Research Interests

I direct a research program that aims to understand the host responses that underlie the persistent seronegativity of certain individuals despite high level HIV exposure and the slow disease progression observed in a subset of HIV infected persons. The carriage of certain gene combinations encoding NK cell receptor (NKR) HLA ligand pairs have been shown to be associated with these 2 HIV related outcomes. Currently, my approach is to investigate the responses of NK cells to autologous HIV infected CD4+ T cells from individuals typed for KIR region genes and major histocompatibility complex class I (MHC-I) genes. Using this experimental system, I examine the role of NK cell education and the effect of HIV on cell surface NKR ligand expression on NK cell responses at the NK cell population levels. Another approach to investigating the role of NK cells in HIV outcomes is to assess the ability of anti-HIV gp120 specific antibodies from HIV infected individuals with defined HIV outcomes (Elite Controllers, Viral Controllers, typical progressors, successfully treated HIV positive individuals and persons at defined times in primary HIV infection) to support antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent complement deposition (ADCP, antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular trogocytosis (ADCT) and antibody-dependent NK cell activation (ADNKA). Patterns of these antibody dependent functions will be investigated for their ability to control the size of HIV reservoirs, their evolution during early HIV infection and their fate following initiation of antiretroviral therapy at defined times post infection.