Research Interests

Phosphatidylinositol Metabolism and Functions

Phosphatidylinositol can be phosphorylated in various combinations on three positions of the inositol ring. This generates 8 possible molecules, each of which may have important roles in the regulation of intracellular events. A major focus of my research is study of the metabolism and roles of these lipids, especially PI3P Imagephosphatidylinositol-3-phosphate and phosphatidylinositol-3,5-bisphosphate (see schematic).

In 2007 we reported that insulin can stimulate the production of PI(3)P at the plasma membrane of 3T3-L1 adipocytes. We also described a novel small GTPase cascade which regulates the synthesis of this lipid in response to insulin. cascade Since then we have been examining the metabolism of PI(3)P and its role in insulin signaling.

Regulation of Intracellular Trafficking

One aspect of phosphatidylinositol and small GTPase dependent cellular regulation is the co-ordination of intracellular trafficking events. Our laboratory is particularly interested in the transport of the facilitative glucose transporter GLUT4 to the plasma membrane in response to insulin. This transmembrane shuttle is normally stored in intracellular compartments, and in response to insulin undergoes regulated exocytosis to the plasma membrane where it can allow uptake of glucose into fat and muscle.

Following up on our identification of the novel small GTPase regulators of GLUT4 trafficking (Rab31 and Rab5) and the potential role of PI(3)P in GLUT4 exocytosis, we are screening for possible potential modulators of GLUT4 trafficking in mammalian cells. In addition to this, we are examine the role of both gain and loss of function phenotypes of these lipids on the transport of GLUT4.

Metabolism and Nutrient Homeostasis

A third major area of interest is the regulation of nutrient storage in muscle, fat and liver tissue. Insulin promotes the increase storage of blood glucose as glycogen or lipid in these tissues, with similar though not totally conserved mechanisms.

I am interested in the mechanisms of signal transduction, or the ways in which the insulin signal is propagated to have effects on primary metabolism. I am examining the mechanisms by which insulin and other anabolic stimuli promote post-translational and transcriptional changes in these cell types, which result in altered nutrient storage.