My interests are in the pathogenic processes of HIV-1 infection. My laboratory concentrates on developing model systems which are more relevant to the pathogenic process in man than are standard in vitro culture approaches, with the eventual goal of using these systems to develop therapeutic strategies for AIDS. We are currently concentrating on three major areas of investigation, which include: 1) use of the SCID-hu mouse as an in vivo model for HIV-1-induced pathogenesis and therapeutic approaches. Studies currently ongoing involve factors involved in immune reconstitution following pharmacologic therapy and novel therapeutic approaches including gene therapy; 2) development of novel in vitro culture systems which mimic the in vivo situation; 3) molecular analysis of reverse transcription defects in non-dividing lymphocytes. We will continue to develop new model systems and explore existing models to answer important questions regarding the mechanisms associated with HIV disease progression. The members of my laboratory feel that increasing the basic knowledge base regarding pathogenesis will allow a more rational approach to the development of therapeutics to either cure or greatly reduce the morbidity associated with this disease.

Recent Publications

Koka PS, Fraser JK, Bryson Y, Bristol GC, Aldrovandi GM, Daar ES, Zack JA (1998) Human immunodeficiency virus inhibits multilineage hematopoiesis in vivo. J. Virol 72: 5121-5127.

Korin YD, Zack JA (1998) Progression to the G1b phase of the cell cycle is required for completion of human immunodeficiency virus type 1 reverse transcription in T cells. J. Virol 72: 3161-3168.

Kitchen SG, Zack JA (1997) CXCR4 expression during lymphopoiesis: omplications for human immunodeficiency virus type 1 infection of the thymus. J. Virol 71: 6928-6934.

Withers-Ward ES, Amado RG, Koka PS, Jamieson BD, Kaplan AH, Chen ISY, Zack JA (1997) Transient renewal of thymopoiesis in HIV-infected human thymic implants following antiviral therapy. Nature Medicine 3: 1102-1109.

Kitchen SG, Uittenbogaart CH, Zack JA (1997) Mechanism of HIV-1 localization in CD4-negative thymocytes: Differentiation from a CD4-positive precursor allows productive infection. J Virol 71: 5713-5722.

Akkina RK, Rosenblatt JD, Campbell AG, Chen ISY, Zack JA (1994) Modeling human stem cell gene therapy in the SCID-hu mouse. Blood 84: 1393-1398.

Aldrovandi GM, Feuer G, Gao L, Jamieson B, Kristeva M, Chen ISY, Zack JA (1993) The SCID-hu mouse as a model for HIV-1 infection. Nature 363: 732-736.