One of our research interests is to define all essential and potentially 'druggable' survival genes required by myeloma tumor cells. We are attempting to do this by conducting large-scale RNA interference genetic screens in a range of myeloma cells using pooled lentivirus libraries containing 80,000+ shRNA targeting the genome. To capture the genetic heterogeneity of myeloma tumors in our results, we are screening a panel of hypo- or hyper-diploid tumor lines bearing common t(4;14), t(11;14) or t(14;16) translocations and 13q or 17p deletions. Previously, we have used smaller scale RNA interference studies, including a 17,000 siRNA screen, to identify critical Achilles heel vulnerabilities within a portion of the genome in myeloma cells. A second research interest is to identify molecular targets within the genome whose inhibition synergistically sensitizes myeloma cells to the most potent anti-myeloma drugs currently available, in order to guide development of highly synergistic drug combination strategies for patients. In parallel we aim to identify all genes whose loss is associated with drug protection, in order to investigate drug resistance mechanisms. A third research goal is the evaluation of critical molecular vulnerabilities within myeloma tumor cells as prospective drug targets, using various experimental models. To short-list genes for evaluation we are combining various 'omics' datasets to determine the role of critical tumor genes in promoting myeloma development and progression and to identify molecular targets that may be selectively vulnerable in myeloma cells.
Princess Margaret Cancer Center:
610 University Ave, Toronto, ON M5G 2C4, Canada
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