Our lab studies cytotoxic T lymphocytes (CTL) that are key cells in the immune defense against viral infection and cancer. When CTL recognize an infected or transformed cell, they release the contents of their cytolytic granules into the synaptic cleft formed with the target cell. These granules contain serine proteases called granzymes, which induce programmed cell death or apoptosis. A major focus of the lab is studying the molecular pathways activated by the granzymes. Granzyme A, the most abundant CTL protease, induces a novel form of apoptosis that is independent of the caspase pathway and results in single strand nicks of DNA. We have identified novel mechanisms of mitochondrial and DNA damage activated by granzyme A. Other work aims to understand how cytotoxic T lymphocyte function is regulated, particularly in the setting of chronic infections, such as HIV-1.The laboratory also studies how RNA interference (RNAi) regulates normal cell differentiation and how it goes awry in cancer. A major focus is figuring out how RNAi can be harnessed to develop drugs to treat or prevent viral infection and cancer. We showed that RNAi could be the basis for therapy in an animal model. We were able to use small RNAs to inhibit sexual transmission of herpes virus in mice and are working to develop an RNAi-based topical microbicide to prevent HIV transmission. Another active area of research is developing ways of targetting small RNAs into specific cell types in vivo.