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    Thomas C Greenough MD

    TitleAssistant Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentMedicine
    AddressUniversity of Massachusetts Medical School
    55 Lake Avenue North
    Worcester MA 01655
    Phone508-856-6282
      Other Positions
      InstitutionUMMS - School of Medicine
      DepartmentPediatrics
      DivisionPediatric Immunology & Infectious Diseases

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentCenter for AIDS Research

        Overview 
        Narrative

        Academic Background

        Education
        Amherst College. Amherst, MA B.A. 1981
        University of Rochester School of Medicine. Rochester, NY M.D. 1987
        Training
        Residency in Internal Medicine 1987-1990
        University Hospital, Boston University School of Medicine - Boston, MA
        Fellowship in Infectious Diseases 1990-1993
        University of Massachusetts Medical Center - Worcester, MA
        Certification
        Internal Medicine 1990
        American Board of Internal Medicine
        Infectious Diseases 1993
        American Board of Internal Medicine

        Research Interests

        Photo:  Thomas C. GreenoughMy broad interest is the pathogenesis of human immunodeficiency virus type 1 (HIV-1). The general approach we have taken is to identify clinical circumstances that may reveal the critical elements of pathogenesis. Our studies look at both virus and host factors that could play a role in the disease process.

        We are examining the rare individuals who show no evidence of disease 10 or more years after infection with HIV-1 without ever having received antiretroviral therapy. We have found evidence that the viruses of many of these long-term non-progressors (LTNP) have unique characteristics (1). We have observed unusual or unique genetic polymorphisms that are difficult for the virus to revert (mainly small deletions or insertions), and are present with uniform consistency over time. We are examining the possibility that these polymorphisms affect the pathogenic potential of the viruses. We also have shown that the LTNP as a group have vigorous cellular immune responses (2). We are developing techniques to measure virus-specific cellular immune responses in order to test the hypothesis that certain immune responses are critical in limiting the growth of virulent strains in the LTNP. With these studies we aim to define the relative importance and functional contribution of individual genetic elements of HIV-1 for pathogenesis in humans. We also seek to identify immune mechanisms by which HIV-1 infection or disease might be controlled.

        We are also examining the predictors of disease progression in individuals on highly active antiretroviral therapy (HAART). Using a sensitive assay to detect 2-LTR circular forms of viral DNA in circulating lymphocytes, we have found evidence that most individuals with undetectable plasma viral RNA still have newly infected cells in the circulation (5). We have enrolled into a longitudinal cohort study individuals who are receiving HAART and who have had undetectable levels of plasma viral RNA for greater than one year. Our primary goal is to identify factors that predict disease progression in this group. We also will attempt to define the residual reservoirs of viral replication in these individuals. With these studies we will gain further insight into HIV-1 pathogenesis in the setting of HAART. These studies may provide new benchmarks for patients and clinicians striving to achieve optimal clinical outcome.



