, Gupta V, McNamara CJ, Minden MD, Schimmer AD, Sibai H, Yee KWL, Korulla M, Stockley T, Kamel-Reid S, Maze D, Tierens A, Bratman SV, Schuh AC, Chan SM
Am J Hematol. 2019 Apr 03;:
Medeiros BC, Chan SM, Daver NG, Jonas BA, Pollyea DA
Leuk Res. 2018 Feb 20;68:22-28
Kavanagh S, Heath E, Hurren R, Gronda M, Barghout SH, Liyanage SU, Siriwardena TP, Claudio J, Zhang T, Sukhai M, Stockley TL, Kamel-Reid S, Rostom A, Lutynski A, Khalaf D, Rydlewski A, Chan SM, Gupta V, Maze D, Sibai H, Schuh AC, Yee K, Minden MD,...
Cancer Discov. 2017 Oct;7(10):1136-1153
McKeown MR, Corces MR, Eaton ML, Fiore C, Lee E, Lopez JT, Chen MW, Smith D, Chan SM, Koenig JL, Austgen K, Guenther MG, Orlando DA, Lovén J, Fritz CC, Majeti R
Leukemia. 2017 Apr;31(4):798-807
Heath EM, Chan SM, Minden MD, Murphy T, Shlush LI, Schimmer AD
Oncotarget. 2016 Nov 29;7(48):79722-79735
Matre P, Velez J, Jacamo R, Qi Y, Su X, Cai T, Chan SM, Lodi A, Sweeney SR, Ma H, Davis RE, Baran N, Haferlach T, Su X, Flores ER, Gonzalez D, Konoplev S, Samudio I, DiNardo C, Majeti R, Schimmer AD, Li W, Wang T, Tiziani S, Konopleva M
Oncotarget. 2016 Nov 15;7(46):74917-74930
Huang M, Garcia JS, Thomas D, Zhu L, Nguyen LX, Chan SM, Majeti R, Medeiros BC, Mitchell BS

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Staff Physician, Princess Margaret Cancer Centre
Assistant Professor, Division of Hematology, Department of Medicine, University of Toronto