Faculty : Departmental- Primary

Glen N. Barber, Ph.D.

Dr. Barber’s research focuses on understanding mechanisms of innate immunity to virus 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 these diseases. One of the laboratory’s interests involves analyzing the function of interferons (IFNs), which can be produced in response to virus infection. The IFNs are secreted from the cell, and following interaction with specific cellular receptors, mediate their action by inducing the expression of numerous genes, many of which exert potent antiviral and antitumor activity.

Dr. Barber’s laboratory has been responsible for discovering mechanisms that help explain how IFN production is triggered in response to infection by microbes. In 2004 researchers from his laboratory demonstrated that activation of IFN required the ‘death domain’ containing proteins receptor interacting protein 1 (RIP1) and the Fas-associated death domain molecule (FADD). FADD/RIP1 interactions facilitate RLR (Rig-I like Receptor) pathways essential triggering host defense countermeasures in response to infection with RNA viruses, such as vesicular stomatitis virus (VSV) and influenza virus. Recently, Dr. Barber’s laboratory has also elucidated how the cell responds to infection by DNA pathogens such as cancer causing viruses, intracellular bacteria and perhaps certain parasites. A molecule in his lab, referred to as STING (Stimulator of IFN genes) was found to be essential for producing IFN in response to a variety of DNA pathogens. Mice lacking STING are extremely sensitive to virus infection. The importance of STING in innate immunity, cancer and autoimmunity is presently ongoing. Finally, the laboratory has demonstrated another important component of host defense involving molecules called the NFAR (nuclear factors associated with dsRNA). These proteins were found to prevent virus replication by blocking protein synthesis. Understanding mechanisms of innate immune signaling in the cell could enable the development of new strategies to inhibit pathogen replication as well as stimulate the host immune response to avoid disease.

Interestingly, these studies revealed that the innate immune system appeared defective in many types of tumor cells. Accordingly, studies indicated that viruses such as VSV, a relatively non-pathogenic RNA virus, can selectively replicate in and induce the killing of malignant cells, but not normal cells. Genetically engineered VSVs now have been generated by the laboratory and are being evaluated as a novel approach to cancer therapy. Dr. Barber is also interested in studying how viruses such as the human T cell lymphotropic virus (HTLV1), hepatitis C virus (HCV), 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 these processes could lead to an improvement of current treatments as well as generate new therapeutics and vaccines that may help eradicate infection and cancer.

Key Research

  • Understanding mechanisms of cellular host defense
  • Elucidating processes of cytosolic DNA signaling involving the cell protein STING
  • Analyzing the importance of STING in antiviral responses
  • Determining how STING influences inflammatory disease and cancer
  • Using oncolytic viruses to eliminate cancer cells exhibiting defective innate immunity

View published research articles by Dr. Barber in the NCBI PubMed