Photo of Dana H. Gabuzda,  MD

Dana H. Gabuzda, MD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute

Dana H. Gabuzda, MD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Professor, Neurology, Harvard Medical School
  • Associate Physician, Neurology, Brigham And Women's Hospital
  • Professor of Neurology (Microbiology), Cancer Immunology and Virology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

The major research interest of the Gabuzda lab is to understand molecular mechanisms of HIV replication and pathogenesis, and their implications for understanding pathogen-host interactions, immune responses, and disease outcomes. Using biological, genetic, biochemical, and systems biology approaches, we study: 1) HIV replication and pathogenesis in the immune system and central nervous system; 2) mechanisms and pathways underlying differences in host responses to viral infection and antiretroviral therapy; 3) viral diversity and tropism for specific cell types and tissues; 4) functions of the HIV Env, Vif, and Nef proteins; 5) high-throughput screening assays to identify small molecules that inhibit Vif interaction with its host cell cofactor APOBEC3G.

 

Publications

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  • Mefford ME, Kunstman K, Wolinsky SM, Gabuzda D. Bioinformatic analysis of neurotropic HIV envelope sequences identifies polymorphisms in the gp120 bridging sheet that increase macrophage-tropism through enhanced interactions with CCR5. Virology 2015; 481:210-22. PubMed
  • Pery E, Sheehy A, Miranda Nebane N, Misra V, Mankowski MK, Rasmussen L, Lucile White E, Ptak RG, Gabuzda D. Redoxal, an inhibitor of de novo pyrimidine biosynthesis, augments APOBEC3G antiviral activity against human immunodeficiency virus type 1. Virology 2015; 484:276-287. PubMed
  • Cassol E, Misra V, Morgello S, Kirk GD, Mehta SH, Gabuzda D. Altered Monoamine and Acylcarnitine Metabolites in HIV-Positive and HIV-Negative Subjects With Depression. J Acquir Immune Defic Syndr 2015; 69:18-28. PubMed
  • Pery E, Sheehy A, Nebane NM, Brazier AJ, Misra V, Rajendran KS, Buhrlage SJ, Mankowski MK, Rasmussen L, White EL, Ptak RG, Gabuzda D. Identification of a novel HIV-1 inhibitor targeting Vif-dependent degradation of human APOBEC3G protein. J Biol Chem 2015. PubMed
  • Cassol E, Misra V, Dutta A, Morgello S, Gabuzda D. Cerebrospinal fluid metabolomics reveals altered waste clearance and accelerated aging in HIV patients with neurocognitive impairment. AIDS 2014. PubMed
  • Yen PJ, Mefford ME, Hoxie JA, Williams KC, Desrosiers RC, Gabuzda D. Identification and characterization of a macrophage-tropic SIV envelope glycoprotein variant in blood from early infection in SIVmac251-infected macaques. Virology 2014; 458-459:53-68. PubMed
  • Yen PJ, Herschhorn A, Haim H, Salas I, Gu C, Sodroski J, Gabuzda D. Loss of a conserved N-linked glycosylation site in the simian immunodeficiency virus envelope glycoprotein V2 region enhances macrophage tropism by increasing CD4-independent cell-to-cell transmission. J Virol 2014; 88:5014-28. PubMed
  • Cassol E, Misra V, Morgello S, Gabuzda D. Applications and limitations of inflammatory biomarkers for studies on neurocognitive impairment in HIV infection. 2013; 8:1087-97. PubMed
