GRAVES LAB
BRIAN J. DEWAR
BACKROUND:
Undergraduate: Geneva College, Beaver Falls, PA, B.S. in Biology (Chemistry, minor), 1998.

Work Experience: Jananuary 1999-June 2001: Research Laboratory Technician Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, University of North Carolina at Chapel Hill, NC.; Director – Dr. Ronald G. Thurman.


RESEARCH INTERESTS: Modulation of PTEN protein stability after extracellular exposure of zinc

RESEARCH SUMMARY
Phosphatase and tensin homologue deleted on chromosome ten (PTEN) is a dual specificity phosphatase whose main cellular function is the dephosphorylation of phosphatidyl-inositol-3,4,5- trisphosphate (PIP3) to phosphatidyl-inositol-4,5-bisphosphate (PIP2). PTEN directly antagonizes the phosphatidylinositol 3-kinase (PI3K)/ AKT pathway through the de-phosphorylation of PIP3. Activation of PI3K primarily by growth factors leads to the generation of PIP3, a key second messenger in the activation of AKT. Phosphorylation of downstream targets by AKT prevents apoptosis and promotes cell survival. Recent data have shown that following extracellular treatment of zinc, PTEN is degraded via an ubiquitin and proteosome dependent pathway. Moreover, inhibition of PI3K with LY294002 effectively prevented the loss of PTEN protein after zinc treatment, suggesting that changes in PTEN phosphorylation regulate protein stability. Numerous studies have shown that several C-terminal residues of PTEN are phosphorylated and critical for protein stability. My research focuses on the mechanisms that regulate PTEN protein stability following exposure of cells to zinc.


PUBLICATIONS