Project 174085

Epithelial mesenchymal transdifferentiation (EMT) is a ubiquitous biological process seen in development, metastatic transformation of cancer, and fibrosis. I hypothesize that EMT consists of a series of biological 'modules' and each of these 'modules' (epithelial release, migration, and invasion) is induced by different factors and involve different and redundant signaling pathways. The research outlined in this proposal will use in vivo models of fibrosis associated EMT to further our understanding of this essential biological process. In these experiments, I will induce peritoneal fibrosis using adenovirus mediated gene transfer of growth factors. This will be combined with small molecule kinase inhibitors and transgenic animals where key signal transduction elements are knocked out or inhibited. These methods will allow us to analyze in vivo signaling pathways in EMT, to understand this process in greater detail, and to develop targets for future therapeutic intervention. I see that this research will impact patients reliant on peritoneal dialysis as we develop strategies to prevent peritoneal membrane injury, but will also be important for patients with a variety of diseases marked by fibrosis - progressive renal failure, liver cirrhosis, and idiopathic pulmonary fibrosis.