Robert Hardy, PhD

hardyAssociate Professor

Dept. of Pathology

Contact Information:

Office Address: LHRB 531
Phone: 205-934-9925
E-mail: rwfh1@uab.edu
Websites: School of Medicine Faculty Profile

Education:

University of Waterloo, Canada
BSc, Biology and Chemistry, 1975

University of Toronto, Canada
MSc, Clinical Biochemistry, 1982

University of Toronto, Canada
PhD, Clinical Biochemistry, 1988

Post-Graduate Training:

Washington University, St. Louis, MO
Postdoctoral Fellow, Diabetes, 1988-90

University of Alabama at Birmingham
Postdoctoral Fellow, Diabetes, 1990-1

Research Description:

My primary area of interest is to understand how individual fatty acids affect disease processes at the cellular and molecular level. In particular I am interested in cancer cell metastasis. Cancer cell metastasis: The Ras superfamily of small GTPases control a wide range of cellular processes by switching between inactive GDP- and active GTP-bound states. These active proteins regulate cell behavior by binding to effector molecules and changing their location, activity and protein-protein interactions. Mutated versions of the Ras genes were first identified in human cancers over 20 years ago. The importance of aberrant Ras activation in oncogenesis is well established. Members of both the Ras and Rho subfamilies are known to affect cell proliferation. More recently it has been suggested that Ras and Rho signaling pathways crosstalk in such a way as to favor transformation and cell proliferation. Exactly how these two Ras superfamily members communicate is not entirely clear. One recent study indicated that in NIH 3T3 cells oncogenic Ras activates RhoA by inhibiting Ras induced p190Rho-GAP sequestration in a detergent resistant membrane (DRM) fraction. We have demonstrated that the long chain saturated fatty acid, stearate (C18:0), found in meat and chocolate, inhibits epidermal growth factor induced breast cancer cell proliferation. More recently we have show that this inhibition of cell proliferation is accompanied by an arrest of the cell cycle, an increase in Ras activity and a decrease in Rho activity. We are interested in pursuing the mechanism whereby stearate stimulates Ras activity and yet inhibits Rho activity. In addition we are also interested in determining whether dietary stearate inhibits Ras mediated breast cancer tumor formation in vivo. The importance of these studies is that this is the first mechanistic evidence of a nutrient interfering with Ras-Rho crosstalk and may represent a novel dietary approach to inhibition of cancer progression.

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