Clinical Studies Resource Centre Member Ontario Cancer Institute (OCI)
Keywords: translational research, leukemia, apoptosis, drug discovery, high throughput screening, caspases
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 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 trial.