Steven Chan

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). 
 
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
Leukemia. 2017 Feb;31(2):272-281
Medeiros BC, Fathi AT, DiNardo CD, Pollyea DA, Chan SM, Swords R
Nat Genet. 2016 Oct;48(10):1193-203
Corces MR, Buenrostro JD, Wu B, Greenside PG, Chan SM, Koenig JL, Snyder MP, Pritchard JK, Kundaje A, Greenleaf WJ, Majeti R, Chang HY
Cell Stem Cell. 2015 Dec 3;17(6):675-88
Mazumdar C, Shen Y, Xavy S, Zhao F, Reinisch A, Li R, Corces MR, Flynn RA, Buenrostro JD, Chan SM, Thomas D, Koenig JL, Hong WJ, Chang HY, Majeti R
Semin Hematol. 2015 Jul;52(3):150-64
Reinisch A, Chan SM, Thomas D, Majeti R
Nat Med. 2015 Feb;21(2):178-84
Chan SM, Thomas D, Corces-Zimmerman MR, Xavy S, Rastogi S, Hong WJ, Zhao F, Medeiros BC, Tyvoll DA, Majeti R
Blood. 2015 Jan 8;125(2):316-26
Sinha S, Thomas D, Yu L, Gentles AJ, Jung N, Corces-Zimmerman MR, Chan SM, Reinisch A, Feinberg AP, Dill DL, Majeti R

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