Project 443704

In Western societies, ~45% of deaths, including certain types of invasive cancers, heart failure, and chronic kidney disease, are associated with disorganized connective tissues and loss of their normal function in a process that is called fibrosis. This widespread disorder has important implications for human health but it is not known how cells, when disrupted by disease, cause fibrosis to occur. It is also not understood how normal cell function leads to alterations of the protein structures of supporting tissues. In this proposal we have identified a new signaling system that appears to be an important contributor to the generation of fibrosis in tissues. This system is driven by the interplay between two proteins in cells in a manner that was recently discovered by us. We hope to examine how the interplay between these proteins causes fibrosis and how the interplay might be interrupted as a potential anti-fibrotic treatment.