Robert Finberg, M.D.

Academic Role: Professor

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

Other Affiliation(s):
   Cancer Center
   Center for AIDS Research
   Interdisciplinary Graduate Program
   Program in Immunology and Virology

Host-microbial interactions 

Dr. Finberg’s laboratory works on the relationships between host cell surface proteins and viruses and bacteria, and the basis of cellular activation mediated by cell surface proteins.

1. Virus receptor proteins (and viral pathogenesis):
       Because of their well-defined genetics and spacious capsid, adenoviruses can be used to inject new genetic material into stem cells or, potentially, into tumor cells. The laboratory has defined the virus receptor protein for most adenoviruses, as well as the Coxsackie B group viruses (1,2). The use of several transgenic CAR expressing mouse strains are being studied and a CAR knock-out being created.
2. Viral genes and the host: induction of virus specific immune responses:
       The laboratory has pioneered in defining a major role for "pattern recognition proteins" CD 14 and Toll-like receptors in viral pathogenesis andimmunity (3,4).
3. Host cell surface proteins and the basis of cellular activation events:
      The laboratory has studied the mechanism of signal transduction by non-membrane spanning glycosylphosphatidylinositol (GPI) anchored, cell surface proteins. GPI anchored cell surface proteins are important signal transducing proteins. Recent investigations have led to the definition of the cell surface interactions between bacterial lipopolysaccharide (lps) that results in triggering the cytokine release that leads to septic shock. Experiments have focused on the definition of the role of CD14 and the Toll like receptor (TLR) proteins and their interactions in virus and bacterial induced signal transduction events (5).

Representative Publications

Bergelson JM, Cunningham JA, Droguett G, Kurt-Jones E, Krithivas A, Hong JS, Horwitz MS, Crowell RL, Finberg RW. Isolation of a Common Receptor for Coxsackie B viruses and Adenoviruses 2 and 5. Science 1997.

Bergelson JM, Krithivas A, Celi L, Droguett G, Horwitz MS, Wickham T, Crowell RL, Finberg RW. The murine CAR homolog is a receptor for coxsackie B viruses and adenoviruses. J Virol 72:415-9, 1998.

Brubaker JO, Thompson CM, Morrison LA, Knipe DM, Siber GR, and Finberg RW. Th1-Associated Immune Responses to b-Galactosidase Expressed by a Replication-Defective Herpes Simplex Virus. J Immunol 157:1598-1604, 1996.

Marshall WL, Datta R, Hanify K, Teng E, Finberg RW. U937 cells overexpressing bcl-xl are resistant to human immunodeficiency virus-1-induced apoptosis and human immunodeficiency virus-1 replication.  Virology 256:1-7, 1999.

Marshall WL, Yim C, Gustafson E, Graf T, Sage DR, Hanify K, Williams L, Fingeroth J, Finberg RW. Epstein-Barr virus encodes a novel homolog of the bcl-2 oncogene that inhibits apoptosis and associates with Bax and Bak. J Virol 73:5181-5, 1999.

Compton T, Kurt-Jones EA, Boehme KW, Belko J, Latz E, Golenbock DT, Finberg RW. Human cytomegalovirus activates inflammatory cytokine responses via CD14 and toll-like receptor 2. J Virol 2003;77(8):4588-96.

Chen JW, Ghosh R, Finberg RW, Bergelson JM. Structure and chromosomal localization of the murine  coxsackievirus and adenovirus receptor gene. DNA Cell Biol. 2003;22(4):253-9.

Sandor F, Latz E, Re F, Mandell L, Repik G, Golenbock DT, Espevik T, Kurt-Jones EA, Finberg RW. Importance of extra- and intracellular domains of TLR1 and TLR 2 in NF-kB signaling.  J Cell Biol 2003;162(6):1099-1110.

Solomon KR, Sharma P, Chan M, Morrison PT, Finberg RW. CD109 represents a novel branch of the a2-macroglobulin /complement gene family. Gene 2004; 327(2):171-83.

Kurt-Jones EA, Mandell L, Cerny A, Chan M, Zhou S, Wang J, Reed G, Bronson R, Arnold MM, Knipe DM, Finberg RW. Herpes Simplex Virus-1 Interaction with TLR2 Contributes to Lethal Encephalitis. PNAS 2004; 101(5):1315-20.

Finberg RW, Moellering R, Tally F, Craig W, Pankey GA, Dellinger EP, West M, Joshi M, Linden P, Rolston K, Rotschafer JC, Rybak MJ. The importance of bactericidal drugs: Future directions in infectious disease.  Clin Inf Dis. 2004; 39:1314-20.

