Department: Molecular Genetics, University of Toronto
Our laboratory has two interests regarding stem cells, the origin and progression of pediatric cancers, and identifying and characterizing the signal transduction pathways regulating the survival, proliferation, differentiation and migration of nervous system stem cells. In the pediatric cancer area, we focus on neuroblastoma, a common fatal cancer of children. We have identified cancer stem cells from patients with neuroblastoma, and use these cells for gene and signaling pathway discovery, and for drug discovery efforts. In collaboration with the Wrana/Dennis screening facility at Mt. Sinai, we have performed high throughput screening with chemical libraries on the neuroblastoma stem cells, and found a number of drugs, one of which will be in clinical trials, that specifically kill neuroblastoma and not normal pediatric stem cells. The mechanism by which these drugs act will provide us with new information of the survival pathways used by cancer stem cells. Our second interest is determining how mutations in signaling proteins and pathways in neural precursor cells perturb neuronal development. With Freda Miller’s lab, we are identifying signaling pathways regulating the fate, survival, and proliferation of precursor cells, and asking whether mice or people with mutations that affect these signaling pathways have developmental or cognitive deficits.