  • Gabuzda D, Yankner BA. Physiology: Inflammation links ageing to the brain. Nature 2013; 497:197-8. PubMed
  • Cassol E, Cassetta L, Rizzi C, Gabuzda D, Alfano M, Poli G. Dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin mediates HIV-1 infection of and transmission by M2a-polarized macrophages in vitro. AIDS 2013. PubMed
  • Cassol E, Misra V, Holman A, Kamat A, Morgello S, Gabuzda D. Plasma metabolomics identifies lipid abnormalities linked to markers of inflammation, microbial translocation, and hepatic function in HIV patients receiving protease inhibitors. BMC Infect Dis 2013; 13:203. PubMed
  • Yan Z, Shah PK, Amin SB, Samur MK, Huang N, Wang X, Misra V, Ji H, Gabuzda D, Li C. Integrative analysis of gene and miRNA expression profiles with transcription factor-miRNA feed-forward loops identifies regulators in human cancers. Nucleic Acids Res 2012; 40:e135. PubMed
  • Kamat A, Lyons JL, Misra V, Uno H, Morgello S, Singer EJ, Gabuzda D. Monocyte activation markers in cerebrospinal fluid associated with impaired neurocognitive testing in advanced HIV infection. J Acquir Immune Defic Syndr 2012; 60:234-43. PubMed
  • Holman AG, Gabuzda D. A machine learning approach for identifying amino acid signatures in the HIV env gene predictive of dementia. PLoS ONE 2012; 7:e49538. PubMed
  • Mukerji J, Olivieri KC, Misra V, Agopian KA, Gabuzda D. Proteomic analysis of HIV-1 Nef cellular binding partners reveals a role for exocyst complex proteins in mediating enhancement of intercellular nanotube formation. Retrovirology 2012; 9:33. PubMed
  • Lyons JL, Uno H, Ancuta P, Kamat A, Moore DJ, Singer EJ, Morgello S, Gabuzda D. Plasma sCD14 is a biomarker associated with impaired neurocognitive test performance in attention and learning domains in HIV infection. J Acquir Immune Defic Syndr 2011; 57:371-9. PubMed
  • Gray LR, Gabuzda D, Cowley D, Ellett A, Chiavaroli L, Wesselingh SL, Churchill MJ, Gorry PR. CD4 and MHC class 1 down-modulation activities of nef alleles from brain- and lymphoid tissue-derived primary HIV-1 isolates. J Neurovirol 2011; 17:82-91. PubMed
  • Holman AG, Mefford ME, O'Connor N, Gabuzda D. HIVBrainSeqDB: a database of annotated HIV envelope sequences from brain and other anatomical sites. AIDS Res Ther 2011; 7:43. PubMed
  • Kamat A, Ancuta P, Blumberg RS, Gabuzda D. Serological markers for inflammatory bowel disease in AIDS patients with evidence of microbial translocation. PLoS ONE 2010; 5:e15533. PubMed
  • Gray L, Roche M, Churchill MJ, Sterjovski J, Ellett A, Poumbourios P, Sherieff S, Sheffief S, Wang B, Saksena N, Purcell DF, Wesselingh S, Cunningham AL, Brew BJ, Gabuzda D, Gorry PR. Tissue-specific sequence alterations in the human immunodeficiency virus type 1 envelope favoring CCR5 usage contribute to persistence of dual-tropic virus in the brain. J Virol 2009; 83:5430-41. PubMed
  • Haim H, Si Z, Madani N, Wang L, Courter JR, Princiotto A, Kassa A, DeGrace M, McGee-Estrada K, Mefford M, Gabuzda D, Smith AB, Sodroski J. Soluble CD4 and CD4-mimetic compounds inhibit HIV-1 infection by induction of a short-lived activated state. PLoS Pathog. 2009; 5:e1000360. PubMed
  • Pery E, Rajendran KS, Brazier AJ, Gabuzda D. Regulation of APOBEC3 proteins by a novel YXXL motif in human immunodeficiency virus type 1 Vif and simian immunodeficiency virus SIVagm Vif. J Virol 2009; 83:2374-81. PubMed
