Faculty Research: Deborah Vestal
Associate Professor
Ph.D., Syracuse University, 1988
B.S., Bowling Green State University
Office: 391 Block Health Science & BO3042
Phone No: 419.383.4134
Email: deborah.vestal@utoledo.edu
Research
My laboratory studies the roles of cytokines in informing physiological changes in both normal and tumor cells. Most of our work has focused on the cellular effects of interferons and, in particular, on the consequences of expression of the interferon-induced proteins of the Guanylate-Binding Protein (GBP) family.
Guanylate-Binding Proteins (GBPs)
The GBPs are members of the dynamin superfamily of large GTPases. Unlike members of the Ras superfamily, these proteins can multimerize and their multimerization is both nucleotide-dependent and accelerates GTP hydrolysis. Some of the GBPs contain C-terminal CaaX sequences that direct isoprenylation. Our recent studies of the murine family member, mGBP-2, show that mGBP-2 induction by IFN-γ in fibroblasts inhibits subsequent activation of Rac by integrins, PDGF, and TNF-α. mGBP-2 mediated inhibition of Rac results in retarded ability of the cells to spread on fibronectin. This inhibition of cell spreading is also accompanied by an inhibition of the activation of PI3-K, during which mGBP-2 binds to the p110 catalytic subunit of PI3-K. The IFN-γ-induced expression of mGBP-2 also inhibits the induction of MMP-9 expression by TNF-α. mGBP-2 facilitates this inhibition by inhibiting both NF-κB promoter binding and Rac activation. Work is currently in progress to delineate the mechanisms by which mGBP-2 inhibits PI3-K, Rac, and NF-κB.
The human GBP, hGBP-1, is part of a gene signature predicting good disease free progression in breast cancer. Work is currently underway to determine how hGBP-1 improves breast cancer survival.