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Research Interests: Understanding the molecular regulation and pathogenesis of the human herpesvirus, Epstein-Barr virus (EBV)

Research Description: Dr. Kenney’s research effort has been focused upon understanding the molecular regulation and pathogenesis of the human herpesvirus, Epstein-Barr virus (EBV).  Her work in EBV spans a broad range of topics, including viral gene regulation, the effects of the virus on the host immune response, and the development of novel, EBV-targeted therapies for EBV-positive tumors.  She has extensively studied the mechanisms by which both EBV immediate-early proteins, BZLF1 and BRLF1, activate the lytic form of viral infection.  Her group discovered that BZLF1 preferentially binds to, and transcriptionally activates, the methylated form of its downstream target promoter, suggesting a unique and unexpected mechanism by which EBV overcomes the inhibitory effect of viral genome methylation.   Her group has also shown how the two EBV immediate-early proteins alter the host cell environment in multiple different ways, including usurping control of the host cell cycle, activating a variety of signal transduction pathways, inhibiting p53 function, dispersing PML nuclear bodies, and attenuating the host innate immune response.  Dr. Kenney is now translating the results of these basic molecular studies into the development of new, EBV-targeted therapies for EBV-positive tumors. Her group is also developing a new small animal model to study EBV pathogenesis in vivo.

Selected recent publications

Bristol, J. A., Morrison, T. E., and Kenney, S. C.  CCAAT/Enhancer Binding Proteins α and β Regulate the Tumor Necrosis Factor Receptor 1 Gene Promoter.  Mol. Immunol., 46: 2706-2713, 2009.

Dickerson, S. J., Xing, Y., Robinson, A. R., Seaman, W. T., Gruffat, H., and Kenney, S. C.  Methylation-Dependent Binding of the Epstein-Barr Virus BZLF1 Protein to Viral Promoters.  PLoS Pathog., 5(3):e1000356, 2009.

Ryan, J. L., Jones, R. J., Elmore, S. H., Kenney, S. C., Miller, G., Schroeder, J. C., and Gulley, M. L.  Epstein-Barr Virus WZhet DNA Can Induce Lytic Replication in Epithelial Cells in Vitro, although WZhet Is Not Detectable in Many Human Tissues in Vivo.  Intervirology, 52:  8-16, 2009.

Bhende, P. M., Dickerson, S. J., Sun, X., Feng, W.-H., and Kenney, S. C.  X-Box-Binding Protein 1 Activates Lytic Epstein-Barr Virus Gene Expression in Combination with Protein Kinase D.  J. Virol., 81:  7363-7370, 2007.

Feng, W.-h., Kraus, R. J., Dickerson, S. J., Lim, H. J., Jones, R. J., Yu, X., Mertz, J. E., and Kenney, S. C.  ZEB1 and c-Jun Levels Contribute to the Establishment of Highly Lytic Epstein-Barr Virus Infection in Gastric AGS Cells.  J. Virol., 81: 10113-10122, 2007.

Jones, R. J., Dickerson, S., Bhende, P. M., Delecluse, H.-J., and Kenney, S. C.  Epstein-Barr Virus Lytic Infection Induces Retinoic Acid-responsive Genes through Induction of a Retinol-metabolizing Enzyme, DHRS9.  J. Biol. Chem., 282: 8317-8324, 2007.

Jones, R. J., Seaman, W. T., Feng, W.-H., Barlow, E., Dickerson, S., Delecluse, H.-J., and Kenney, S. C.  Roles of Lytic Viral Infection and IL-6 in Early Versus Late Passage Lymphoblastoid Cell Lines and EBV-associated Lymphoproliferative Disease.  Int. J. Cancer, 121:  1274-1281, 2007.

Yu, F., Feng, J., Harada, J. N., Chanda, S. K., Kenney, S. C., and Sun, R.  B Cell Terminal Differentiation Factor XBP-1 Induces Reactivation of Kaposi’s Sarcoma-associated Herpesvirus.  FEBS Lett., 581:  3485-3488, 2007.

