Aberrant regulation of RAS, RHO and heterotrimeric GTPases is linked to a variety of disease states, including cancer, cardiovascular and neurological disorders. Our lab employs multidisciplinary structural, computational, biophysical, biochemical and cell biology approaches to 1) elucidate how these GTPases recognize regulatory proteins and down stream effector targets 2) how mutations and posttranslational modifications alter GTPase function 3) identify and characterize inhibitors that antagonize aberrant GTPase function in disease.
Cell adhesion proteins
Our laboratory studies cell adhesion proteins, Vinculin and its splice variant Metavinculin, that control cell morphology, motility and force transmission. Deregulation of these proteins results in cardiomyopathies and cancer. Our research efforts have elucidated protein-protein and protein-membrane interactions critical for regulated cell movement and force transduction. Vinculin forms force and directionally-dependent catch bonds with F-actin. Current efforts are focused on understanding the molecular basis and functional consequences of these key force-dependent interactions. We are also investigating how Metavinculin coordinates with Vinculin to control cell adhesion, morphology, motility and force transduction in fibroblasts and chick embryo hearts.