Research Knowledgebase

Glen N. Barber, Ph.D. Professor of Medicine, Eugenia J. Dodson Chair in Cancer Research, and Associate Director of Basic Science View full faculty profile

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.

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. PubMed link

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. PubMed link

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. PubMed link

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. PubMed link

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. PubMed link

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

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

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. PubMed link

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. PubMed link

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. PubMed link

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. PubMed link

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. PubMed link

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. PubMed link

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. PubMed link

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. PubMed link

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

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. PubMed link

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. PubMed link

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. PubMed link

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. PubMed link

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. PubMed link

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. PubMed link

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. PubMed link

Leader of Multidisciplinary Research Program, Viral Oncology Program.