Ph.D., Case Western Reserve University, 1996
I am interested in understanding how integrins and integrin-mediated signaling contribute to the late stages of carcinoma progression where cells acquire the ability to invade into the surrounding tissues. Integrin receptors, which link the extracellular matrix to the cytoskeleton and various signaling pathways, are essential for cells to sense and integrate cues from the extracellular matrix. Signaling from integrin receptors is critical for carcinoma cell invasion. One integrin species, the α6β4 integrin, can promote this process. My work has uncovered a link between integrin signaling and cyclic AMP metabolism. The metabolism of cAMP, i.e. both its generation and breakdown, is delicately balanced during invasion and is required for the control of the Rho family of small GTPases. We also find that the α6β4 integrin can promote the expression of pro-invasive genes, such as autotaxin, S100A4 and EGFR ligands amphiregulin and epiregulin. My long term goal is to understand the how integrins and integrin signaling control cAMP metabolism, RhoA, gene transcription and autocrine secretion to thereby contribute to the aggressive behavior of advanced cancers, including carcinomas of the breast, colon and pancreas.