Our research aims to define the molecular control of intracellular membrane transport, focusing on structure and formation of clathrin-coated vesicles, and to establish the role of membrane transport in the immune system during antigen processing and presentation and understand how pathogens and disease affect these pathways.

One of the major goals of our laboratory is to define intracellular events that contribute to antigen presentation by both class I and class II molecules of the major histocompatibility complex (MHC). Initially these studies focused on mapping intracellular transport pathways for both these molecules and establishing what aspects of their transport are critical for antigen presentation, under normal circumstances. More recently our laboratory has been focusing on how pathogens affect these processes. In particular, we are studying viral proteins that interfere with class I molecule assembly and binding of antigenic peptides in the endoplasmic reticulum. In addition, we are analyzing the effects on class II MHC molecule function of bacteria that live in the endocytic pathway and a genetic disease that alters lysosome morphology. All of these systems promise to reveal subtleties of the antigen presentation pathways that have been exploited by pathogens or altered by disease, but have yet to be understood by investigators. Our laboratory is also analyzing the role of clathrin-coated vesicles in sorting class II MHC molecules to the endocytic pathways. This work interfaces with the other major project in the lab that focuses on clathrin structure and function. Recent investigations along these lines have probed the function of the HIV-1 nef protein which affects endocytosis of CD4 and class I MHC molecules and focus on the role of clathrin in Toxoplasma gondii, a micro-organism that causes opportunistic infections in AIDS patients.