Glen N. Barber, Ph.D.

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Glen N. Barber, Ph.D.

Professor of Medicine, Eugenia J. Dodson Chair in Cancer Research, and Associate Director of Basic Science

Description of Research


Dr. Barber's research focuses on understanding the mechanisms of innate immunity to viral infection and malignant disease. Gaining insight into the innate immune process allows investigators to develop translational research comprising the design of novel vaccines and therapeutics to combat disease. One of the laboratory's interests is analyzing the function of interferons "IFNs", which can be activated following virus infection. IFNs are secreted from the cell, and following interaction with specific receptors, mediate their action by inducing the expression of numerous genes, many of which exert potent antiviral and antitumor activity. Recently, Dr. Barber's laboratory discovered a new mechanism responsible for the induction of the IFNs. Researchers demonstrated that activation of IFN required 'death domain' containing proteins such as receptor interacting protein 1 "RIP1" and the Fas-associated death domain molecule "FADD". Other ongoing research focuses on further understanding the mechanisms of RNA-mediated innate immune signaling in the cell, which could allow for the potential development of new strategies to stimulate the host immune response. These studies revealed that immune antiviral system appeared defective in tumor cells. Accordingly, studies indicated that viruses such as vesicular stomatitis virus "VSV", a relatively non-pathogenic RNA virus, can selectively induce the killing of malignant cells, but not normal cells. Genetically engineered VSV's now have been generated by the laboratory and are being evaluated as a novel approach to cancer therapy. Dr. Barber also is interested in studying how viruses such as the hepatitis C virus, Epstein-Barr virus "EBV", human papillomavirus "HPV", and human herpes virus type-8 "HHV-8" contribute towards tumorigenesis, which may involve inhibiting innate immune pathways to avoid host defense countermeasures. Understanding the mechanisms involved in these processes could lead to an improvement of current therapies as well as the identification of new therapeutic targets and of malignant disease involving these viruses.

Highlights / Discoveries

  • Discovered a new innate immune recognition pathway. This pathway is important in recognizing virus infection and for activating host defense countermeasures. Unraveling this pathway will shed new insight into how to develop novel ways to combat disease.
  • Discovered vesicular stomatitis virus "VSV" potent oncolytic "anti-tumor" properties. Dr. Barber's laboratory has shown that VSV replicates to high levels in tumorigenic cells "but not normal cells", and have identified defects in IFN signaling and translational control in tumorigenic cells as possible reasons for this uncontrolled replication.
  • Developed recombinant VSV that express other virus proteins, such as from hepatitis C virus and human papillomavirus "implicated in tumorigenesis" as possible vaccines for these viruses.

    • Selected Cancer-Related Publications

    Parisien JP, Bamming D, Komuro A, Ramachandran A, Rodriguez JJ, Barber G, Wojahn RD, Horvath CM. A shared interface mediates paramyxovirus interference with antiviral RNA helicases MDA5 and LGP2. J Virol 83:7252-60, 2009. Read the publication »

    Barber GN. The NFAR's (nuclear factors associated with dsRNA): Evolutionarily conserved members of the dsRNA binding protein family. RNA Biol 6:35-39, 2009. Read the publication »

    Barral PM, Sarkar D, Su ZZ, Barber GN, Desalle R, Racaniello VR, Fisher PB. Functions of the cytoplasmic RNA sensors RIG-I and MDA-5: Key regulators of innate immunity. Pharmacol Ther 124:219-34, 2009. Read the publication »

    Willmon CL, Saloura V, Fridlender ZG, Wongthida P, Diaz RM, Thompson J, Kottke T, Federspiel M, Barber G, Albelda SM, Vile RG. Expression of IFN-beta enhances both efficacy and safety of oncolytic vesicular stomatitis virus for therapy of mesothelioma. Cancer Res 69:7713-20,2009. Read the publication »

    Chakraborty P, Seemann J, Mishra RK, Wei JH, Weil L, Nussenzveig DR, Heiber J, Barber GN, Dasso M, Fontoura BM. Vesicular stomatitis virus inhibits mitotic progression and triggers cell death. EMBO Rep 10:1154-60,2009. Read the publication »

    Ishikawa H, Ma Z, Barber GN. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 461:788-92,2009. Read the publication »

    Ishikawa H, Barber GN. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 455:674-8, 2008. Read the publication »

    Pfeifer I, Elsby R, Fernandez M, Faria PA, Nussenzveig DR, Lossos IS, Fontoura BM, Martin WD, Barber GN. NFAR-1 and -2 modulate translation and are required for efficient host defense. Proc Natl Acad Sci U S A 105:4173-8, 2008. Read the publication »

