The regulatory processes underlying the transformation of epithelium to mesenchyme in embryonic development and cancer are not well understood. Cell transformation is mediated by cell-cell interactions between different tissues and the signaling between tissues is mainly through growth factors and cell adhesion molecules. Growth factors activate signal transduction pathways and initiate gene expression cascades that result in the change in phenotype, such as changes in the cadherin family of cell-cell adhesion molecules. Intercellular communication maintains tissue homeostasis through tightly balanced regulation of cell survival and cell growth.
Our studies have focused on the roles of cadherins and catenins in the transformation of epithelium to mesenchyme during progression of prostate cancer, and in the differentiation of mesenchymal cells from endothelium to form heart valves. Common signaling pathways are shared in cell transformation during metastasis and transformation of cardiac endothelial cells into mesenchyme of the valves and walls of the heart. In prostate carcinoma progression, we described a switch from E-cadherin to N-cadherin, which is linked to malignancy. Identification of the role of cadherins and characterization of the mechanisms for their contribution to metastasis is one important area of prostate cancer research because these studies are generating information for the improvement of diagnosis and therapy of prostate cancer. Thus, exploring mechanisms for N-cadherin mediated gene expression program is to understand the molecular mechanisms signaling in malignant prostate carcinoma. This may explain in part one of the crucial steps to metastasis, a fundamental concept in cancer biology, which has yet to be explained at the molecular level. An additional research focus is on the Pathogenesis of Vascular Occlusive Disease. Blood vessels are dynamic structures, being able to make rapid and lasting changes in vessel structure and function and our research is using molecular cellular and genetic approaches to investigate SMC cadherins in critical roles of cell-cell adhesion and cell signaling during neointima formation by SMCs.