Our laboratory focuses on entry processes of enveloped viruses and the various ways that the innate and adaptive immune responses inhibit these processes. We also apply our insights toward developing therapeutic strategies that enhance or supplement these immune responses. Our work can be divided into three categories: (1) biochemical studies of the HIV-1 entry process and its inhibition, (2) identification and characterization of obligate factors, including receptors, necessary for the entry of other enveloped viruses, and (3) identification and characterization of host restriction factors that inhibit early steps in the viral life cycle, in particular those of the IFITM family.

In addition to these scientific goals, we are developing a means of providing sustained, universal protection from HIV-1. Our most effective strategy uses adeno-associated virus (AAV) to express, eCD4-Ig, an exceptionally broad and potent HIV-1 entry inhibitor. We have shown that this strategy protects rhesus macaques from virus challenges greater than any human is likely to encounter, and thus it provides more effective protection than any conventional vaccine approach. To improve the safety of this approach, we are also developing regulatory switches that can dose or inactivate an AAV transgene.