The goal of our research is to understand the molecular mechanisms of Hedgehog (Hh) signal transduction and the roles of Hh signaling components in development and cancer. We focus on the regulation of Smoothened (Smo), a seven-span transmembrane protein required for transduction of the Hh signal in cells exposed to the Hh ligand. We have been investigating novel mechanisms that are critical in mediating the activation of Smo.