    Kottke T, Galivo F, Wongthida P, Maria Diaz R, Thompson J, Jevremovic D, Barber GN, Hall G, Chester J, Selby P, Harrington K, Melcher A, Vile RG. Treg Depletion-enhanced IL-2 Treatment Facilitates Therapy of Established Tumors Using Systemically Delivered Oncolytic Virus. Mol Ther 16:1217-26, 2008. Read the publication »

    Pfeifer I, Elsby R, Fernandez M, Faria PA, Nussenzveig DR, Lossos IS, Fontoura BM, Martin WD, Barber GN. NFAR-1 and -2 modulate translation and are required for efficient host defense. Proc Natl Acad Sci U S A. Mar 2008 18;105(11):4173-8. Read the publication »

    Hickman HD, Takeda K, Skon CN, Murray FR, Hensley SE, Loomis J, Barber GN, Bennink JR, Yewdell JW. Direct priming of antiviral CD8+ T cells in the peripheral interfollicular region of lymph nodes. Nature Immunology. 2008 Feb;9(2):155-65. Read the publication »

    Qiao J, Kottke T, Willmon C, Galivo F, Wongthida P, Diaz RM, Thompson J, Ryno P, Barber GN, Chester J, Selby P, Harrington K, Melcher A, Vile RG. Purging metastases in lymphoid organs using a combination of antigen-nonspecific adoptive T cell therapy, oncolytic virotherapy and immunotherapy. Nature Medicine. 2008 Jan;14(1):37-44. Read the publication »

    Kottke T, Diaz RM, Kaluza K, Pulido J, Galivo F, Wongthida P, Thompson J, Willmon C, Barber GN, Chester J, Selby P, Strome S, Harrington K, Melcher A, Vile RG. Use of biological therapy to enhance both virotherapy and adoptive T-cell therapy for cancer. Mol Ther 16:1910-8, 2008. Read the publication »

    Radtke AL, Delbridge LM, Balachandran S, Barber GN, O'Riordan MX. TBK1 Protects Vacuolar Integrity during Intracellular Bacterial Infection. PLoS Pathog 3:e29,2007. Read the publication »

    Andrews NP, Pack CD, Vezys V, Barber GN, Lukacher AE. Early virus-associated bystander events affect the fitness of the CD8 T cell response to persistent virus infection. J Immunol;178(11): 7267-75,2007. Read the publication »

    Greidinger EL, Zang Y, Martinez L, Jaimes K, Nassiri M, Bejarano P, Barber GN, Hoffman, RW. Differential tissue targeting of autoimmunity manifestations by Autoantigen-Associated Y RNAs. Arthritis Rheum; 56:1589-97,2007. Read the publication »

    Goodman AG, Smith JA, Balachandran S, Perwitasari O, Proll SC, Thomas MJ, Korth MJ, Barber GN, Schiff LA, Katze MG. The Cellular Protein P58IPK Regulates Influenza Virus mRNA Translation and Replication through a PKR-Mediated Mechanism. J Virol; 81:2221-30,2007. Read the publication »

    Diaz RM, Galivo F, Kottke T, Wongthida P, Qiao J, Thompson J, Valdes M, Barber GN, Vile RG. Oncolytic immunovirotherapy for melanoma using vesicular stomatitis virus. Cancer Res 67:2840-8,2007. Read the publication »

    Venkataraman T, Valdes M, Elsby R, Kakuta S, Caceres G, Saijo S, Iwakura Y, Barber GN. Loss of DExD/H Box RNA Helicase LGP2 Manifests Disparate Antiviral Responses. J Immunol; 178:6444-55,2007. Read the publication »

    von Holzen U, Pataer A, Raju U, Bocangel D, Vorburger SA, Liu Y, Lu X, Roth JA, Aggarwal BB, Barber GN, Keyomarsi K, Hunt KK, Swisher SG. The Double-Stranded RNA-Activated Protein Kinase Mediates Radiation Resistance in Mouse Embryo Fibroblasts through Nuclear Factor {kappa}B and Akt Activation. Clin Cancer Res 13:6032-9, 2007. Read the publication »

    Venkataraman T, Valdes M, Elsby R, Kakuta S, Caceres G, Saijo S, Iwakura Y, Barber GN. Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses. J Immunol. 2007 May 15;178(10):6444-55. Read the publication »

    Balachandran S, Venkataraman T, Fisher PB, Barber GN. Fas-associated death domain-containing protein-mediated antiviral innate immune signaling involves the regulation of Irf7. J Immunol. 2007 Feb 15;178(4):2429-39. Read the publication »

    Sarkar D, Park ES, Barber GN, Fisher PB. Activation of Double-Stranded RNA Dependent Protein Kinase,A New Pathway by Which Human Polynucleotide Phosphorylase (hPNPaseold-35) Induces Apoptosis. Cancer Res 67:7948-7953, 2007. Read the publication »

    Programs

    Leader of the Multidisciplinary Research Program: Viral Oncology Program