• Researcher Profile

    Dana H. Gabuzda, MD

    Dana H. Gabuzda, MD
    Professor of Neurology, Harvard Medical School

    Office phone: 617-632-2154
    Fax: 617-632-4338
    Email: dana_gabuzda@dfci.harvard.edu

    Preferred contact method: office phone

    Research Department

    Cancer Immunology and Virology

    Area of Research

    Mechanisms of HIV Replication and Pathogenesis

    Dana-Farber Cancer Institute
    450 Brookline Avenue
    CLS 1010
    Boston, MA 02215


    Dr. Gabuzda received her MD from Harvard Medical School in 1983 and did her postgraduate training in internal medicine and neurology at Massachusetts General Hospital. After completing research fellowships at Johns Hopkins University and DFCI, she joined the DFCI faculty in 1991. She is primarily involved in basic laboratory research on HIV replication and disease mechanisms in AIDS.


    Mechanisms of HIV Replication and Pathogenesis

    The major research interest of our lab is to understand the mechanisms of HIV replication and disease pathogenesis. One focus of this research is on HIV pathogenesis in the immune system and central nervous system (CNS). For this work, we developed in vitro model systems to study HIV entry, replication, persistence, and cell death in immune-system and CNS cells. We identified chemokine receptors that mediate viral entry in the CNS, and are now studying envelope-receptor interactions that influence viral tropism and pathogenicity. We are also investigating how HIV infection causes neuronal apoptosis and CNS injury, focusing on mechanisms of cytopathicity induced by the HIV envelope glycoproteins and the role of the viral Nef protein in the activation of cell signaling pathways. In other efforts, we are studying the mechanisms that lead to apoptosis of T cells during HIV infection, and investigating the CD16+ proinflammatory monocyte subset and its role in the pathogenesis of HIV/AIDS.

    A second major research interest of our laboratory is to understand the mechanism by which the HIV Vif (viral infectivity factor) protein overcomes the innate antiviral activity of APOBEC3G, a cellular cytidine deaminase that induces G to A hypermutation in newly synthesized viral DNA. In the absence of Vif, APOBEC3G incorporation into virions renders HIV noninfectious. We demonstrated that Vif overcomes the antiviral activity of APOBEC3G by targeting it for destruction by the ubiquitin-proteasome pathway. Vif binds directly to APOBEC3G and forms a complex with Cullin 5, elongin B, and elongin C, suggesting that Vif induces APOBEC3G degradation through a Cullin 5 E3 ubiquitin ligase complex. Current efforts are focused on understanding the mechanisms by which Vif induces degradation of APOBEC3G through association with a Cullin 5 complex. We are also developing high-throughput assays to identify small molecules that inhibit Vif-APOBEC3G interactions. These studies will provide a better understanding of virus-host cell interactions in HIV replication, and will also advance the development of Vif as a target for antiviral therapy.

    Select Publications

    • Ancuta P, Rao R, Moses A, Mehle A, Shaw SK, Luscinskas FW, Gabuzda D. Fractalkine preferentially mediates arrest and migration of CD16+ monocytes. J Exp Med 2003;197:1701-7.
    • Öhagen A, Devitt A, Kunstman K, Gorry PR, Rose PP, Korber B, Taylor J, Levy R, Murphy RL, Wolinsky SM, Gabuzda D. Genetic and functional analysis of full-length HIV-1 env genes derived from brain and blood of AIDS patients. J Virol 2003;77:12336-45.
    • Mehle A, Strack B, Ancuta P, Zhang C, McPike M, Gabuzda D. Vif overcomes the innate antiviral activity of APOBEC3G by promoting its degradation in the ubiquitin-proteasome pathway. J Biol Chem 2004;279:7792-8.
    • Holm GH, Zhang C, Gorry PR, Peden K, Schols D, De Clercq E, Gabuzda D. Apoptosis of bystander T cells induced by human immunodeficiency virus type 1 with increased envelope/receptor affinity and coreceptor binding site exposure. J Virol 2004;78:4541-51.
    • Wang J, Babcock GJ, Choe H, Farzan M, Sodroski J, Gabuzda D. N-linked glycosylation in the CXCR4 N-terminus inhibits binding to the HIV-1 envelope glycoproteins. Virology 2004;324:140-50.
    • Ancuta P, Moses A, Gabuzda D. Transendothelial migration of CD16+ monocytes in response to fractalkine under constitutive and inflammatory conditions. Immunobiology 2004;209:11-20.
    • Mehle A, Goncalves J, Santa-Marta M, McPike M, Gabuzda D. Phosphorylation of a novel SOCS-box regulates assembly of the HIV-1 Vif-Cul5 complex that promotes APOBEC3G degradation. Genes Dev 2004;18:2861-6.
    • Holm G, Gabuzda D. Distinct mechanisms of CD4+ and CD8+ T cell activation and bystander apoptosis induced by human immunodeficiency virus type 1 virions. J Virol 2005;75:6299-311.
    • Gorry PR, Churchill M, Crowe SM, Cunningham AL, Gabuzda D. Pathogenesis of macrophage tropic HIV-1. Curr HIV Res 2005;3:53-60.
    • *Ancuta P, Kunstman KJ, Autissier P, Zaman T, Stone D, Wolinsky SM, Gabuzda D. CD16+ monocytes exposed to HIV promote highly efficient viral replication upon differentiation into macrophages and interaction with T cells. Virology 2005 (in press).


    • Ancuta, Petronela, PhD
    • Wang, Jianbin, MD, PhD
    • Rajendran, Raj, Ph.D.
    • Thomas, Elaine, Ph.D.
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