Alan Rothman, M.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Infectious Diseases and Immunology
   Medicine

Other Affiliation(s):
   Center for AIDS Research
   Center for Infectious Disease and Vaccine Research
   Clinical and Population Health Research
   Program in Immunology and Virology

Immunopathogenesis of Virus Diseases

My laboratory is studying the role of virus-specific T lymphocytes in the clinical manifestations of virus diseases. Dengue virus and hepatitis C virus (HCV) are the topics of our current research.

Dengue: We are participating in several international collaborative clinical studies to define the risk factors for and pathophysiology of severe dengue disease in humans. In one study, we are analyzing the kinetics of viral replication, T cell and monocyte activation, and cytokine production in children with acute dengue virus infections. In another study, we are defining immunologic responses prior to dengue infection that are associated with an increased risk for severe disease. We are also using laboratory mice as a model of the T lymphocyte response to dengue infection.

Model of dengue hemorrhagic fever pathogenesis

Click here to access an on-line seminar on dengue:

Hepatitis C: We are studying CTL responses in patients with chronic HCV infections and their association with hepatic inflammation and viral persistence. We are isolating HCV-specific CTL from liver tissue and blood specimens of patients and analyzing their recognition of endogenous viral sequences.

Recent Publications

Journal articles| Book Chapters and Other Media

Journal articles:

Click here for articles freely available on eScholarship@UMMS.

The author lists are linked to the PubMed abstract of each article.