        Bibliographic 
        selected publications
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        1. Alpert MD, Heyer LN, Williams DE, Harvey JD, Greenough T, Allhorn M, Evans DT. A Novel Assay for Antibody-Dependent Cell-Mediated Cytotoxicity against HIV-1- or SIV-Infected Cells Reveals Incomplete Overlap with Antibodies Measured by Neutralization and Binding Assays. J Virol. 2012 Nov; 86(22):12039-52.
          View in: PubMed
        2. Persaud D, Luzuriaga K, Ziemniak C, Muresan P, Greenough T, Fenton T, Blackford A, Ferguson K, Neu N, Cunningham CK. Effect of therapeutic HIV recombinant poxvirus vaccines on the size of the resting CD4+ T-cell latent HIV reservoir. AIDS. 2011 Nov 28; 25(18):2227-34.
          View in: PubMed
        3. Friberg H, Bashyam H, Toyosaki-Maeda T, Potts JA, Greenough T, Kalayanarooj S, Gibbons RV, Nisalak A, Srikiatkhachorn A, Green S, Stephens HA, Rothman AL, Mathew A. Cross-Reactivity and Expansion of Dengue-Specific T cells During Acute Primary and Secondary Infections in Humans. Sci Rep. 2011; 1:51.
          View in: PubMed
        4. Sharkey M, Babic DZ, Greenough T, Gulick R, Kuritzkes DR, Stevenson M. Episomal Viral cDNAs Identify a Reservoir That Fuels Viral Rebound after Treatment Interruption and That Contributes to Treatment Failure. PLoS Pathog. 2011 Feb; 7(2):e1001303.
          View in: PubMed
        5. Greenough TC, Campellone SC, Brody R, Jain S, Sanchez-Merino V, Somasundaran M, Luzuriaga K. Programmed Death-1 expression on Epstein Barr virus specific CD8+ T cells varies by stage of infection, epitope specificity, and T-cell receptor usage. PLoS One. 2010; 5(9):e12926.
          View in: PubMed
        6. Shiu C, Cunningham CK, Greenough T, Muresan P, Sanchez-Merino V, Carey V, Jackson JB, Ziemniak C, Fox L, Belzer M, Ray SC, Luzuriaga K, Persaud D. Identification of ongoing human immunodeficiency virus type 1 (HIV-1) replication in residual viremia during recombinant HIV-1 poxvirus immunizations in patients with clinically undetectable viral loads on durable suppressive highly active antiretroviral therapy. J Virol. 2009 Oct; 83(19):9731-42.
          View in: PubMed
        7. Greenough TC, Cunningham CK, Muresan P, McManus M, Persaud D, Fenton T, Barker P, Gaur A, Panicali D, Sullivan JL, Luzuriaga K. Safety and immunogenicity of recombinant poxvirus HIV-1 vaccines in young adults on highly active antiretroviral therapy. Vaccine. 2008 Dec 9; 26(52):6883-93.
          View in: PubMed
        8. Swingler S, Zhou J, Swingler C, Dauphin A, Greenough T, Jolicoeur P, Stevenson M. Evidence for a pathogenic determinant in HIV-1 Nef involved in B cell dysfunction in HIV/AIDS. Cell Host Microbe. 2008 Jul 17; 4(1):63-76.
          View in: PubMed
        9. Haupt S, Donhauser N, Chaipan C, Schuster P, Puffer B, Daniels RS, Greenough TC, Kirchhoff F, Schmidt B. CD4 binding affinity determines human immunodeficiency virus type 1-induced alpha interferon production in plasmacytoid dendritic cells. J Virol. 2008 Sep; 82(17):8900-5.
          View in: PubMed
        10. Hadinoto V, Shapiro M, Greenough TC, Sullivan JL, Luzuriaga K, Thorley-Lawson DA. On the dynamics of acute EBV infection and the pathogenesis of infectious mononucleosis. Blood. 2008 Feb 1; 111(3):1420-7.
          View in: PubMed
        11. Roberts A, Thomas WD, Guarner J, Lamirande EW, Babcock GJ, Greenough TC, Vogel L, Hayes N, Sullivan JL, Zaki S, Subbarao K, Ambrosino DM. Therapy with a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody reduces disease severity and viral burden in golden Syrian hamsters. J Infect Dis. 2006 Mar 1; 193(5):685-92.
          View in: PubMed
        12. Tripp RA, Haynes LM, Moore D, Anderson B, Tamin A, Harcourt BH, Jones LP, Yilla M, Babcock GJ, Greenough T, Ambrosino DM, Alvarez R, Callaway J, Cavitt S, Kamrud K, Alterson H, Smith J, Harcourt JL, Miao C, Razdan R, Comer JA, Rollin PE, Ksiazek TG, Sanchez A, Rota PA, Bellini WJ, Anderson LJ. Monoclonal antibodies to SARS-associated coronavirus (SARS-CoV): identification of neutralizing and antibodies reactive to S, N, M and E viral proteins. J Virol Methods. 2005 Sep; 128(1-2):21-8.
          View in: PubMed
        13. Greenough TC, Carville A, Coderre J, Somasundaran M, Sullivan JL, Luzuriaga K, Mansfield K. Pneumonitis and multi-organ system disease in common marmosets (Callithrix jacchus) infected with the severe acute respiratory syndrome-associated coronavirus. Am J Pathol. 2005 Aug; 167(2):455-63.
          View in: PubMed
        14. Farrow MA, Somasundaran M, Zhang C, Gabuzda D, Sullivan JL, Greenough TC. Nuclear localization of HIV type 1 Vif isolated from a long-term asymptomatic individual and potential role in virus attenuation. AIDS Res Hum Retroviruses. 2005 Jun; 21(6):565-74.
          View in: PubMed
        15. Greenough TC, Babcock GJ, Roberts A, Hernandez HJ, Thomas WD, Coccia JA, Graziano RF, Srinivasan M, Lowy I, Finberg RW, Subbarao K, Vogel L, Somasundaran M, Luzuriaga K, Sullivan JL, Ambrosino DM. Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice. J Infect Dis. 2005 Feb 15; 191(4):507-14.
          View in: PubMed
        16. Moore MJ, Dorfman T, Li W, Wong SK, Li Y, Kuhn JH, Coderre J, Vasilieva N, Han Z, Greenough TC, Farzan M, Choe H. Retroviruses pseudotyped with the severe acute respiratory syndrome coronavirus spike protein efficiently infect cells expressing angiotensin-converting enzyme 2. J Virol. 2004 Oct; 78(19):10628-35.
          View in: PubMed
        17. Li W, Greenough TC, Moore MJ, Vasilieva N, Somasundaran M, Sullivan JL, Farzan M, Choe H. Efficient replication of severe acute respiratory syndrome coronavirus in mouse cells is limited by murine angiotensin-converting enzyme 2. J Virol. 2004 Oct; 78(20):11429-33.
          View in: PubMed
        18. Hiebenthal-Millow K, Greenough TC, Bretttler DB, Schindler M, Wildum S, Sullivan JL, Kirchhoff F. Alterations in HIV-1 LTR promoter activity during AIDS progression. Virology. 2003 Dec 5; 317(1):109-18.
          View in: PubMed
        19. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003 Nov 27; 426(6965):450-4.
          View in: PubMed
        20. Schindler M, Würfl S, Benaroch P, Greenough TC, Daniels R, Easterbrook P, Brenner M, Münch J, Kirchhoff F. Down-modulation of mature major histocompatibility complex class II and up-regulation of invariant chain cell surface expression are well-conserved functions of human and simian immunodeficiency virus nef alleles. J Virol. 2003 Oct; 77(19):10548-56.
          View in: PubMed
        21. Haran JP, Greenough TC, Luzuriaga K, Sullivan JL, Flanigan T, Somasundaran M. Enhanced culture method for detection of replication-competent virus in peripheral blood mononuclear cells of HIV type 1-infected individuals. AIDS Res Hum Retroviruses. 2002 May 20; 18(8):577-83.
          View in: PubMed
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