Photo of Joseph G. Sodroski,  MD

Joseph G. Sodroski, MD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-3371
Fax: (617) 632-4338


joseph_sodroski@dfci.harvard.edu

Joseph G. Sodroski, MD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Professor, Immunology and Infectious Diseases, Harvard T.H. Chan School Of Public Health
  • Professor, Microbiology and Immunobiology, Harvard Medical School
  • Associate Director, Harvard Medical School Center for AIDS Research, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

Major interests of the laboratory are human immunodeficiency virus entry and pathogenesis. Central to both of these processes are the viral envelope glycoproteins, which mediate the binding and fusion of the virus with the target cell and the cytopathic effects of infection. The laboratory is devoted to understanding how virus entry occurs at the molecular level and how neutralizing antibodies interfere with virus entry. Means of eliciting neutralizing antibodies with broader reactivity are being explored. The mechanisms of viral cytopathic effects and the contribution of these processes to CD4 lymphocyte depletion in vivo are being studied.

Another interest of the laboratory is the species-specific block to HIV-1 that operates after virus entry. A component of cytoplasmic bodies, TRIM5α, blocks HIV-1 in Old World monkey cells. Human TRIM5α also exhibits anti-HIV-1 activity, but this is less potent than the monkey orthologue. The mechanism of action and the role of species-specific and individual variation in TRIM5α in virus resistance are being explored.