• Terajima M, Orphin L, Leporati AM, Pazoles P, Cruz J, Rothman AL, Ennis FA.Vaccinia virus-specific CD8+ T cell responses target a group of epitopes without a strong immunodominance hierarchy in humans. Human Immunol 2008; 69:815-825.
• Mammen MP Jr, Pimgate C, Koenraadt CJM, Rothman AL, Aldstadt J, Nisalak A, Ypil-Butac CA, Klungthong C, Thaisomboonsuk B, Jarman RG, Jones JW, Zhang C, Srikiatkhachorn A, Gibbons RV, Thammapalo S, Getis A, Endy TP, Morrison AC, Libraty DH, Ennis FA, Green S, Scott TW.Spatial and temporal focality of dengue virus transmission in Thai villages revealed by cluster investigations. PLoS Med 2008; 5:e205.
• Mathew A, Rothman AL.Understanding the contribution of cellular immunity to dengue disease pathogenesis. Immunol Rev 2008; 225:300-313.
• Mathew A, O’Bryan J, Marshall W, Terajima M, Green S, Rothman AL, Ennis FA.Robust intrapulmonary CD8 T cell responses with N1L deleted but not wild type vaccinia viruses. PLoS ONE 2008; 3:e3323.
• Potts JA, Rothman AL.Clinical and laboratory features that distinguish dengue from other febrile illnesses in endemic populations: a systematic review. Trop Med Int Health 2008; 13:1328-1340.
• Nightingale ZN, Patkar C, Rothman AL.Viral replication and paracrine effects result in distinct functional responses of dendritic cells following infection with dengue 2 virus. J Leukoc Biol 2008; 84:1028-1038.
• Pavlin JA, Hickey AC, Ulbrandt N, Chan YP, Endy TP, Boukhvalova MS, Chunsuttiwat S, Nisalak A, Libraty DH, Green S, Rothman AL, Ennis FA, Jarman R, Gibbons RV, Broder CC.Human metapneumovirus reinfection among children in Thailand determined by an enzyme-linked immunosorbent assay using purified soluble fusion protein. J Infect Dis 2008; 198:836-842.
• Kennedy JS, Co M, Green S, Longtine K, Longtine J, O’Neill MA, Adams JP, Rothman AL, Yu Q, Johnson-Leva R, Pal R, Wang S, Lu S, Markham P.The safety and tolerability of an HIV-1 DNA prime-protein boost vaccine (DP6-001) in healthy adult volunteers. Vaccine 2008; 4420-4424.
• Warke RV, Becerra A, Zawadzka A, Schmidt DJ, Martin KJ, Giaya K, Dinsmore JH, Woda M, Hendricks G, Levine T, Rothman AL, Bosch I. Efficient dengue virus (DENV) infection of human muscle satellite cells upregulates type I interferon response genes and differentially modulates MHC I expression on bystander and DENV-infected cells. J Gen Virol 2008; 89:1605-1615.
• Jarman RG, Holmes EC, Rodpradit P, Klungthong C, Gibbons RV, Nisalak A, Rothman AL, Libraty DH, Ennis FA, Mammen MP Jr, Endy TP. Microevolution of dengue viruses circulating among primary school children in Kamphaeng Phet, Thailand. J Virol 2008; 82:5494-5500.
• Co MD, Orphin L, Cruz J, Pazoles P, Rothman AL, Ennis FA, Terajima M. Discordance between antibody and T cell responses in recipients of trivalent inactivated influenza vaccine. Vaccine 2008; 26:1990-1998.
• Beaumier CM, Mathew A, Bashyam HS, Rothman AL. Cross-reactive memory CD8(+) T cells alter the immune response to heterologous secondary dengue virus infections in mice in a sequence-specific manner. J Infect Dis 2008; 197:608-617.
• Wang S, Kennedy JS, West K, Montefiori DC, Coley S, Lawrence J, Shen S, Green S, Rothman AL, Ennis FA, Arthos J, Pal R, Markham P, Lu S. Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime-protein boost HIV-1 vaccine in healthy human volunteers. Vaccine 2008; 26:3947-3957.
• Becerra A, Warke RV, de Bosch N, Rothman AL, Bosch I. Elevated levels of soluble ST2 protein in dengue virus infected patients. Cytokine 2008; 41:114-120.
• Hatch S, Mathew A, Rothman AL.Dengue vaccine: opportunities and challenges. IDrugs 2008; 11:42-45.
• Warke RV, Martin KJ, Giaya K, Shaw SK, Rothman AL, Bosch I. TRAIL is a novel antiviral protein against dengue virus. J Virol 2008; 82:555-564.
• Libraty DH, Myint KS, Murray CK, Gibbons RV, Mammen MP, Endy TP, Li W, Vaughn DW, Nisalak A, Kalayanarooj S, Hospenthal DR, Green S, Rothman AL, Ennis FA. A comparative study of leptospirosis and dengue in Thai children. PLoS Negl Trop Dis 2007; 1:e111.
• Anderson KB, Chunsuttiwat S, Nisalak A, Mammen MP, Libraty DH, Rothman AL, Green S, Vaughn DW, Ennis FA, Endy TP. Burden of symptomatic dengue infection in children at primary school in Thailand: a prospective study. Lancet 2007; 369:1452-1459.
• Srikiatkhachorn A, Kruatrachue A, Ratanaprakarn W, Wongtapradit L, Nithipanya N, Kalayanarooj S, Nisalak A, Thomas SJ, Gibbons RV, Mammen MP, Libraty DH, Ennis FA, Rothman AL, Green S. Natural history of plasma leakage in dengue hemorrhagic fever: a serial ultrasonographic study. Pediatr Infect Dis J 2007; 26:283-290.
• Laoprasopwattana K, Libraty DH, Endy TP, Nisalak A, Chunsuttiwat S, Ennis FA, Rothman AL, Green S. Antibody dependent cellular cytotoxicity mediated by plasma obtained before secondary dengue virus infections: potential involvement in early control of viral replication. J Infect Dis 2007; 195:1108-1116.
• Srikiatkhachorn A, Ajariyakhajorn C, Endy TP, Kalayanarooj S, Libraty DH, Green S, Ennis FA, Rothman AL. Virus-induced decline in soluble vascular endothelial growth factor receptor-2 is associated with plasma leakage in dengue hemorrhagic fever. J Virol 2007; 81:1592-1600.
• Cardier JE, Rivas B, Romano E, Rothman AL, Perez-Perez C, Ochoa M, Caceres AM, Cardier M, Guevara N, Giovannetti R. Evidence of vascular damage in dengue disease: demonstration of high levels of soluble cell adhesion molecules and circulating endothelial cells. Endothelium 2006; 13:353-358.
• Green S, Rothman A. Immunopathological mechanisms in dengue and dengue hemorrhagic fever. Curr Opin Infect Dis 2006; 19:429-436.
• Myint KS, Endy TP, Mongkolsirichaikul D, Manomuth C, Kalayanarooj S, Vaughn DW, Nisalak A, Green S, Rothman AL, Ennis FA, Libraty DH. Cellular immune activation in children with acute dengue virus infections is modulated by apoptosis. J Infect Dis 2006; 194:600-607.
• Cardier JE, Balogh V, Perez-Silva C, Romano E, Rivas B, Bosch N, Rothman AL. Relationship of thrombopoietin and interleukin-11 levels to thrombocytopenia associated with dengue disease. Cytokine 2006; 34:155-160.
• Medin CL, Rothman AL. Cell type-specific mechanisms of IL 8 induction by dengue virus and differential response to drug treatment. J Infect Dis 2006; 193:1070-1077.
• Morishima C, Polyak SJ, Ray R, Doherty MC, Di Bisceglie AM, Malet PF, Bonkovsky HL, Sullivan DG, Gretch DR, Rothman AL, Koziel MJ, Lindsay KL, HALT-C Trial Group. Hepatitis C virus-specific immunity and quasispecies variability at baseline are associated with non-response to antiviral therapy in advanced hepatitis C. J Infect Dis 2006; 193:931-940.
• Bashyam HS, Green S, Rothman AL. Dengue virus-reactive CD8+ T cells display quantitative and qualitative differences in their response to variant epitopes of heterologous viral serotypes. J Immunol 2006; 176:2817-2824.

