Signal transduction, cancer, insulin, metabolism, T lymphocytes
Extracellular signals generated by diverse stimuli such as nutrients, growth factors, hormones, stress and pathogens trigger a cascade of events from the cell membrane to the nucleus. Our lab is interested in how these signals are coordinated and integrated to evoke a distinct cellular response such as growth, proliferation, differentiation or death. We focus on the interplay between kinases and phosphatases to understand the regulation of cellular signals.
Our current research is focused on the target of rapamycin (TOR) signaling pathway. This signalling pathway is critical for the regulation of growth or cell size. TOR is a protein kinase that regulates cell growth in response to the presence of nutrients or energy sources. It is inhibited by the clinically important drug, rapamycin (used as an immunosuppressant, anti-fungal, to prevent restenosis in coronary stents, and as a potential anti-cancer drug). Our research objective is to determine how the TOR pathway can link nutrient signals to other extracellular or environmental signals to promote growth. Since TOR controls processes in response to an organism's most basic need, ie. nutrients, it has been implicated in ageing and a variety of growth-related diseases. Ultimately, we would like to understand how deregulation of the TOR pathway can lead to diseases such as cancer, diabetes, and immune-related diseases. Our research should provide insights on growth-regulatory mechanisms that could be targeted for development of drugs against these diseases.
TOR is part of two distinct protein complexes TORC1 (TOR complex 1) and TORC2, TORC1 regulates protein synthesis in response to nutrient availability, and thus serves as a temporal controller of growth. TORC2 controls actin cytoskeleton organization and thus regulates spatial aspects of growth. Our goal is to understand the molecular mechanisms involved in TORC signaling particularly how protein phosphatases regulate TORC1 and possibly TORC2 signaling. The TOR complexes and protein phosphatases are highly conserved from yeast to mammals. Therefore our studies address growth signalling mechanisms in both yeast and mammalian cells using a combination of genetic. biochemical. cell and molecular biological techniques.