Dolganiuc A, Oak S, Kodys K, Golenbock DT, Finberg RW, Kurt-Jones EA, Szabo G. Hepatitis C core and nonstructural 3 proteins trigger toll-like receptor 2-mediated pathways and inflammatory activation. Gastroenterol. 2004;127(5):1513-24.

Finberg RW, Re F, Popova L, Golenbock DT, Kurt-Jones EA. Cell activation by Toll like receptors: Role of LBP and CD14. J Endotox Res. 2004;10(6):413-8.

Kurt-Jones EA, Sandor F, Ortiz Y, Bowen GN, Counter SL, Wang TC, Finberg RW. Use of murine embryonic fibroblasts to define toll-like receptor activation and specificity.  J Endotox Res. 2004; 10(6):419-24.

Finberg RW, Kurt-Jones EA. Viruses and TLRs. Microbes and Infection. 2004;6(15):1356-60.

Finberg RW. Role of Toll like receptors in neonatal herpes simplex infection.  J Inf Dis. 2005; 191(5):746-8.

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 Inf Dis. 2005;191(4):507-14.

Zhou S, Kurt-Jones EA, Mandell L, Cerny A, Chan M, Golenbock DT, Finberg RW.  MyD88 is critical for the development of innate and adaptive immunity during Lymphocytic Choriomeningitis Virus Infection. Eur J Immunol. 2005;35(3):822-30.

Repik A, Pincus SE, Ghiran I, Nicholson-Weller A, Asher DR, Cerny A, Casey LS, Jones SM, Jones SN, Mohamed N, Klickstein LB, Spitalny G, Finberg RW. A transgenic mouse model for studying the clearance of blood-borne pathogens via human complement receptor 1 (CR1). Clin Exp Immunol. 2005;140(2):230-40.

Asher DR, Cerny AM, Weiler SR, Horner JW, Keeler ML, Neptune MA, Jones SN, Bronson RT, DePinho RA, Finberg RW.  The coxsackievirus and adenovirus receptor plays an essential role in cardiomyocyte development.  Genesis. 2005; 42(2):77-85.

Divanovic S, Trompette A, Atabani SF, Madan R, Golenbock DT, Visintin A, Finberg RW, Tarakhovsky A, Vogel SN, Belkaid Y, Kurt-Jones EA, Karp CL. Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105. Nat Immunol. 2005; 6(6):571-8.

Asher DR, Cerny AM, Finberg RW. The erythrocyte viral trap: Transgenic expression of viral receptor on erythrocytesattenuates coxsackievirus B infection. PNAS 2005;102(36):12897-902.

Finberg RW, Knipe DM, Kurt-Jones EA. Herpes Simplex virus and Toll-like Receptors. Viral Immunol. 2005;18(3):457-65.

Wang JP, Kurt-Jones EW, Shin OS, Manchak MD, Levin MJ, Finberg RW. Varicella-zoster virus activates inflammatory cytokines in human monocytes and macrophages via Toll-like receptor 2. J Virol. 2005;79(20):12658-66.

Szomolanyi-Tsuda E, Liang X, Welsh RM, Kurt-Jones EA, Finberg RW. Role for TLR2 in NK cell-mediated control of murine cytomegalovirus in vivo. J Virol. 2006;80(9):4286-91.

Wang JP, Liu P, Latz E, Golenbock DT, Finberg RW, Libraty DH. Abstract  Flavivirus activation of plasmacytoid dendritic cells delineates key elements of TLR7 signaling beyond endosomal recognition. J Immunol. 2006;177(10):7114-21.

Finberg RW, Kurt-Jones EA. CD14: chaperone or matchmaker? Immunity. 2006;24(2):127-9.

Finberg RW, Wang JP, Kurt-Jones EA. Toll like receptors and viruses. Rev Med Virol. 2007;17(1):35-43.

Zhou S, Kurt-Jones EA, Fitzgerald KA, Wang JP, Cerny AM, Chan M, Finberg RW. Cutting Edge: Antibody-mediated TLR7-dependent recognition of viral RNA. J Immunol. 2007 Mar 15;178(6):3363-7.

Zhou S, Kurt-Jones EA, Fitzgerald KA, Wang JP, Cerny AM, Chan M, Finberg RW. Role of MyD88 in route-dependent susceptibility to vesicular stomatitis virus infection. J Immunol. 2007 Apr 15;178(8):5173-81.

Wang JP, Kurt-Jones EA, Finberg RW. Innate immunity to respiratory viruses. Cell Microbiol. 2007 Jul;9(7):1641-6.

Finberg RW, Kurt-Jones EA. Tolls: you pay them on the way in and on the way out! J Infect Dis. 2007 Aug 15;196(4):497-8.

