The overarching current focus of our work is the basic cell and molecular biology of organ fibrosis. We are interested in the role of the cytoskeleton – as a cell fate-determining device – in regulating cellular structure and function, including gene expression, intercellular contacts, the process of epithelial-mesenchymal transition (EMT) and the development of profibrotic epithelial phenotype (PEP). We study the nuclear transport of fibrogenic and mechanosensitive transcription factors (MRTF, TAZ, YAP), and the role and regulation of these proteins in various disease entities (e.g. kidney fibrosis, polycystic kidney disease, etc). We also investigate the effect of cytoskeletal changes and the associated signaling on organellar structure/function, including the remodeling of mitochondria and the primary cilium. The studies are organically linked to our previous and continuing interest in cellular stress signaling, particularly as pertains to pH and volume regulation (e.g. osmotic stress). Taken together our studies have a dual aim: to understand fundamental mechanisms underlying structure-dependent regulation of normal and pathologic cellular functions, and to explore key cellular evets whereby these processes contribute to the pathogenesis of organ fibrosis, a major and silent killer (45% of all death), affecting all organ systems.
