Research Interests:The discovery of retroviral oncogenes in the 1970’s lead to the identification of their corresponding normal cellular proto-oncogene homologs. Their encoded proteins were subsequently found to play important signalling functions controlling cellular survival, growth, proliferation and differentiation.It seemed that mutations leading to over exuberant or altered activity of these oncoproteins could be at the root of cancer, and perhaps many other diseases. The pharmaceutical industry descended on these oncoproteins with drug discovery programs aimed at developing targeted small molecule inhibitor based therapeutics. We appeared on the verge of cures or clinical management of several major cancers and other diseases.However, with a few exceptions, essentially all targeted small molecule inhibitors have failed cancer clinical trials when used as single agents.Much like the organisms in which they develop, cancer cells are willey creatures capable of evolving to survive in face of seemingly insurmountable challenges. This often leads to cancer relapse after what often appears to be a successful clinical intervention. It is clear that we need to devise more ingenious multipronged attacks to prevent cancer relapse.
Our research explores several potential therapeutic targets, but it considers these in the context of the larger picture of mitogenic and survival signalling pathways available to the cancer cell.We reason that targeted inhibition of one pathway will select for cancer cells that have evolved to bypass that first pathway, perhaps by engaging alternative parallel or interacting pathways.It follows that we must anticipate this plasticity in the signalling apparatus of the surviving cancer cells and use an appropriate combination of targeted small molecule inhibitors which collectively prevent survival of all cancer cells.
Current projects in the lab explore the functions of Fps/Fes and Fer protein-tyrosine kinases and the calpain protease system in cellular signalling.We also investigate the effects of single or combinations of small molecule kinase inhibitors on the signalling apparatus of cancer cells. This work involves biochemistry, molecular biology, cell biology, transgenic and gene knock-out mice and animal physiology, and translational cancer research using clinical materials.