Igor Stagljar, of the University of Toronto, will deliver a seminar entitled, "Receptor Tyrosine Kinase-Interactomes, Drug Action & Genome-Informed Medicine." Hosted by Lara Mahal.
For the speaker's page, click here.
During tumor progression, cancer cells acquire characteristic features, due to signaling pathways that significantly differ compared to normal cells. These pathways involve numerous membrane proteins that transmit signals via tightly regulated protein-protein interactions (PPIs), resulting in conversion of signals into a biological response. Understanding how these signaling networks function in vivo and how they are altered in cancer represents a major scientific challenge crucial to the development of new cancer therapies. However, since membrane proteins are extremely difficult to study using current genomics technologies due to their complex biochemical features, research into this area has lagged behind, with membrane proteins screened to a significantly lower degree than other protein classes.
During my talk, I will report on our previously developed cell based high-throughput proteomics screening technology, called the Mammalian Membrane Two-Hybrid (MaMTH) assay and its application to dissect signaling pathways in normal and cancer cells. In addition, I will discuss how our recent application of MaMTH to various human Receptor Tyrosine Kinases (RTKs), an important family of membrane proteins involved in the variety of cell signaling processes, identified several novel therapeutically important interactors of these RTKs of a therapeutical importance. Lastly, I will also demonstrate how MaMTH can efficiently be used as a drug discovery assay for identification of inhibitory compounds that change the phosphorylation status of the human Epidermal Growth Factor Receptor (EGFR) in the context of living cells and in the low nanomolar range, an advance which may open up a whole new approach to drug development and lead to more effective treatments for lung cancer patients.