Mammalian cells resist viruses through a collection of mechanisms termed innate or intrinsic immunity.  These mechanisms differ from the classical adaptive immune response in which B, T helper and cytolytic T cells recognize foreign antigens and clonally expand upon engagement of their antigen receptor.  Intrinsic and innate mechanisms are more general. They are active in many different cell types; some are constitutively active and others are induced by type-I interferons. Some innate immune mechanisms are activated by toll-like receptors or related proteins that warn the cell of the presence of a foreign invader by sensing the viral RNA or DNA in the cytoplasm of the cell. Over the course of evolution, viruses have responded by developing remarkable and diverse ways to escape the adaptive and innate responses.  A focus of our research is to understand how innate immune mechanisms restrict retroviruses and how the viruses counteract them.  We have contributed to understanding how two of these factors, APOBEC3 and SAMHD1, restrict HIV and how they are counteracted by the viral accessory proteins Vpx, Vpr and Vif. We are interested to identify new host restriction factors and to understand how cells sense the presence of invading pathogens.  Ultimately, we are interested to use our understanding to devise new therapeutic strategies that will mobilize the immune system to target pathogens. We are currently extending our interests to using this knowledge to mobilize the immune system to fight cancer.