My laboratory employs approaches rooted in synthetic immunology as a means of engineering or enhancing the natural immune system with the goal of understanding, preventing and treating HIV infection. We are currently applying these approaches to a number of questions relating to interactions between the virus and the host immune response.

One of the primary interests of the lab is to understand the fundamental mechanisms of HIV neutralization in vivo and the parameters that determine whether a given infection will be established or be cleared by the immune response. While it is clear that HIV infection is typically the result of a small number of viruses establishing infection in the host, the earliest events that dictate this outcome are uncertain. To this end, we are investigating the contribution of innate immunity during the process of antibody-mediated prophylaxis, which may contribute to viral control by targeting infected cells for destruction by innate immune cells.

A second major interest of the lab is to understand the basic evolutionary principles at work during HIV escape from immunological selective pressure. The imperfect nature of HIV replication results in tremendous viral diversity, which enables the rapid outgrowth of resistant genotypes in response to inhibition by either drugs or the immune system. We are engineering sub-therapeutic immunological selective pressure to HIV in vivo as a means of intentionally inducing viral escape, allowing us to observe this process in real-time via deep sequencing. Our hope is that through these efforts, we will improve our understanding of the evolutionary mechanisms employed by HIV and identify weaknesses in the process of viral escape that may enable new treatments capable of suppressing virus while preventing escape.

Finally, the lab continues to be involved in the development of novel concepts in gene transfer with the ultimate goal of translating this technology to the clinic. We are investigating novel vectors for gene transfer to improve the efficiency, specificity and safety of this process. These efforts aim to create new tools for immunological engineering that can be applied to both our basic understanding of host-pathogen interactions as well as contribute to future clinical interventions.