Publications from Harvard Catalyst Profiles

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  • Tipper C, Sodroski JG. Contribution of glutamine residues in the helix 4-5 loop to capsid-capsid interactions in simian immunodeficiency virus of macaques. J Virol 2014; 88:10289-302. PubMed
  • Li X, Kim J, Song B, Finzi A, Pacheco B, Sodroski J. Virus-specific effects of TRIM5α(rh) RING domain functions on restriction of retroviruses. J Virol 2013. PubMed
  • Bird GH, Madani N, Perry AF, Princiotto AM, Supko JG, He X, Gavathiotis E, Sodroski JG, Walensky LD. Hydrocarbon double-stapling remedies the proteolytic instability of a lengthy peptide therapeutic. Proc Natl Acad Sci U S A 2010; 107:14093-8. PubMed
  • Reszka N, Zhou C, Song B, Sodroski JG, Knipe DM. Simian TRIM5alpha proteins reduce replication of herpes simplex virus. Virology 2010; 398:243-50. PubMed
  • Gopi H, Umashankara M, Pirrone V, Lalonde J, Madani N, Tuzer F, Baxter S, Zentner I, Cocklin S, Jawanda N, Miller SR, Schon A, Klein JC, Freire E, Krebs FC, Smith AB, Sodroski J, Chaiken I. Structural Determinants for Affinity Enhancement of a Dual Antagonist Peptide Entry Inhibitor of Human Immunodeficiency Virus Type-1. J Med Chem 2008; 51:2638-2647. PubMed
  • Karlsson Hedestam GB, Fouchier RA, Phogat S, Burton DR, Sodroski J, Wyatt RT. The challenges of eliciting neutralizing antibodies to HIV-1 and to influenza virus. Nat Rev Microbiol 2008; 6:143-55. PubMed
  • Pacheco B, Basmaciogullari S, Labonte JA, Xiang SH, Sodroski J. Adaptation of the human immunodeficiency virus type 1 envelope glycoproteins to new world monkey receptors. J Virol 2008; 82:346-57. PubMed
  • Mendu DR, Katinger H, Sodroski J, Kim KS. HIV-1 envelope protein gp140 binding studies to human brain microvascular endothelial cells. Biochem Biophys Res Commun 2007; 363:466-71. PubMed
  • Javanbakht H, Diaz-Griffero F, Yuan W, Yeung DF, Li X, Song B, Sodroski J. The ability of multimerized cyclophilin A to restrict retrovirus infection. Virology 2007; 367:19-29. PubMed
  • Liu D, Madani N, Li Y, Cao R, Choi WT, Kawatkar SP, Lim MY, Kumar S, Dong CZ, Wang J, Russell JD, Lefebure CR, An J, Wilson S, Gao YG, Pallansch LA, Sodroski JG, Huang Z. Crystal structure and structural mechanism of a novel anti-human immunodeficiency virus and D-amino acid-containing chemokine. J Virol 2007; 81:11489-98. PubMed
  • Diaz-Griffero F, Kar A, Perron M, Xiang SH, Javanbakht H, Li X, Sodroski J. Modulation of retroviral restriction and proteasome inhibitor-resistant turnover by changes in the TRIM5alpha B-box 2 domain. J Virol 2007; 81:10362-78. PubMed
  • Li X, Song B, Xiang SH, Sodroski J. Functional interplay between the B-box 2 and the B30.2(SPRY) domains of TRIM5alpha. Virology 2007; 366:234-44. PubMed
  • Huang CC, Lam SN, Acharya P, Tang M, Xiang SH, Hussan SS, Stanfield RL, Robinson J, Sodroski J, Wilson IA, Wyatt R, Bewley CA, Kwong PD. Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4. Science 2007; 317:1930-4. PubMed
  • Yang X, Lipchina I, Lifton M, Wang L, Sodroski J. Antibody binding in proximity to the receptor/glycoprotein complex leads to a basal level of virus neutralization. J Virol 2007; 81:8809-13. PubMed
  • Ulm JW, Perron M, Sodroski J, C Mulligan R. Complex determinants within the Moloney murine leukemia virus capsid modulate susceptibility of the virus to Fv1 and Ref1-mediated restriction. Virology 2007; 363:245-55. PubMed
  • Dey B, Pancera M, Svehla K, Shu Y, Xiang SH, Vainshtein J, Li Y, Sodroski J, Kwong PD, Mascola JR, Wyatt R. Characterization of human immunodeficiency virus type 1 monomeric and trimeric gp120 glycoproteins stabilized in the CD4-bound state: antigenicity, biophysics, and immunogenicity. J Virol 2007; 81:5579-93. PubMed
  • Basmaciogullari S, Pacheco B, Bour S, Sodroski J. Specific interaction of CXCR4 with CD4 and CD8alpha: Functional analysis of the CD4/CXCR4 interaction in the context of HIV-1 envelope glycoprotein-mediated membrane fusion. Virology 2006; 353:52-67. PubMed
  • Javanbakht H, Yuan W, Yeung DF, Song B, Diaz-Griffero F, Li Y, Li X, Stremlau M, Sodroski J. Characterization of TRIM5alpha trimerization and its contribution to human immunodeficiency virus capsid binding. Virology 2006; 353:234-46. PubMed
  • Diaz-Griffero F, Vandegraaff N, Li Y, McGee-Estrada K, Stremlau M, Welikala S, Si Z, Engelman A, Sodroski J. Requirements for capsid-binding and an effector function in TRIMCyp-mediated restriction of HIV-1. Virology 2006; 351:404-19. PubMed
  • Yuan W, Bazick J, Sodroski J. Characterization of the multiple conformational States of free monomeric and trimeric human immunodeficiency virus envelope glycoproteins after fixation by cross-linker. J Virol 2006; 80:6725-37. PubMed
  • Li X, Li Y, Stremlau M, Yuan W, Song B, Perron M, Sodroski J. Functional replacement of the RING, B-box 2, and coiled-coil domains of tripartite motif 5alpha (TRIM5alpha) by heterologous TRIM domains. J Virol 2006; 80:6198-206. PubMed
  • Li Y, Li X, Stremlau M, Lee M, Sodroski J. Removal of arginine 332 allows human TRIM5alpha to bind human immunodeficiency virus capsids and to restrict infection. J Virol 2006; 80:6738-44. PubMed
  • Perron MJ, Stremlau M, Sodroski J. Two surface-exposed elements of the B30.2/SPRY domain as potency determinants of N-tropic murine leukemia virus restriction by human TRIM5alpha. J Virol 2006; 80:5631-6. PubMed
  • Si Z, Vandegraaff N, O'huigin C, Song B, Yuan W, Xu C, Perron M, Li X, Marasco WA, Engelman A, Dean M, Sodroski J. Evolution of a cytoplasmic tripartite motif (TRIM) protein in cows that restricts retroviral infection. Proc Natl Acad Sci U S A 2006; 103:7454-9. PubMed
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