Zhou S, Halle A, Kurt-Jones EA, Cerny AM, Porpiglia E, Rogers M, Golenbock DT, Finberg RW. Lymphocytic choriomeningitis virus (LCMV) infection of CNS glial cells results in TLR2-MyD88/Mal-dependent inflammatory responses. J Neuroimmunol. 2008 Feb;194(1-2):70-82.

Wang JP, Bowen GN, Padden C, Cerny A, Finberg RW, Newburger PE, Kurt-Jones EA. Toll-like receptor-mediated activation of neutrophils by influenza A virus. Blood. 2008 Sep 1;112(5):2028-34.

Murawski MR, Bowen GN, Cerny AM, Anderson LJ, Haynes LM, Tripp RA, Kurt-Jones EA, Finberg RW. RSV Activates Innate Immunity through Toll-like Receptor 2. J Virol. 2008 Nov 19.

Zhou S, Kurt-Jones EA, Cerny AM, Chan M, Bronson RT, Finberg RW. MyD88 intrinsically regulates CD4 T cell responses. J Virol. 2008 Dec 3.

Seiradake E, Henaff D, Wodrich H, Billet O, Perreau M, Hippert C, Mennechet F, Schoehn G, Lortat-Jacob H, Dreja H, Ibanes S, Kalatzis V, Wang JP, Finberg RW, Cusack S, Kremer EJ. The Cell Adhesion Molecule "CAR" and Sialic Acid on Human Erythrocytes Influence Adenovirus In Vivo Biodistribution. PLoS Pathog. 2009 Jan;5(1).

Rotation Project Background

Dr. Finberg's research is in the area of host-microbial interactions. He is working on defining cell surface proteins that control the host responses to bacteria and viruses. He is characterizing the role of CD14 and the Toll-like proteins which are "pattern recognition" proteins involved in the immune response to many different microbial antigens. In addition he is working out the pathway for viral entry into cells and how that pathway can be exploited for gene delivery. His work in infections has led him to investigate the association between viruses and cancer and to develop new methods for enhancing the immune responses to viruses to eliminate virus associated malignancies.

Potential Rotation Projects

1. Virus receptor proteins (and viral pathogenesis):
   Because of their well defined genetics and spacious capsid, adenoviruses can be used to inject new genetic material into stem cells or, potentially, into tumor cells. The laboratory has defined the virus receptor protein for most adenoviruses, as well as the Coxsackie B group viruses . The use of several transgenic CAR expressing mouse strains are being studied and a CAR knock-out being created.



2. Viral genes and the host: induction of virus specific immune responses:
   The laboratory has demonstrated that viruses can be used as vectors to produce long-lasting immunity to defined antigens suggesting the possibility of new vaccine approaches to HIV-1 and other pathogens. In addition the laboratory has defined both viral proteins that affect cell death (and may lead to tumorigenesis) as well as cell proteins that result in viral persistence. The induction of immunity to herpesviruses (especially EBV) as a means of treating virus-associated malignancy is an ongoing project.



3. Host cell surface proteins and the basis of cellular activation events:
   The laboratory has studied the mechanism of signal transduction by non-membrane spanning glycosylphosphatidylinositol (GPI) anchored, cell surface proteins. GPI anchored cell surface proteins are important signal transducing proteins. Recent investigations have led to the definition of the cell surface interactions between bacterial lipopolysaccharide (lps) that results in triggering the cytokine release that leads to septic shock. Recent experiments have focussed on the definition of the role of the GPI anchored protein and the Toll like receptor (TLR) proteins in virus and bacterial induced signal transduction events.

Academic/Clinical Background:

Education:

• A.B., University of Chicago, 1971
• M.D., Albert Einstein College of Medicine, 1974
• M.A. (Hon.), Harvard University, 1996

Post-Graduate Training:

• Resident, Internal Medicine, Bellevue Hospital, New York, NY, 1974-1977
• Research Fellow in Pathology, Harvard Medical School, Boston, MA, 1977-1978
• Research Fellow in Medicine, Harvard Medical School, Boston, MA, 1978-1979
• Research/Clinical Fellow in Medicine, Peter Bent Brigham Hospital, Boston, MA, 1978-1979
• Clinical Fellow in Medicine (Infectious Diseases), Peter Bent Brigham Hospital, Boston, MA, 1978-1980
• Clinical Fellow in Medicine, Harvard Medical School, Boston, MA, 1979-1980

Board Certification:

• American Board of Internal Medicine, 1976
• American Board of Internal Medicine (Infectious Diseases), 1980

Honors and Awards:

• Alpha Omega Alpha
• Hartford Foundation Award
  
  
• Scholar of the Leukemia & Lymphoma Society

Office: Research 228
Phone: 508-856-1886
Fax: 508-856-6176
E-mail: Robert.Finberg@umassmed.edu
Keywords: Immunology, Clinical Research, Infectious Disease

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