Fields: Immunology and Virology
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Biology 341: Virology
Biology 114: Principles of Biology: The HIV Pandemic
Biology 392: Immunology with lab
Currently, my research focuses on the interplay between a human protein, APOBEC3G, and the HIV (human immunodeficiency virus) viral protein, Vif. I recently identified APOBEC3G as a cellular protein that is highly expressed in T lymphocytes and has potent anti-HIV activity. The possibility of manipulating the APOBEC3G protein as a point of therapeutic intervention is a novel and exciting line of investigation. However, we must first understand both the interaction between Vif and APOBEC3G, and how the cell regulates the expression and function of APOBEC3G. The projects in my lab will be geared toward understanding the regulation of APOBEC3G and whether ultimately manipulating this regulation can significantly enhance and strengthen APOBEC3G anti-viral activity.
Initially, I would like to identify the promoter and putative enhancer regions of the APOBEC3G gene. The successful identification of these regions will lend valuable insight into the specific regulation of this cellular gene that is capable of suppressing HIV infection. Once regions of regulation have been identified, the specifics of how the cell controls this gene expression can be dissected. For example, successful identification of a promoter will delineate which cellular proteins are responsible for controlling APOBEC3G expression. In turn, this determination will allow us to investigate whether we can artificially regulate and manipulate the anti-viral activity of APOBEC3G. And, most importantly, if we can manipulate APOBEC3G, we may be able to boost the cell's ability to defend itself against HIV invasion.
Farrow, M. A. & Sheehy, Ann M. 2008. Vif and Apobec3G in the innate immune response to HIV: a tale of two proteins. Future Microbiol. 3:145-154. (PDF)
Sheehy, Ann M. 2008. Genes and screens: the search for novel chemotherapeutic targets. Future HIV Ther. 2:259-261. pdf
Newman, Edmund N.C., Holmes, Rebecca K., Craig, Heather M., Klein, Kevin C., Lingappa, Jaisiri R., Malim, Michael H., and Sheehy, Ann M. (2005). Anti-Viral Function of APOBEC3G can be Dissociated from Cytidine Deaminase Activity. Curr. Biol.15: 166-70.
Gaddis, Nathan C., Sheehy, Ann M., Ahmad, K. Muneer, Swanson, Chad M., Bishop, Kate N., Beer, Brigitte E., Marx, Preston A., Gao, Feng, Bibollet-Ruche, Frederic, Hahn, Beatrice H., and Malim, Michael H. (2004). Further Investigation of Simian Immunodeficiency Virus Vif Function in Human Cells. J. Virol. 78: 12041-12046.
Bishop, Kate N., Holmes, Rebecca K., Sheehy, Ann M., Davidson, Nicholas O., Cho, Soo-Jin, and Malim, Michael H. (2004). Cytidine Deamination of Retroviral DNA by Diverse APOBEC Proteins. Curr. Biol. 14: 1392-96.
Sheehy, Ann M., Gaddis, Nathan C., and Malim, Michael H. (2003). The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nat. Med. 9: 1404-7.
Harris RS, Sheehy AM, Craig HM, Malim MH, Neuberger MS. (2003). DNA deamination: not just a trigger for antibody diversification but also a mechanism for defense against retroviruses. Nat. Immunol. 4: 641-3.
Harris RS, Bishop KN, Sheehy AM, Craig HM, Petersen-Mahrt SK, Watt IN, Neuberger MS, Malim M.H. (2003). DNA deamination mediates innate immunity to retroviral infection. Cell113: 803-9.
Gaddis, N.C., Chertova, E., Sheehy, A.M., Henderson, L.E. and Malim, M.H. (2003) Comprehensive Investigation of the Molecular Defect in vif-Deficient Human Immunodeficiency Virus Type 1 Virions. J. Virol. 77: 5810-5820.
Sheehy, Ann M., Gaddis, Nathan C., Choi, Jonathan D. and Malim, Michael H. (2002). Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature418: 646-650.
Sheehy, Ann M. and Mark S. Schlissel. (1999). Overexpression of RelA causes G1 arrest and apoptosis in a pro-B cell line. JBC274: 8707-8716.
Simon, James, H.M., Sheehy, Ann M., Carpenter, Elise A., Fouchier, Ron A.M., and Michael H. Malim. (1999). Mutational Analysis of the Human Immunodeficiency Virus Type-1 Vif Protein. J. Virol.73(4): 2675-2681.
Sheehy, Ann. (2004). Regulation of APOBEC3G by Vif. 11th Conference on Retroviruses and Opportunistic Infections. San, Francisco, CA. Invited Speaker.
Sheehy, A.M. and Malim, M.H. (2002) The identification of cellular host factors that contribute to the HIV-1 Vif Phenotype. XIV International AIDS Conference. Barcelona, Spain. Invited Speaker.
Sheehy, A.M. and Malim, M.H. (2002) The identification of cellular host factors important for the HIV-1 Vif Phenotype. 9th Conference on Retroviruses and Opportunistic Infections. Seattle, Washington. Oral presentation.
Sheehy, A.M. and Malim, M.H. (2001) The interaction of cellular host factors with HIV Vif. Cold Spring Harbor Retroviruses Meeting. Cold Spring Harbor, NY Oral presentation.