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.
The thymidine dideoxynucleoside analogue, alovudine, inhibits the mitochondrial DNA polymerase γ, impairs oxidative phosphorylation and promotes monocytic differentiation in acute myeloid leukemia.
Haematologica. 2018 Dec 20;:
Support Care Cancer. 2018 Dec 08;:
Nat Commun. 2018 Dec 03;9(1):5132
Cancer Cell. 2018 Nov 12;34(5):695-696
Octadecyloxyethyl Adefovir Exhibits Potent in vitro and in vivo Cytotoxic Activity and Has Synergistic Effects with Ara-C in Acute Myeloid Leukemia.
Chemotherapy. 2018 Oct 29;63(4):225-237
Oncotarget. 2018 Sep 28;9(76):34198-34199
A phase II open-label study of aprepitant as anti-emetic prophylaxis in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy.
Support Care Cancer. 2018 Oct 19;:
The mutational landscape of accelerated- and blast-phase myeloproliferative neoplasms impacts patient outcomes.
Blood Adv. 2018 Oct 23;2(20):2658-2671
The Experience of Medical Communication in Adults with Acute Leukemia: Impact of Age and Attachment Security.
Psychooncology. 2018 Oct 12;:
Acyldepsipeptide Analogs Dysregulate Human Mitochondrial ClpP Protease Activity and Cause Apoptotic Cell Death.
Cell Chem Biol. 2018 Aug 16;25(8):1017-1030.e9
Senior Scientist, Princess Margaret Cancer Centre
Professor, Department of Medical Biophysics, University of Toronto
Staff Physician, Leukemia Site Group, Princess Margaret Cancer Centre