Dana Gabuzda, M.D.
Associate Head, Virology Program
Professor of Neurology
Dana Farber Cancer Institute
44 Binney St. JF 816
Boston, MA 02115
Tel: 617-632-2154
Fax: 617-632-3113
e-mail:dana_gabuzda@dfci.harvard.edu
4 postdoctoral fellows, 3 graduate students
We study HIV replication, pathogenesis, and virus-host interactions using molecular, biochemical, and genetic approaches. Current areas of investigation include:
HIV Vif and APOBEC3 proteins. Vif overcomes the innate antiviral activity of APOBEC3G (A3G) and 3F, cytidine deaminases that induce hypermutation in HIV proviral DNA, by forming a Vif-Cul5 E3 ligase that targets these proteins for degradation by the ubiquitin-proteasome pathway and by other mechanisms that are not yet defined. We are investigating mechanisms of Vif and APOBEC3 protein function, and Vif interactions with A3G and other host cell factors. We are also developing high-throughput screens to identify Vif inhibitors, and characterizing the small molecules identified in these screens.
HIV Nef interactions with cellular proteins and signaling pathways. Nef is a viral accessory protein required for HIV replication in resting T cells and disease pathogenesis. We are investigating Nef interactions with signaling molecules and other host cell proteins, and mechanisms by which these interactions influence T cell activation and viral pathogenesis using proteomics, biochemical, and genetic approaches.
HIV/AIDS pathogenesis. We are studying mechanisms of HIV pathogenesis in the immune system and central nervous system. We seek to define mechanisms that influence HIV tropism for macrophages, an important cellular reservoir for infection and viral persistence in brain and other tissues. We also study mechanisms that drive chronic inflammation and neurodegeneration in HIV/AIDS. Finally, we are investigating links between loss of CD4 T cells, chronic immune activation, other systemic events (including microbial translocation from the gut), and pathogenic processes in brain and other tissues to better understand disease mechanisms.
References:
- 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.
- 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.
- Mehle A, Thomas ER, Rajendran KS, Gabuzda D. A zinc-binding region in Vif binds Cul5 and determines cullin selection. J Biol Chem 2006;281:17259.
- Dunfee, RL, Thomas ER, Gorry PR, Wang J, Taylor J, Kunstman K, Wolinsky SM, and Gabuzda, D. The HIV Env variant N283 enhances macrophage tropism and is associated with brain infection and dementia. Proc Natl Acad Sci USA 2006;103:15160-65.
- Agopian K, Wei BL, Garcia JV, and Gabuzda D. A hydrophobic binding surface on the HIV-1 1 Nef core is critical for association with p21-activate kinase 2. J Virol 2006;80:3050.
- Mehle A, Wilson H, Zhang C, Brazier AJ, McPike M, Pery E and Gabuzda D. Identification of an APOBEC3G binding site in HIV-1 Vif and inhibitors of Vif-APOBEC3G binding. J. Virol. 2007;81:13235.
- Ancuta P, Kamat A, Kunstman KJ E, Autissier P, Wurcel A, Zaman T, Stone D, Mefford M, Morgello S, Singer EJ, Wolinsky SM, and Gabuzda D. Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients. PloS ONE 2008;3:2516.
Immunology webpage updated 12/02/2009