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Glen N. Barber, Ph.D.,

Professor, Division of Hematology/Oncology
Associate Director of Basic Science for SCCC

tel: 305-243-5914
fax: 305-243-5885

Mailing Address
P.O. Box 016960- Rm 511, (M-877)
Miami, FL 33101

For Patients

Practice Locations
Papanicolaou Building

Languages Spoken
English

Education

CAMR, London University
London, United Kingdom Ph.D. Molecular Virology 1988

University of Portsmouth
Hampshire, United Kingdom B.A. Molecular Biology/Biophysics 1984

Dr. Glen Barber, Ph.D., joined UM in 1999, having served as an Assistant Professor in the Department of Microbiology and Immunology at Emory University School of Medicine, Atlanta, Georgia. He has played an important role in development of graduate courses in his Department of Microbiology and Immunology at the University of Miami, where he is Associate Professor. Dr. Barber is also co-leader of the UMSCCC Viral Oncology Program. He is very well funded and has an impressive publication record. Moreover, he has considerable experience in mentoring post-doctoral and post-MD fellows and graduate students.

Research Interests

Dr. Barber's laboratory is developing novel virus-based therapies for breast and other cancers and his research has contributed key insights into mechanisms of innate immunity to viral infection and malignant disease. The laboratory focuses understanding the mechanisms by which the interferons (IFNs) mediate their anti-viral and anti-proliferative effects. One key IFN-inducible gene, the dsRNA-dependent protein kinase PKR, is activated upon virus infection and limits viral replication by inhibiting host cell protein translation. Dr Barber recently showed that mice lacking PKR are very sensitive to lethal infection by vesicular stomatitis virus (VSV) and influenza virus, underscoring the importance of this molecule in host defense. Current research is directed to identifying new IFN-induced genes and examining their importance in cellular growth control and immunity and dysregulation in cancer cells. Dr. Barber's lab also investigates how hepatitis C virus, Epstein-Barr virus and HHV8 contribute to oncogenesis. Understanding mechanisms involved in these processes could lead to an improvement of current therapies, as well as the identification of new therapeutic targets in malignant disease involving these viruses. Dr. Barber has developed VSV-based viral vectors that carry apoptosis-inducing cDNAs and preferentially kill infected cancer cells due to the selective growth properties of VSV in cancer versus normal cells. A variety of applications of these oncolytic VSV vectors are being developed to allow use of this technology in cancer gene therapy.

Laboratory Interests

Our laboratory is interested in understanding mechanisms of innate immunity to viral infection and malignant disease. Gaining insight into mechanisms of the innate immune process affords the opportunity of developing translational research programs involving the design of novel vaccines and therapeutics, to combat disease.

Innate Immunity: Activation of innate immune responses galvanizes early host defense mechanisms as well as invigorates adaptive immune responses involving cytotoxic T cell activity and antibody production. The recognition of pathogenic microbes and the triggering of the innate immune cascade has become the subject of intense research over the past few years. Particular attention has recently focused on the role of the Toll-like receptors (TLRs), which have emerged as key cell surface molecules responsible for recognizing conserved components of pathogenic microorganisms (referred to as pathogen associated molecular patterns -PAMPs). The TLRs were first identified in Drosophila and have been shown to play an important role in development as well as in host defense against fungi and bacteria. In mammalian cells, there appear to be at least 11 TLR members, each of which respond to different PAMPs such as extracellular lipopolysaccharide (TLR 4) and dsRNA (TLR3). Following ligand binding, signaling pathways are initiated that triggers the transcriptional stimulation of numerous genes such as the type I IFN's, that induce antiviral responses, as well as other genes that facilitate the innate and adaptive immune responses.

A second, TLR-independent, intracellular, viral/dsRNA recognition pathway involving the retinoic acid inducible gene I (RIG-I) has recently been reported. RIG-I and homolog melanoma differentiation antigen 5 (MDA5) are helicases that also activate type I IFN following interaction with viral dsRNA. We have recently shown that efficient virus/dsRNA-intracellular signaling of type I IFN also requires ‘death domain' containing proteins such as receptor interacting protein 1 (RIP1) and the Fas-associated death domain molecule (FADD). Our ongoing research program includes further understanding the mechanisms of viral-mediated innate immune signaling in the cell.

These studies include analyzing the function of the inteferon's (IFN's). The IFNs are induced by Toll dependent and independent pathways, act by being secreted from the cell and following interaction with specific receptors, mediate their action by inducing the expression of numerous genes. IFN-inducible genes important for antiviral host defense still remain to be fully identified and characterized, but one such critical gene is referred to as PKR, for protein kinase RNA-dependent. PKR is activated following interaction with viral dsRNA, an event that eventually causes the inhibition of viral protein synthesis in the cell. We have shown that mice lacking PKR are very sensitive to virus infection, underscoring the importance of this molecule in host defense. Given this, part of our research goals includes studying the regulation of translation initiation, and its role in tumor biology and innate immunity. We are also interested in identifying new IFN-induced genes and examining their importance in antiviral and antiproliferative activity, as well as identifying new regulators and substrates of PKR such as the NFAR's (Nuclear Factors Associated with dsRNA) proteins.

Cancer Virotherapy: Recent data from our laboratory has also shown that vesicular stomatitis virus, VSV, a relatively non-pathogenic, RNA virus, can selectively induce the killing of malignant cells, but not normal cells. VSV appears able to kill transformed cells since these hosts exhibit the hallmarks of a flawed innate immune system which is essential for preventing VSV replication. The simple genetic constitution of VSV, lack of any known transforming properties, extensive knowledge relating to its interaction with the immune system and the ability to genetically manipulate the organism affords an ideal opportunity to exploit the oncolytic potential of this virus. Thus, aside from preferentially replicating in malignant cells and exerting direct antitumor activity, VSV recombinants are being generated that could increase a tumors susceptibility to chemotherapeutic agents and/ or the host immune response. Our data demonstrates that VSV could provide a promising approach to cancer therapy.

Viral Oncology: Certain viruses are considered the second most important cause of cancer in humans, contributing up to 20% of all cancers worldwide. Human cancers associated with virus infection include cervical cancer and head and neck cancer (HPV infection), adult T-cell leukemia (ATL- HTLV-1 infection), hepatocellular carcinoma (HCC – HCV or HBV infection), non-hodgkins lymphoma (EBV infection) and kaposi's sarcoma (HHV8 infection). Since viruses are foreign agents, they make excellent targets for vaccination and therapeutic intervention. They also make excellent models for developing novel immunotherapeutic strategies. Based on our understanding of innate immune responses, we are developing translational research programs that target the prevention or treatment of viral associated malignant disease.

By understanding basic mechanisms of host defense responses to viral infection and malignant disease we hope to understand the causes of disease and potentially develop new treatment for the prevention of viral and malignant disease.

Publications

List of publications by Glen N. Barber, Ph.D.,

CAMR, London University London, United Kingdom	Ph.D.	Molecular Virology	1988
University of Portsmouth Hampshire, United Kingdom	B.A.	Molecular Biology/Biophysics	1984