SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

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V I R A L O N C O L O G Y P R O G R A M V I R A L L Y M P H O M A 3) initiate clinical trials for AIDS-related malignancies in Brazil, and 4) study the molecular tumor pathogenesis of viral lymphomas in Africa and Brazil. Researchers in the Viral Oncology Program recently collaborated with Dr. Carlos Brites (Brazil) and successfully obtained funding through Fogarty to establish a viral oncology training program in Salvador, Brazil. Such studies are critical to understanding and developing rational therapy for malignancies in immunocompromised patients. The program recently was funded through the NCI for a study of inhibition of NF-κB and disruption of latency in high-grade primary lymphomas derived from Brazilian patients. Juan Carlos Ramos, M.D., (University of Miami) received a supplemental NCI grant linked to the AMC parent grant for a molecular study of PELs. In collaboration with the Federal University of Bahia in Brazil, a five-year training grant for AIDS/oncology was submitted. Bahia is a unique area that principally is populated by descendants of West Africa and is endemic for HTLV-I. The majority of non-Hodgkin’s lymphomas are associated with EBV or HTLV-I. Therefore, this presents an outstanding opportunity for clinical and basic investigation of these illnesses. Zambia is a central African nation located in the “AIDS and tumor belt.” In order to support their research activities in Zambia, the University of Nebraska at Lincoln, under Dr. Wood, and the University of Miami under Dr. Harrington and Charles D. Mitchell, M.D., have developed a successful training and research collaboration with the University of Zambia School of Medicine and the University Teaching Hospital, under the auspices of the Zambian Ministry of Health. This program, funded through the Fogarty International Post-Doctoral Training Program in HIV/ AIDS, has provided instruction to Zambian health care personnel in clinical, epidemiological, and basic science research methodology at both the Universities of Miami and Nebraska. UM/Sylvester Comprehensive Cancer Center Scientific Report 2004 133
V I R A L O N C O L O G Y P R O G R A M GLEN N. BARBER, PH.D. Professor of Microbiology and Immunology DESCRIPTION OF RESEARCH Dr. Barber’s research focuses on understanding the mechanisms of innate immunity to viral infection and malignant disease. Specifically, one area of research in his laboratory aims to understand the mechanisms by which the interferons (IFNs) mediate their anti-viral and anti-proliferative effects. One key IFN-inducible gene is the dsRNA-dependent protein kinase PKR, which is activated upon virus infection and limits viral replication by inhibiting host cell protein translation. Researchers recently have shown 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. They additionally have shown that PKR and IFN can contribute towards the induction of apoptosis in a virally infected cell. The laboratory currently is identifying new IFN-induced genes and examining their importance in cellular growth control and immunity. In addition to examining the mechanisms of innate immunity to viral infection, researchers in Dr. Barber’s laboratory are interested in studying how viruses such as hepatitis C (HCV) and human herpes virus type-8 (HHV-8) contribute towards oncogenesis. Such viruses are known to subvert key checkpoints of host-cell growth control. 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 PUBLICATIONS 2002 Fernandez, M, Porosnicu, M, Markovic, D, and Barber, GN. Genetically engineered vesicular stomatitis virus in gene therapy: application for treatment of malignant disease. Journal of Virology 76:895-904, 2002. Pataer, A, Vorburger, SA, Barber, GN, Chada, S, Mhashilkar, AM, Zou-Yang, H, Stewart, AL, Balachandran, S, Roth, JA, Hunt, KK, and Swisher, SG. Adenoviral transfer of the melanoma differentiation-associated gene 7 (mda7) induces apoptosis of lung cancer cells via upregulation of the double-stranded RNA-dependent protein kinase (PKR). Cancer Research 62:2239-43, 2002. Grandvaux, N, Servant, MJ, tenOever, B, Sen, GC, Balachandran, S, Barber, GN, Lin, R, and Hiscott, J. Transcriptional profiling of interferon regulatory factor 3 target genes: direct involvement in the regulation of interferon-stimulated genes. Journal of Virology 76:5532-9, 2002. Vorburger, SA, Pataer, A, Yoshida, K, Barber, GN, Xia, W, Chiao, P, Ellis, LM, Hung, MC, Swisher, SG, and Hunt, KK. Role for the doublestranded RNA activated protein kinase PKR in E2F-1-induced apoptosis. Oncogene 21:6278- 88, 2002. Ezelle, HJ, Markovic D, and Barber, GN. Generation of hepatitis C virus-like particles by use of a recombinant vesicular stomatitis virus vector. Journal of Virology 76:12325-34, 2002. 2003 Ogilvie, VC, Wilson, BJ, Nicol, SM, Morrice, NA, Saunders, LR, Barber, GN, and Fuller-Pace, FV. The highly related DEAD box RNA helicases p68 and p72 exist as heterodimers in cells. Nucleic Acids Research 31:1470-80, 2003. Saunders, LR and Barber, GN. The dsRNA binding protein family: critical roles, diverse cellular functions. The FASEB Journal 17:961-83, 2003. 134 UM/Sylvester Comprehensive Cancer Center Scientific Report 2004
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SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

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