  • Ancuta P, Liu KY, Misra V, Wacleche VS, Gosselin A, Zhou X, Gabuzda D. Transcriptional profiling reveals developmental relationship and distinct biological functions of CD16+ and CD16- monocyte subsets. BMC Genomics 2009; 10:403. PubMed
  • Mefford ME, Gorry PR, Kunstman K, Wolinsky SM, Gabuzda D. Bioinformatic prediction programs underestimate the frequency of CXCR4 usage by R5X4 HIV type 1 in brain and other tissues. AIDS Res Hum Retroviruses 2008; 24:1215-20. PubMed
  • Wang J, Shackelford JM, Selliah N, Shivers DK, O'Neill E, Garcia JV, Muthumani K, Weiner D, Yu XF, Gabuzda D, Finkel TH. The HIV-1 Vif Protein Mediates Degradation of Vpr and Reduces Vpr-Induced Cell Cycle Arrest. DNA Cell Biol 2008; 27:267-77. PubMed
  • Ancuta P, Kamat A, Kunstman KJ, Kim EY, Autissier P, Wurcel A, Zaman T, Stone D, Mefford M, Morgello S, Singer EJ, Wolinsky SM, Gabuzda D. Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients. PLoS ONE 2008; 3:e2516. PubMed
  • Loerch PM,Lu T,Dakin KA,Vann JM,Isaacs A,Geula C,Wang J,Pan Y,Gabuzda DH,Li C,Prolla TA,Yankner BA. Evolution of the aging brain transcriptome and synaptic regulation. PLoS ONE 2008; 3:e3329. PubMed
  • Mehle A, Wilson H, Zhang C, Brazier AJ, McPike M, Pery E, Gabuzda D. Identification of an APOBEC3G binding site in human immunodeficiency virus type 1 Vif and inhibitors of Vif-APOBEC3G binding. J Virol 2007; 81:13235-41. PubMed
  • Dunfee RL, Thomas ER, Wang J, Kunstman K, Wolinsky SM, Gabuzda D. Loss of the N-linked glycosylation site at position 386 in the HIV envelope V4 region enhances macrophage tropism and is associated with dementia. Virology 2007; 367:222-34. PubMed
  • Verity EE, Zotos D, Wilson K, Chatfield C, Lawson VA, Dwyer DE, Cunningham A, Learmont J, Dyer W, Sullivan J, Churchill M, Wesselingh SL, Gabuzda D, Gorry PR, McPhee DA. Viral phenotypes and antibody responses in long-term survivors infected with attenuated human immunodeficiency virus type 1 containing deletions in the nef and long terminal repeat regions. J Virol 2007; 81:9268-78. PubMed
  • Gorry PR, Dunfee RL, Mefford ME, Kunstman K, Morgan T, Moore JP, Mascola JR, Agopian K, Holm GH, Mehle A, Taylor J, Farzan M, Wang H, Ellery P, Willey SJ, Clapham PR, Wolinsky SM, Crowe SM, Gabuzda D. Changes in the V3 region of gp120 contribute to unusually broad coreceptor usage of an HIV-1 isolate from a CCR5 Delta32 heterozygote. Virology 2007; 362:163-78. PubMed
  • Thomas ER, Dunfee RL, Stanton J, Bogdan D, Kunstman K, Wolinsky SM, Gabuzda D. High Frequency of Defective vpu Compared with tat and rev Genes in Brain from Patients with HIV Type 1-Associated Dementia. AIDS Res Hum Retroviruses 2007; 23:575-80. PubMed
  • Thomas ER, Dunfee RL, Stanton J, Bogdan D, Taylor J, Kunstman K, Bell JE, Wolinsky SM, Gabuzda D. Macrophage entry mediated by HIV Envs from brain and lymphoid tissues is determined by the capacity to use low CD4 levels and overall efficiency of fusion. Virology 2006; 360:105-19. PubMed
  • Agopian K, Wei BL, Garcia JV, Gabuzda D. CD4 and MHC-I downregulation are conserved in primary HIV-1 Nef alleles from brain and lymphoid tissues, but Pak2 activation is highly variable. Virology 2006; 358:119-35. PubMed
