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.
Aaron D Schimmer
A phase I trial of the aurora kinase inhibitor, ENMD-2076, in patients with relapsed or refractory acute myeloid leukemia or chronic myelomonocytic leukemia.
Invest New Drugs. 2016 Jul 12;
Oncotarget. 2016 Jul 6;
The ubiquitin ligase HERC4 mediates c-Maf ubiquitination and delays the growth of multiple myeloma xenografts in nude mice.
Blood. 2016 Jan 29;
Auger electron-emitting (111)In-DTPA-NLS-CSL360 radioimmunoconjugates are cytotoxic to human acute myeloid leukemia (AML) cells displaying the CD123(+)/CD131(-) phenotype of leukemia stem cells.
Appl Radiat Isot. 2015 Dec 18;110:1-7
Leuk Lymphoma. 2016 Jan 6;:1-13
Investigating the synergistic mechanism between ibrutinib and daunorubicin in acute myeloid leukemia cells.
Leuk Lymphoma. 2016 Jan 6;:1-11
Ibrutinib synergizes with poly(ADP-ribose) glycohydrolase inhibitors to induce cell death in AML cells via a BTK-independent mechanism.
Oncotarget. 2015 Nov 27;
Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: 10-colour flow cytometry diagnosis and HyperCVAD therapy.
Am J Hematol. 2015 Nov 30;
Effect of Red Blood Cell Transfusion Dependence on the Natural History of Myeloproliferative Neoplasm-Associated Myelofibrosis.
Clin Lymphoma Myeloma Leuk. 2015 Nov;15(11):e151-6
Oncotarget. 2015 Oct 15;
Senior Scientist, Princess Margaret Cancer Centre
Professor, Department of Medical Biophysics, University of Toronto
Staff Physician, Leukemia Site Group, Princess Margaret Cancer Centre