Professor  |  Staff Physician and Scientist

Aaron Schimmer

MD, PHD, FRCPC

Location
Princess Margaret Cancer Research Tower
Address
101 College St, Room 8-706, Toronto, Ontario Canada M5G 1L7
Research Interests
Cancer Diagnosis and Therapy, Cancer Mechanisms and Models, Stem Cells and Regenerative Medicine

Research Synopsis

Chemical Biology and Drug discovery

Our lab is interested in developing new therapeutic strategies for AML (acute myeloid leukemia) that effectively target leukemic stem cells. Using genetic and chemical approaches, including high throughput screens, we identify biological vulnerabilities in the AML cells and stem cells with a focus on mitochondrial and metabolic pathways. Through these efforts, we discover new biological pathways important for the growth and viability of AML and highlight new therapeutic approaches for this disease.


Recent Publications

  • Skrtic M, Sriskanthadevan S, Jhas B, Gebbia M, Wang X, Wang Z, Hurren R, Jitkova Y, Gronda M, Maclean N, Lai CK, Eberhard Y, Bartoszko J, Spagnuolo P, Rutledge AC, Datti A, Ketela T, Moffat J, Robinson BH, Cameron JH, Wrana J, Eaves CJ, Minden MD, Wang JC, Dick JE, Humphries K, Nislow C, Giaever G, Schimmer AD. Inhibition of mitochondrial translation as a therapeutic strategy for human acute myeloid leukemia. Cancer Cell. 2011;20:674-88.
  • Cole A, Wang Z, Coyaud E, Voisin V, Gronda M, Jitkova Y, Mattson R, Hurren R, Babovic S, Maclean N, Restall I, Wang X, Jeyaraju DV, Sukhai MA, Prabha S, Bashir S, Ramakrishnan A, Leung E, Qia YH, Zhang N, Combes KR, Ketela T, Lin F, Houry WA, Aman A, Al-Awar R, Zheng W, Wienholds E, Xu CJ, Dick J, Wang JC, Moffat J, Minden MD, Eaves CJ, Bader GD, Hao Z, Kornblau SM, Raught B, Schimmer AD. Inhibition of the Mitochondrial Protease ClpP as a Therapeutic Strategy for Human Acute Myeloid Leukemia. Cancer Cell. 2015;27:864-76.
  • Sriskanthadevan S, Jeyaraju DV, Chung TE, Prabha S, Xu W, Skrtic M, Jhas B, Hurren R, Gronda M, Wang X, Jitkova Y, Sukhai MA, Lin FH, Maclean N, Laister R, Goard CA, Mullen PJ, Xie S, Penn LZ, Rogers IM, Dick JE, Minden MD, Schimmer AD. AML cells have low spare reserve capacity in their respiratory chain that renders them susceptible to oxidative metabolic stress. Blood. 2015;125:2120-30.
  • Reed GA, Schiller GJ, Kambhampati S, Tallman MS, Douer D, Minden MD, Yee KW, Gupta V, Brandwein J, Jitkova Y, Gronda M, Hurren R, Shamas-Din A, Schuh AC, Schimmer AD. A Phase 1 study of intravenous infusions of tigecycline in patients with acute myeloid leukemia. Cancer Med. 2016;5:3031-40.
  • Rotin LE, MacLean N, Aman A, Gronda M, Lin FH, Hurren R, Wang X, Wrana JL, Datti A, Al-Awar R, Minden MD, Schimmer AD. Erlotinib synergizes with the poly(ADP-ribose) glycohydrolase inhibitor ethacridine in acute myeloid leukemia cells. Haematologica. 2016;101:e449-e53.
  • Liyanage SU, Hurren R, Voisin V, Bridon G, Wang X, Xu C, MacLean N, Siriwardena TP, Gronda M, Yehudai D, Sriskanthadevan S, Avizonis D, Shamas-Din A, Minden MD, Bader GD, Laposa R, Schimmer AD. Leveraging increased cytoplasmic nucleoside kinase activity to target mtDNA and oxidative phosphorylation in AML. Blood. 2017;129:2657-66.
  • Seneviratne A, Xu M, Aristizabal Henao J, Fajardo V, Hao Z, Voisin V, Wei G, Hurren R, Kim S, MacLean N, Wang X, Gronda M, Jeyaraju D, Jitkova Y, Ketela T, Mullokandov M, David S, Thomas G, Chouinard-Watkins R, Hawley J, Schafer C, Loo Yau H, Khuchua Z, Aman A, Al-awar R, Gross A, Claypool S, Bazinet R, Lupien M, Chan S, De Carvalho D, Minden M, Bader G, Stark K, LeBlanc P, Schimmer AD. The mitochondrial transacylase, Tafazzin, regulates AML stemness and differentiation by modulating intracellular levels of phospholipids. Cell Stem Cell, Mar 2019 in press
  • Ishizawa J *,Zarabi SF *, Davis RE, Halgas O, Nii T, Jitkova Y, Zhao R, St-Germain J, Heese LE, Egan G, Ruvolo VR, Barghout SH, Nishida Y, Hurren R, Ma W, Gronda M, Link T, Wong K, Mabanglo M, Kojima K, Borthakur G, MacLean N, Ma MCJ, Leber AB, Minden M, Houry W, Kantarjian H, Stogniew M, Raught B, Pai EF, Schimmer AD, Andreeff M. Mitochondrial ClpP-mediated proteolysis induces selective cancer cell lethality. Cancer Cell, Mar 2019 in press

Graduate Students

Samir Barghout
Aaron Botham
Sarah Zarabi