Dr Tiedemann's lab within the Ontario Cancer Institute is focused on the development of novel therapeutic strategies for multiple myeloma from a comprehensive understanding of myeloma tumor biology and myeloma genomics.
Multiple Myeloma is a malignancy of differentiated plasma cells that accounts for 15% of all hematological cancer. Despite recent advances in treatment MM remains incurable at present and is over represented in cancer death rates. Every year approximately 1,300 Canadians die of this disease.
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.
From early siRNA screens we have previously identified G-protein coupled receptor kinase 6 (GRK6) as a tumor-selective drug target in myeloma and are currently collaborating with others at UHN to develop small molecule inhibitors of this kinase for exploration as novel therapeutics.
For research related enquiries:
416-946-4501 ext. 3344
For patient-related or clinical issues:
416-946-4501 ext. 2520