Book Chapters and Other Media:

• Marglin S, Rothman AL. A 54-year-old man with fever and rash after travel to the Caribbean. In: Heffner JE, Sahn SA (eds.) Internal Medicine Pearls (2nd edition). Hanley & Belfus, Philadelphia, 2000. p. 216-218.
• Green S, Rothman AL. West Nile virus. In: Gorbach SL, Bartlett JG, Blacklow NR (ed.) Infectious Diseases (3rd edition). Lippincott Williams & Wilkins, Philadelphia, 2003. p. 2128-2132.
• Rothman AL. Bacterial meningitis. In: Irwin RS, Rippe JM (eds.) Manual of Intensive Care Medicine (4th edition). Lippincott Williams & Wilkins, Philadelphia, 2005.
• Rothman AL. Central nervous system infections. In: Irwin RS, Rippe JM (eds.) Intensive Care Medicine (6th edition). Lippincott Williams & Wilkins, Philadelphia, 2008. p. 1044-1054.
• Rothman AL. Pathogenesis of dengue virus infections. In: Rose BL (ed.) UpToDate. Waltham, MA.
• Rothman AL. Prevention and treatment of dengue virus infections. In: Rose BL (ed.) UpToDate. Waltham, MA.
• Rothman AL. Clinical presentation and diagnosis of dengue virus infections. In: Rose BL (ed.) UpToDate. Waltham, MA.
• Rothman AL. Epidemiology of dengue virus infections. In: Rose BL (ed.) UpToDate. Waltham, MA.
  

Potential Rotation Projects

• Flavivirus-specific T lymphocytes- isolation of T lymphocytes (human or murine) with novel specificities for epitopes of dengue virus or hepatitis C virus; functional characterization of T cell effector responses; quantitation of epitope-specific CD4 and/or CD8 T cells; molecular analysis of virus-specific T cell receptor genes



• In vitro replication of dengue virus- viral binding; viral replication in primary human cells



• Flavivirus proteins- cloning and expression of flavivirus genes; analysis of protein function in vitro

Academic Background

Education:

• B.A., Boston University, 1979
• M.D., Boston Universtiy, 1983

Post-Graduate Training:

• Internal Medicine- Medical College of Virginia, 1983-85; Boston V.A. Hospital, 1985-86
• Infectious Diseases- University of Massachusetts Medical Center, 1986-89

Board Certification:

• Diplomate, American Board of Internal Medicine, 1986
• Diplomate, American Board of Internal Medicine (Infectious Diseases), 1988

Honors and Awards:

• Phi Beta Kappa
• Alpha Omega Alpha

Office: S6-755a
Phone: 508-856-6976
Fax: 508-856-4890
E-mail: Alan.Rothman@umassmed.edu
Keywords: T lymphocytes, Biodefense, Viral Pathogenesis, Emerging Infectious Diseases, Viral Infections and Immunity

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