Rho GTPases control signal transduction pathways linking plasma membrane receptors to the spatially organized assembly of filamentous actin. In addition, they promote a diverse set of other cellular activities, including gene transcription, cell polarity, cell cycle progression, microtubule reorganization, and the allosteric regulation of enzymes such as PI-3kinase and NADPH oxidases.
Changes in the actin cytoskeleton drive many dynamic aspects of cell behavior, for example associated with migration, morphogenesis, axon guidance, phagocytosis, endocytosis and cell division.
Our particular focus is on the mechanisms by which Rho GTPases regulate epithelial cell migration and morphogenesis. We are using two human cell lines: 16HBE derived from airway epithelium, which establish apical basal polarity and tight junctions in 2D yet undergo collective migration, and Caco-2 derived from colonic epithelium, which form polarized cysts in 3D.
The disruption of normal tissue architecture and the appearance of inappropriate migratory activity are two defining characteristics associated with cancer progression towards an invasive/metastatic phenotype. Our goal is to identify the mechanisms that drive these changes in epithelia