HIV-1 replication is dependent on the cellular machinery to produce progeny virus. Given the dependence of the virus on host cell, the recognition step between HIV proteins and cellular factors provides an excellent opportunity for structure-based drug design. My research group focuses on structural studies of protein-protein and protein-membrane interactions associated with HIV. A major effort in my laboratory is to understand the molecular determinants of HIV-host interactions and develop new therapeutic strategies to neutralize the virus.
HIV-1 Gag interactions with cellular constituents. A major hallmark in the late phase of HIV-1 infection is targeting of the Gag polyprotein to the plasma membrane (PM) for assembly. Several cellular proteins have been implicated in HIV-1 Gag trafficking and/or assembly. My lab investigates at the atomic level how the Gag protein interacts with cellular proteins and lipids.
Structural basis for HIV-1 Tat secretion. Successful gene transcription and production of HIV-1 RNA scripts are critically dependent on the trans activator of transcription (Tat) protein. Extracellular Tat has been implicated in deregulation of cytokine secretion by monocytes and lymphocytes, and also in the lethal induction of lymphocyte and neuron death. Tat is unconventionally secreted from the PM through specific interactions with phosphatidylinositiol-4,5-bisphosphate. Studies in my lab are aimed at elucidating the structural basis for Tat-membrane interactions.
HIV drug development. We utilize a structure-based drug design approach to identify HIV inhibitors. We have recently identified a class of anti HIV drugs that are capable of disrupting HIV-host interactions and greatly inhibit HIV production with no detectable toxicity.
Structural basis for Fas-mediated apoptosis. We are interested in understanding how Fas, a protein that is important in cell signaling pathway and is implicated in apoptosis, interacts with the cellular protein calmodulin. Enhanced or diminished apoptosis is associated with many human diseases including neurodegenerative and autoimmune disorders, AIDS, and cancers.