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School of Medicine
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Gary S. Hayward, Ph.D.
Professor of Oncology
Research Interests: Virus evolution and virus hunting; Virus evasion of interferon-mediated innate immunity; Molecular piracy and promotion of angiogenesis by Kaposi's sarcoma herpesvirus; Interaction with and targeting to subnuclear domains by viral regulatory proteins; Mechanisms of positive and negative transcriptional regulation; Enhancer and silencer elements that modulate gene expression; Latency and pathogenesis; Pathways of human herpesvirus gene regulation ...read more
- Professor of Oncology
- Professor of Pathology
- Professor of Pharmacology and Molecular Sciences
Centers & Institutes
Research & Publications
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 have 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.
Lab Website: Gary S. Hayward Laboratory
Selected PublicationsView all on Pubmed
Ehrlich ES, Chmura JC, Smith JC, Kalu NN, Hayward GS. KSHV RTA abolishes NFκB responsive gene expression during lytic reactivation by targeting vFLIP for degradation via the proteasome. PLoS One. 2014 Mar 10;9(3):e91359. doi: 10.1371/journal.pone.0091359. eCollection 2014. PMID: 24614587 [PubMed - in process]
Ling PD, Reid JG, Qin X, Muzny DM, Gibbs R, Petrosino J, Peng R, Zong JC, Heaggans SY, Hayward GS. Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 1A. Genome Announc. 2013 Apr 11;1(2):e0010613. doi: 10.1128/genomeA.00106-13. PMID: 23580705
Zachariah A, Zong JC, Long SY, Latimer EM, Heaggans SY, Richman LK, Hayward GS. Fatal herpesvirus hemorrhagic disease in wild and orphan asian elephants in southern India. J Wildl Dis. 2013 Apr;49(2):381-93. doi: 10.7589/2012-07-193. PMID: 23568914
Atkins L, Zong JC, Tan J, Mejia A, Heaggans SY, Nofs SA, Stanton JJ, Flanagan JP, Howard L, Latimer E, Stevens MR, Hoffman DS, Hayward GS, Ling PD. Elephant endotheliotropic herpesvirus 5, a newly recognized elephant herpesvirus associated with clinical and subclinical infections in captive Asian elephants (Elephas maximus). J Zoo Wildl Med. 2013 Mar;44(1):136-43. PMID: 23505714
Stanton JJ, Zong JC, Eng C, Howard L, Flanagan J, Stevens M, Schmitt D, Wiedner E, Graham D, Junge RE, Weber MA, Fischer M, Mejia A, Tan J, Latimer E, Herron A, Hayward GS, Ling PD. Kinetics of viral loads and genotypic analysis of elephant endotheliotropic herpesvirus-1 infection in captive Asian elephants (Elephas maximus). J Zoo Wildl Med. 2013 Mar;44(1):42-54. PMID: 23505702