Feng, W.-h., and Kenney, S. C.   Valproic Acid Enhances the Efficacy of Chemotherapy in EBV-Positive Tumors by Increasing Lytic Viral Gene Expression. Cancer Res., 66: 8762-8769, 2006.

González, C. M., Wong, E. L., Bowser, B. S., Hong, G. K., Kenney, S., and Damania, B. Identification and Characterization of the Orf49 Protein of Kaposi's Sarcoma-Associated Herpesvirus. J. Virol., 80: 3062-3070, 2006.

Bhende, P. M., Seaman, W. T., Delecluse, H.-J., and Kenney, S. C.   BZLF1 Activation of the Methylated Form of the BRLF1 Immediate-Early Promoter Is Regulated by BZLF1 Residue 186.  J. Virol., 79: 7338-7348, 2005.

Holley-Guthrie, E. A., Seaman, W. T., Bhende, P., Merchant, J. L., and Kenney, S. C. The Epstein-Barr Virus Protein BMRF1 Activates Gastrin Transcription.  J. Virol., 79: 745-755, 2005.

Hong, G. K., Gulley, M. L., Feng, W.-H., Delecluse, H.-J., Holley-Guthrie, E., and Kenney, S. C.   Epstein-Barr Virus Lytic Infection Contributes to Lymphoproliferative Disease in a SCID Mouse Model.  J. Virol., 79: 13993-14003, 2005.

Hong, G. K., Kumar, P., Wang, L., Damania, B., Gulley, M. L., Delecluse, H.-J., Polverini, P. J., and Kenney, S. C.   Epstein-Barr Virus Lytic Infection Is Required for Efficient Production of the Angiogenesis Factor Vascular Endothelial Growth Factor in Lymphoblastoid Cell Lines. J. Virol., 79: 13984-13992, 2005.

Israel, B. F., Gulley, M., Elmore, S., Ferrini, S., Feng, W.-h., and Kenney, S. C. Anti-CD70 Antibodies: A Potential Treatment for EBV⁺ CD70-Expressing Lymphomas.  Mol. Cancer Ther., 4: 2037-2044, 2005.

Bhende, P. M., Seaman, W. T., Delecluse, H.-J., and Kenney, S. C.   The EBV Lytic Switch Protein, Z, Preferentially Binds To and Activates the Methylated Viral Genome.  Nat. Genet., 36: 1099-1104, 2004.

Feng, W.-h., Cohen, J. I., Fischer, S., Li, L., Sneller, M., Goldbach-Mansky, R., Raab-Traub, N., Delecluse, H.-J., and Kenney, S. C. Reactivation of Latent Epstein-Barr Virus by Methotrexate: A Potential Contributor to Methotrexate-Associated Lymphomas. J. Natl. Cancer Inst., 96:1691-1702, 2004.

Feng W.-h., Hong, G., Delecluse, H.-J., and Kenney, S. C. Lytic Induction Therapy for Epstein-Barr Virus-Positive B-Cell Lymphomas. J. Virol., 78: 1893-1902, 2004.

Hong, G. K., Delecluse, H.-J., Gruffat, H., Morrison, T. E., Feng, W.-H., Sergeant, A., and Kenney, S. C. The BRRF1 Early Gene of Epstein-Barr Virus Encodes a Transcription Factor That Enhances Induction of Lytic Infection by BRLF1. J. Virol., 78: 4983-4992, 2004.

Li, Y., Webster-Cyriaque, J., Tomlinson, C. C., Yohe, M., and Kenney, S. Fatty Acid Synthase Expression Is Induced by the Epstein-Barr Virus Immediate-Early Protein BRLF1 and Is Required for Lytic Viral Gene Expression. J. Virol., 78: 4197-4206, 2004.

Morrison, T. E., Mauser, A., Klingelhutz, A., and Kenney, S. C. Epstein-Barr Virus Immediate-Early Protein BZLF1 Inhibits Tumor Necrosis Factor Alpha-Induced Signaling and Apoptosis by Downregulating Tumor Necrosis Factor Receptor 1. J. Virol., 78: 544-549, 2004.