Research Interests

Our laboratory is interested in understanding the cellular processes controlled by reversible phosphorylation. A family of protein kinases and phosphatases (PTPases) play key roles in this regulation. Our studies have focused largely on the PTPases. In addition to studying the structure and function of the PTPases, we have been able to show that the bacteria responsible for the plague harbor a virulence factor, which is the most active PTPases ever described. We are extending these studies to understand the molecular mechanisms of additional bacteria virulence factors and their impact on cellular signal transduction pathways. Recently we studied the tumor suppressor gene PTEN that shares sequence identity with the PTPases. Our laboratory was the first to show that PTEN dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-triphosphate (PIP3). PIP3 activates the protein kinase AKT that plays a critical role in modulating the balance between cell survival and programmed cell death. The loss of the PTEN gene elevates PIP3 levels, leading to constitutive activation by AKT, which stimulates cell survival and in turn leads to oncogenesis. We are also attempting to identify other PTPases, which function in the regulation of phosyphatidylinositol hydrolysis.

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Primary Section

Section 21: Biochemistry