  • Gray L, Churchill MJ, Sterjovski J, Witlox K, Learmont JC, Sullivan JS, Wesselingh SL, Gabuzda D, Cunningham AL, McPhee DA, Gorry PR. Phenotype and envelope gene diversity of nef-deleted HIV-1 isolated from long-term survivors infected from a single source. Virol J 2007; 4:75. PubMed
  • Gorry PR, McPhee DA, Verity E, Dyer WB, Wesselingh SL, Learmont J, Sullivan JS, Roche M, Zaunders JJ, Gabuzda D, Crowe SM, Mills J, Lewin SR, Brew BJ, Cunningham AL, Churchill MJ. Pathogenicity and immunogenicity of attenuated, nef-deleted HIV-1 strains in vivo. Retrovirology 2007; 4:66. PubMed
  • Sterjovski J, Churchill MJ, Ellett A, Gray LR, Roche MJ, Dunfee RL, Purcell DF, Saksena N, Wang B, Sonza S, Wesselingh SL, Karlsson I, Fenyo EM, Gabuzda D, Cunningham AL, Gorry PR. Asn 362 in gp120 contributes to enhanced fusogenicity by CCR5-restricted HIV-1 envelope glycoprotein variants from patients with AIDS. Retrovirology 2007; 4:89. PubMed
  • Wang J, Gabuzda D. Reconstitution of human immunodeficiency virus-induced neurodegeneration using isolated populations of human neurons, astrocytes, and microglia and neuroprotection mediated by insulin-like growth factors. J Neurovirol 2006; 12:472-91. PubMed
  • Ancuta P, Wang J, Gabuzda D. CD16+ monocytes produce IL-6, CCL2, and matrix metalloproteinase-9 upon interaction with CX3CL1-expressing endothelial cells. J Leukoc Biol 2006; 80:1156-64. PubMed
  • Dunfee RL, Thomas ER, Gorry PR, Wang J, Taylor J, Kunstman K, Wolinsky SM, Gabuzda D. The HIV Env variant N283 enhances macrophage tropism and is associated with brain infection and dementia. Proc Natl Acad Sci U S A 2006; 103:15160-5. PubMed
  • Dunfee R, Thomas ER, Gorry PR, Wang J, Ancuta P, Gabuzda D. Mechanisms of HIV-1 neurotropism. Curr HIV Res 2006; 4:267-78. PubMed
  • Mehle A, Thomas ER, Rajendran KS, Gabuzda D. A zinc-binding region in Vif binds Cul5 and determines cullin selection. J Biol Chem 2006; 281:17259-65. PubMed
  • Ancuta P, Autissier P, Wurcel A, Zaman T, Stone D, Gabuzda D. CD16+ monocyte-derived macrophages activate resting T cells for HIV infection by producing CCR3 and CCR4 ligands. J Immunol 2006; 176:5760-71. PubMed
  • Reche PA, Keskin DB, Hussey RE, Ancuta P, Gabduza D, Reinherz EL. Elicitation from virus-naive individuals of cytotoxic T lymphocytes directed against conserved HIV-1 epitopes. Med Immunol 2006; 5:1. PubMed
  • Gray L, Churchill MJ, Keane N, Sterjovski J, Ellett AM, Purcell DF, Poumbourios P, Kol C, Wang B, Saksena NK, Wesselingh SL, Price P, French M, Gabuzda D, Gorry PR. Genetic and functional analysis of R5X4 human immunodeficiency virus type 1 envelope glycoproteins derived from two individuals homozygous for the CCR5delta32 allele. J Virol 2006; 80:3684-91. PubMed
  • Churchill MJ, Gorry PR, Cowley D, Lal L, Sonza S, Purcell DF, Thompson KA, Gabuzda D, McArthur JC, Pardo CA, Wesselingh SL. Use of laser capture microdissection to detect integrated HIV-1 DNA in macrophages and astrocytes from autopsy brain tissues. J Neurovirol 2006; 12:146-52. PubMed
  • Agopian K, Wei BL, Garcia JV, Gabuzda D. A hydrophobic binding surface on the human immunodeficiency virus type 1 Nef core is critical for association with p21-activated kinase 2. J Virol 2006; 80:3050-61. PubMed
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