Research
The overall goal of my research program will be to utilize biophysical methods to understand signaling events in cells, particularly proteins that interact with lipids in disease states, by employing proteomic, kinetic, and biophysical techniques for the manipulation of signaling pathways/effects. The end result will be a collection of new targets for drug discovery. The central question of my research program can be surmised as: how can we modulate membrane protein interactions with lipids thereby affecting signaling events? My research program would bring a unique expertise to your department, small angle scattering, which could be used to study globular structures as well as conformational changes related to functional interactions.

The current research interest revolves around studying the molecular basis through which Amot ACCH domains associate with membrane surfaces and therefore establish the link between Amot control of cellular polarity and cellular proliferation and migration. The Amot family of adaptor proteins directly integrate the signaling that controls cellular differentiation and cell growth (Wells, Fawcett et al. 2006; Ranahan, Han et al. 2011; Zhao, Li et al. 2011). Amot family members directly bind the core polarity proteins that control the organization of the apical domain of epithelial cells as well as Yap, a transcriptional co-activator that appears to be the key factor in cell growth regulation (Wells, Fawcett et al. 2006; Zhao, Li et al. 2011). An essential property of all Amot proteins is a domain that preferentially binds phosphoinositol lipids (ACCH domain) and is predicted to be conserved in all metazoans (Heller, Adu-Gyamfi et al. 2010). This study defines the biophysical properties that govern the binding of the Amot ACCH domain to phosphoinositol lipids in membranes, and the consequential effects on membrane deformation and vesicle joining (aggregation or fusion). By coupling structural and in vitro biophysical studies of specific domains and protein-lipid interactions, we learn how the protein specifically recognizes and reorganizes cellular membranes.