Andras Kapus

Research Synopsis

The major interests of my lab is to understand the cellular and molecular mechanisms underlying cellular plasticity, particularly as it pertains to epithelial-mesenchymal transition (EMT) and myofibroblast formation. These processes play critical roles in wound repair and regeneration and are central to the pathobiology of organ fibrosis, i.e. injury-induced progressive and often fatal scarring of the lung, liver and kidney. Cellular plasticity i.e. the transformation of one cellular phenotype into another is governed by chemical stimuli such as growth factors (e.g. TGFβ) and cytokines, as well as by mechanical inputs such as cell contractility, forces acting on the intercellular contacts or the nucleus and tissue stiffness. We aim at understanding the interplay and the synergy between chemical and mechanical signal transduction in determining cell fate. The cytoskeleton plays a central role in the integration of various fibrogenic inputs. Accordingly, we study how the cytoskeleton is remodeled upon exposure to chemical and mechanical stress conditions (e.g. osmotic stress), and conversely how cytoskeleton remodeling controls major cell functions including gene expression, ion transport, motility and the dynamics of cellular organelles such as mitochondria, nuclei and the primary cilium. One of the central problems in this area is to uncover the mechanisms whereby cytoskeleton remodeling regulates the nucleocytoplasmic traffic of transcription factors (e.g. the Rho GTPase target myocardin-related transcription factor (MRTF) or the Hippo pathway effectors TAZ and YAP), which in turn reprogram gene expression as have fate-determining effects on phenotype. Overall our research addresses the fundamental biology and cellular pathology of injury and repair.