Dr. S. Diane Hayward
Herpesviruses and Tumorigenesis; Epstein-Barr Virus and HHV-8
Professor of Oncology
Professor of Pharmacology and Molecular Sciences Associate
Professor of Neurology
Ph.D., University of Otago, New Zealand
Fellow, Institute Gustave-Rousy, Dept. of Medicine, Paris, France
Fellow, Dept. of Molecular Genetics, University of Heidelburg, Heidelburg, Germany
Herpesvirus-Host Cell Interactions
Epstein-Barr virus (EBV) and Kaposi’s sarcoma associated herpesvirus (KSHV) are human herpesviruses that are associated with a variety of malignancies. We seek to understand the genesis of virus-associated cancers by examining the mechanism of action of virus proteins that interact with cell signaling pathways to promote cell proliferation and cell survival. The laboratory also examines the regulation of lytic EBV and KSHV replication. Lytic replication is necessary for virus spread to new hosts and unregulated virus replication is a risk factor for the development of EBV and KSHV associated cancers. In collaboration with the Zhu laboratory we are developing herpesvirus proteomic arrays as new tools for probing virus-cell interactions. The protein arrays are being used to identify post-translational modifications such as phosphorylation and sumolation that modify virus protein functions. The ability of viral kinases to modify host protein functions is also being investigated using human protein arrays to identify viral kinase substrates.
Shamay M., Krithivas A., Zhang J. and Hayward S.D.: Recruitment of the de novo DNA methyltransferase Dnmt3a by Kaposi's sarcoma-associated herpesvirus LANA. Proc. Natl. Acad. Sci. USA 103: 14554-9, 2006.
Martin H.J., Lee J.M., Walls D. and Hayward S.D.: Manipulation of the toll-like receptor 7 signaling pathway by Epstein-Barr virus. J. Virol. 81: 9748-58, 2007.
Liu J., Martin H.J., Liao G. and Hayward S.D.: The Kaposi's sarcoma-associated herpesvirus LANA protein stabilizes and activates c-Myc. J. Virol. 81: 10451-9, 2007.
Lo A.K., To K.F., Lo K.W., Lung R.W., Hui J.W., Liao G. and Hayward S.D.: Modulation of LMP1 protein expression by EBV-encoded microRNAs. Proc. Natl. Acad. Sci. USA 104: 16164-9, 2007.
Zhu J., Liao G., Shan L., Zhang J., Chen M.R., Hayward G.S., Hayward S.D., Desai P. and Zhu H.: Protein array identification of substrates of the Epstein-Barr virus protein kinase BGLF4. J. Virol. 83: 5219-31, 2009. PMCID: 2682057
Shamay M., Greenway M., Liao G., Ambinder R.F. and Hayward S.D.: De novo DNA methyltransferase DNMT3b interacts with NEDD8-modified proteins. J. Biol. Chem. 285: 36377-86, 2010. PMCID: 2978566
Zheng, D., Wan, J., Cho, Y.G., Wang, L., Chiou, C.-J., Pai, S., Woodard, C., Zhu, J., Liao, G., Martinez-Maza, O., Qian, J., Zhu, H., Hayward, G.S., Ambinder, R.F., and Hayward, S.D. Comparison of Humoral Immune Responses to Epstein-Barr Virus and Kaposi's Sarcoma Associated Herpesvirus Using a Viral Proteome Microarray. J. Infect. Dis. in press, 2011.
Li, R., Zhu, J., Xie, Z., Liao, G., Liu, J., Chen, M.-R., Hu, S., Woodard, C., Lin, J., Taverna, S., Desai, P., Ambinder, R.F., Hayward, G.S., Qian, J., Zhu, H. and Hayward, S.D.: Conserved Herpesvirus Kinases Regulate TIP60 to Promote Virus Replication. Cell Host & Microbe in press, 2011.