Our lab is focused on developing novel therapeutic strategies that target leukemia and leukemia stem cells. Using chemical and genetic approaches, our laboratory investigates targeting protein synthesis and degradation pathways in the mitochondria and cytoplasm. Mechanistic studies are coupled with preclinical evaluation to understand the biology of leukemia stem cells and highlight therapeutic strategies with potential therapeutic windows. In addition to acting as biological tools, these molecules also serve as leads for potential new treatment strategies. For example, using these approaches, we have demonstrated that acute myeloid leukemia (AML) cells and stem cells have a unique reliance on mitochondrial metabolism and have heightened sensitivity to inhibitors of mitochondrial translation. We have also demonstrated increased lysosomal mass in AML cells and increased sensitivity to lysosome disruption in this disease. To rapidly identify and test new therapeutic strategies in early proof-of-principle clinical trials, the Schimmer lab has also advanced compounds directly from the lab into Phase I clinical trials.
Acyldepsipeptide Analogs Dysregulate Human Mitochondrial ClpP Protease Activity and Cause Apoptotic Cell Death.
Cell Chem Biol. 2018 Aug 16;25(8):1017-1030.e9
Cell Stem Cell. 2018 Jul 05;23(1):3-4
Preclinical evaluation of the selective small-molecule UBA1 inhibitor, TAK-243, in acute myeloid leukemia.
Leukemia. 2018 Jun 08;:
J Am Dent Assoc. 2018 Mar 30;:
Leuk Res. 2018 Feb 20;68:22-28
Leuk Res. 2018 Feb 15;67:86-91
Impact of genomic alterations on outcomes in myelofibrosis patients undergoing JAK1/2 inhibitor therapy.
Blood Adv. 2017 Sep 12;1(20):1729-1738
Effect of an Antimicrobial Stewardship Programme on Antimicrobial Utilisation and Costs in Patients with Leukaemia: A Retrospective Interventional Controlled Study.
Clin Microbiol Infect. 2017 Nov 11;:
Aspergillus galactomannan detection in exhaled breath condensate compared to bronchoalveolar lavage fluid for the diagnosis of invasive aspergillosis in immunocompromised patients.
Clin Microbiol Infect. 2017 Sep 29;:
JCI Insight. 2017 Sep 21;2(18):
Senior Scientist, Princess Margaret Cancer Centre
Professor, Department of Medical Biophysics, University of Toronto
Staff Physician, Leukemia Site Group, Princess Margaret Cancer Centre