Cell Signalling and Proteomics

Our main interest is to understand how mitogens and oncogenes regulate cell growth and proliferation. We focus our research on signal transduction pathways often deregulated in metabolic diseases and cancer, including the Ras/ERK and PI3K/mTOR signaling cascades.

The Ras/ERK signaling pathway is activated by many growth factors and controls essential biological processes, including cell cycle progression, cell differentiation, survival and motility. Proper regulation of this pathway is crucial as activating/inactivating mutations within this cascade lead to various genetic disorders and diseases, including cancer. Indeed, activating mutations in Ras and Raf are found in about 30% of all human cancers and are particularly common in pancreatic (90%), colon (50%), thyroid (45%) and skin (63%) cancers. Based on the well-defined role for the Ras/ERK pathway in human cancers, therapeutic targeting has been an area of intense investigations. The RSK family of protein kinases is directly activated by Ras/ERK signaling and has been reported to act as an important effector of this pathway. An important objective of our laboratory is to understand the regulation of RSK activity by oncogenes and mitogens, and to elucidate the biological significance of these proteins with regards to cellular growth control.

The mammalian target of rapamycin (mTOR) is a conserved Ser/Thr kinase that regulates cell growth as well as organ and body size in a variety of organisms. mTOR was discovered as the molecular target of rapamycin, an antifungal agent used clinically as an immunosuppressant and more recently, as an anti-cancer drug. Emerging evidence indicates that deregulation of the PI3K and mTOR pathways occurs in many types of cancer, underscoring the importance of understanding how these pathways are regulated by oncogenic and mitogenic cues. We have found that Ras/ERK signaling positively regulates mTOR activity, and one of our goals is to characterize the molecular mechanisms underlying this important regulation.

Our experimental approaches include a combination of mouse genetics, molecular and cellular biological methods. Our interest in cellular processes regulated by phosphorylation events also involves the use of cutting-edge proteomics technologies. As the Ras/ERK and PI3K/mTOR pathways represent attractive molecular targets for cancer therapies, a better understanding of these signaling cascades will be required to determine the roles they play when a cell becomes cancerous or otherwise takes the wrong path.

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