Department of Biological Sciences
University of Delaware
320 Wolf Hall
Newark DE 19716-2590
Phone: (302) 831-2669
Fax: (302) 831-8922
Postdoc, University of Michigan, 1999
Ph.D., University of Texas, Health Science Center, 1996
B.A., Michigan State University, 1987
The Rho GTPases comprise a group of 23 small GTP binding proteins that play a significant role in nearly every cellular process. One of the most characterized roles of the Rho proteins is their ability to reorganize the cell cytoskeleton. Signals from the extracellular environment, transduced through growth factor receptors and/or cell adhesion molecules leads to the coordinated activation of Rho proteins and reorganization of the cytoskeleton. In turn, this leads to changes in cells shape, polarity, migratory and invasiveness.
The potent ability of the Rho proteins to affect cell migration and invasion has many implications for the dissemination and spread of cancer and in normal processes such as development and immunity. Our primary interest is in the role of the Rho GTPases in conferring the metastatic phenotype to aggressive cancers.
In 1999 our laboratory found that RhoC GTPase, one member of the Rho family, was overexpressed in inflammatory breast cancer, a particularly aggressive form of breast cancer which spreads rapidly through the dermal lymphatics of the breast. Later, we found that RhoC over expression was a prognostic marker for metastasis in small breast tumors (<1 cm in size). Since then we have begun to look at how RhoC confers a metastatic phenotype to inflammatory breast cancer and how it interacts with other Rho GTPases. Our studies have expanded to include pancreatic cancer and prostate cancer bone metastasis.
A complete understanding of how the Rho proteins, particularly RhoC, can influence progression of a cancer cell to become metastatic is key to the development of anti-metastatic therapies. To facilitate this we have developed a RhoC transgenic mouse. This mouse has a tumor phenotype but more interestingly it has a neurological phenotype which is yet undetermined. Our ultimate goal is to detail the Rho pathways, determining the choke points and developing inhibitors that can be used as adjuvant anti-metastatic therapies.