Grant: Project Grant

We study the regulation of protein synthesis in normal and cancer cells. Making proteins is the most energy-consuming process in a cell and there are a number of checkpoints for controlling this critical event. This regulation is disrupted in cancer cells to help fuel cancer initiation and progression and has also been associated with resistance to chemotherapy. To date, we understand very little of how unregulated protein synthesis leads to tumorigenesis, and whether it is the over-production of some or many proteins that is responsible for this. The goal of my research is to address these issues and determine how to capitalize on this information for drug development purposes. In search of drugs to block this process in cancer cells, my lab has screened over 700,000 compounds for novel inhibitors. This effort was quite successful in identifying six compounds that block protein synthesis in tumor cells, with several of these showing selective cancer cell killing. These compounds have been very important in demonstrating that tumor cells are dependent on elevated protein synthesis for their survival and providing proof-of-concept for targeting this process as an anti-cancer approach. We have shared these unique reagents with >85 labs worldwide. The proposed research program builds on our expertise in this area and aims to better understand the fundamental process of protein synthesis in normal and cancer cells and define the mechanism of action of our potent anti-cancer compounds. Our research uses a multi-disciplinary approach, combining chemistry expertise with the power of molecular biology and cutting-edge pre-clinical cancer models. It is forged on strong international collaborations with labs that bring complementary expertise, colleagues in the Pharmaceutical industry to ensure our end-goals are correctly aligned with drug discovery objectives, and oncologists to ensure appropriate clinical needs are addressed.