MICaB Graduate Program
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Ashley T. Haase, M.D.
Regents' Professor and Head
Department of Microbiology and Immunology
Columbia College of Physicians and Surgeons, 1965, M.D.
Viral pathogenesis, HIV
My laboratory investigates the pathogenesis, treatment and prevention of lentiviral immunodeficiency infections caused by HIV-1 and its simian relative, SIV, using such technologies as in situ hybridization, in situ tetramer staining and quantitative image analysis to visualize infection and the hosts’ cellular immune response in tissues. Much of our recent work has focused on sexual mucosal transmission and the acute stage of SIV infection, the roles of “resting” and activated CD4 T cells in establishing infection, and the mechanisms of the massive depletion of CD4 T cells in the gut. Going forward, these studies provide a foundation for studies of the correlates of protection for attenuated vaccines, and the development of vaccines and microbicides to prevent transmission. My laboratory has also undertaken a comprehensive microarray analysis of HIV-1 and SIV infections with the objectives of understanding pathogenesis and identifying novel targets for treatment and prevention. Current efforts focus on broadening the microarray analysis to encompass the early through late stages of HIV-1 infection, and mapping genes identified in the analysis to gain insight into their function in HIV-1 infected lymphatic tissues, the principal sites of virus production, persistence and pathology.
Selected Recent Publications:
- Li Q, Smith AJ, Schacker TW, Carlis JV, Duan L, Reilly CS, Haase AT. Microarray analysis of lymphatic tissue reveals stage-specific, gene expression signatures in HIV-1 infection. J Immunol. 2009 Aug 1;183(3):1975-82. Epub 2009 Jul 13.
- Li Q, Estes JD, Schlievert PM, Duan L, Brosnahan AJ, Southern PJ, Reilly CS, Peterson ML, Schultz-Darken N, Brunner KG, Nephew KR, Pambuccian S, Lifson JD, Carlis JV, Haase AT. Glycerol monolaurate prevents mucosal SIV transmission. Nature. 2009 Apr 23;458(7241):1034-8. Epub 2009 Mar 4.
- Li Q, Skinner PJ, Ha SJ, Duan L, Mattila TL, Hage A, White C, Barber DL, O'Mara L, Southern PJ, Reilly CS, Carlis JV, Miller CJ, Ahmed R, Haase AT. Visualizing antigen-specific and infected cells in situ predicts outcomes in early viral infection. Science. 2009 Mar 27;323(5922):1726-9.
- Schacker T.W., Brenchley J.M., Beilman G.J., Reilly C., Pambuccian S.E., Taylor J., Skarda D., Larson M., Douek D.C, Haase A.T. 2006. Lymphatic tissue fibrosis is associated with reduced numbers of naive CD4+ T cells in human immunodeficiency virus type 1 infection. Clin Vaccine Immunol. 13(5):556-60.
- Estes J.D., Li Q., Reynolds M.R., Wietgrefe S., Duan L., Schacker T., Picker L.J., Watkins D.I., Lifson J.D., Reilly C., Carlis J., Haase A.T. 2006. Premature induction of an immunosuppressive regulatory T cell response during acute simian immunodeficiency virus infection. J Infect Dis. 193(5):703-12.
- Schacker TW, Reilly C, Beilman GJ, Taylor J, Skarda D, Krason D, Larson M, Haase AT. 2005. Amount of lymphatic tissue fibrosis in HIV infection predicts magnitude of HAART-associated change in peripheral CD4 cell count. AIDS. 19(18):2169-71.
- Li, Q., T. Schacker, J. Carlis, G. Beilman, P. Nguyen, and A.T. Haase. 2004. Functional genomic analysis of the response of HIV-1 infected lymphatic tissue to antiretroviral therapy. J. Infect. Dis. 189: 572-582.
- Li, Q., L. Duan, J.D. Estes, Z.-M. Ma, T. Rourke, Y. Wang, C. Reilly, J. Carlis, C.J. Miller, and A.T. Haase. 2005. Peak SIV replication in “resting” memory CD4 T cells depletes gut lamina propria CD4 T cells. Nature 434: 1148-1152.
- Haase, A.T. 2005. Perils at mucosal front lines for HIV and SIV and and their hosts. Nature Rev. Immunol. 5: 783-792.