Our research centers on elucidating molecular mechanisms of HIV (human immunodeficiency virus) viral entry -- that is, how HIV enters host cells and how the viral envelope protein interacts with host cellular receptors. Insights gained from these studies will lead to a much deeper understanding of the mechanisms of viral entry and antibody neutralization, and will also guide development of vaccines and therapeutics. In particular, we focus on the following areas of investigation:

1) Structural studies of HIV envelope glycoprotein in distinct conformational states. We have produced stable and homogeneous preparations of trimeric HIV-1 envelope protein representing each of its principal conformational states: the prefusion conformation, the prehairpin intermediate, and the postfusion conformation. Using these well-defined protein preparations, we and our collaborators are pursuing structural studies by x-ray crystallography, NMR and cryo-electron microscopy. The goal is to generate a molecular "movie" by obtaining structural information for each of these distinct conformational states of HIV envelope protein and to show the complete fusion process.

2) Coreceptor CCR5 and reconstitution of the membrane fusion reaction in vitro. We use biochemical and structural approaches to elucidate the molecular details of the interaction between HIV envelope glycoprotein and the host coreceptor CCR5, and will recapitulate the membrane fusion in vitro, using purified viral and host components.

3) Antibody neutralization mechanism and immunogen design. We study molecular mechanisms of neutralization by broadly neutralizing antibodies against HIV infection. We will design trial immunogens for inducing effective antibody responses, based on knowledge from our biochemical and structural studies.