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School of Medicine
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Gary S. Hayward
Department Affiliation: Primary: Oncology; Secondary: Pharmacology and Molecular Sciences; Pathology
Degree: Ph.D., University of Otago, New Zealand
Telephone Number: 410-955-8684
Fax Number: 410-955-8685
E-mail address: email@example.com
School of Medicine Address: Room 3M09, Cancer Research Building, 1650 Orleans Street, Baltimore, MD 21287
Pathways of human herpesvirus gene regulation, latency and pathogenesis; enhancer and silencer elements that modulate gene expression; mechanisms of positive and negative transcriptional regulation; interaction with and targeting to subnuclear domains by viral regulatory proteins; molecular piracy and promotion of angiogenesis by Kaposi's sarcoma herpesvirus; virus evasion of interferon-mediated innate immunity; virus evolution and virus hunting.
All human populations harbor latent inapparent infection with many or all of the eight known human herpesviruses. Both acute and chronic herpesvirus infections are particularly serious problems encountered clinically in immunosuppressed cancer and organ transplant patients, as well as in AIDS patients. However, they can also trigger a variety of tumors, lymphoproliferative and angiogenic diseases in immunocompetent patients. The focus of our laboratory research is aimed at understanding how the different classes of herpesviruses usurp control of transcription, DNA replication, cell cycle and other nuclear processes of their host cells and how they also block or evade apoptotic and immune responses in both the lytic and latent state. The large genomes (up to 200 genes) of the three representative herpesviruses that we study encode a series of well defined cascade-like pathways of gene expression that are switched on or off depending on appropriate activated or differentiated states of the host neuronal cells (HSV), myeloid precursor cells (CMV) or vascular endothelial cells (KSHV). Each pathway is driven by complex promoter enhancer domains that control expression of a set of key triggering nuclear IE transactivator proteins. In addition to acting as specific DNA-binding transcription factors that redirect certain cellular factors towards viral transcription, the IE lytic cycle trigger proteins carry out numerous functions associated with engaging histone acetylase and deacetylase complexes, altering PML nuclear bodies as well as UbE3L and SUMO modulated protein stability and degradation pathways, affecting chromatin structure and RNA nuclear shuttling, and blocking both interferon responses and cell cycle progression. In contrast, in the latent state, the viral lytic cycle triggers are repressed, the viral genomes are maintained as episomes and the cells may become immortalized. In addition, "captured" cellular genes encoded by KSHV and HCMV, including cytokines, chemokines and chemokine receptors have become modified by a process of "molecular piracy" to play key roles in viral pathogenesis. We ahve also used PCR sequencing-based virus hunting approaches to identify a novel genus of seven elephant herpesviruses that cause lethal hemorrhagic disease by infective vascular endothelial cells.
- Yu, Y., Wang, S.E., Hayward, G.S. The KSHV immediate-early transcription factor RTA encodes ubiquitin E3 ligase activity that targets IRF7 for proteosome-mediated degradation. Immunity. 22(1):59-70. 2005. Pub Med Reference
- Hayward, G.S. and Zong, J.-C. Modern evolutionary history of the human KSHV genome. Curr Top Microbiol Immunol. 312:1-42, 2006. Pub Med Reference
- Alcendor, D.J., Zong, J-C., Dolan, A., Gatherer, D., Davison, A.J. and Hayward, G.S. Patterns of divergence in the vCXCL and vGPCR gene clusters in primate cytomegalovirus genomes. Virology. 395:21-32, 2009. Pub Med Reference
- Yu, Y., Hayward, G.S. The ubiquitin E3 ligase RAUL negatively regulates type I interferon through ubiquitination of the transcription factors IRF7 and IRF3. Immunity 33(6):863-77, 2010. Pub Med Reference
- Latimer, E., Zong, J.C., Heaggans, S.Y., Richman, L.K., Hayward, G.S. Detection and evaluation of novel herpesviruses in routine and pathological samples from Asian and African elephants: Identification of two new probosciviruses (EEHV5 and EEHV6) and two new gammaherpesviruses (EGHV3B and EGHV5). Vet Microbiol. 147(1):28-41, 2011. Pub Med Reference
- Zachariah, A., Zong, J-C., Long, S.Y., Latimer, E.M., Heaggans, S.Y., Richman, L.K, Hayward, G.S. Fatal herpesvirus hemorrhagic disease in wild and orphan Asian elephants in southern India. J Wildl Dis. 49(2): 381-93, 2013. Pub Med Reference
Other graduate programs in which Dr. Hayward participates: