Dr David J Hughes

Research Fellow

BMS 1.07B
tel. 01334 467197
fax.
djh25@st-andrews.ac.uk

Worldwide, viral infections represent major concerns to human health and global food security. From causing 15-20% of cancers to major outbreaks such as the Ebola epidemic in 2014, their effects are far-reaching. For most viruses, vaccines and targeted therapies are not available. Even if they were, many viruses rapidly mutate and develop resistance. Therefore, they represent major biomedical challenges.

Using a multidisciplinary approach, including molecular biology, cell biology and proteomics technologies, the objective of our research is to gain a deeper understanding of virus-host interactions at a fundamental level. In doing so, we may also uncover novel therapeutic targets. The primary rationale for studying drugable cellular processes that hinder virus biology is the potential to identify therapies that viruses find harder to develop resistance to.

A major focus of the lab is to gain insights into the fundamental role of posttranlational modifications such as acetylation and ubiquitin-like (Ubl) proteins (such as ubiquitin, NEDD8, ISG15 & SUMO) during viral infection.  As obligate intracellular pathogens, viruses are capable of rewiring cellular networks, and many have been shown to utilise these modification for their own benefit, or to antagonise their effects during the antiviral response. Therefore, a deeper understanding of their importance during viral infection may lead to the development of novel antiviral compounds. Indeed, we have recently shown NEDDylation is a viable target for the treatment of Kaposi's sarcoma-associated herpesvirus (KSHV) malignancies, such as primary effusion lymphoma (PEL). We study a number of viruses, including herpesviruses and paramyxoviruses.

 

Publications

Wood, J, Boyne, J, Paulus, C, Jackson, B, Nevels, MM, Whitehouse, A & Hughes, DJ 2016, 'ARID3B: a novel regulator of the Kaposi’s sarcoma-associated herpesvirus lytic cycle' Journal of Virology, vol 90, no. 20, pp. 9543-9555. DOI: 10.1128/JVI.03262-15
Leeming, GH, Kipar, A, Hughes, DJ, Bingle, L, Bennett, E, Moyo, NA, Tripp, RA, Bigley, AL, Bingle, CD, Sample, JT & Stewart, JP 2015, 'Gammaherpesvirus infection modulates the temporal and spatial expression of SCGB1A1 (CCSP) and BPIFA1 (SPLUNC1) in the respiratory tract' Laboratory Investigation, vol 95, pp. 610-624. DOI: 10.1038/labinvest.2014.162
Liu, L, Lear, Z, Hughes, DJ, Wu, W, Zhou, E-M, Whitehouse, A, Chen, H & Hiscox, JA 2015, 'Resolution of the cellular proteome of the nucleocapsid protein from a highly pathogenic isolate of porcine reproductive and respiratory syndrome virus identifies PARP-1 as a cellular target whose interaction is critical for virus biology' Veterinary Microbiology, vol 176, no. 1-2, pp. 109-119. DOI: 10.1016/j.vetmic.2014.11.023
Hughes, DJ, Wood, JJ, Jackson, BR, Baquero-Pérez, B & Whitehouse, A 2015, 'NEDDylation is essential for Kaposi’s Sarcoma-associated herpesvirus latency and lytic reactivation and represents a novel anti-KSHV target' PLoS Pathogens, vol 11, no. 3, e1004771. DOI: 10.1371/journal.ppat.1004771
Munday, DC, Wu, W, Smith, N, Fix, J, Noton, SL, Galloux, M, Touzelet, O, Armstrong, SD, Dawson, JM, Aljabr, W, Easton, AJ, Rameix-Welti, M-A, de Oliveira, AP, Simabuco, F, Ventura, AM, Hughes, DJ, Barr, JN, Fearns, R, Digard, P, Eléouët, J-F & Hiscox, JA 2015, 'Interactome analysis of the human respiratory syncytial virus RNA polymerase complex identifies protein chaperones as important co-factors that promote L protein stability and RNA synthesis' Journal of Virology, vol 89, no. 2, pp. 917-930. DOI: 10.1128/JVI.01783-14
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Dr David J Hughes Biomolecular Sciences Building
University of St Andrews
North Haugh
St Andrews
Fife
KY16 9ST
UK

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