My research group studies various aspects of adenovirus cell and molecular biology. Our current research aims are:
- to understand the interactions of adenovirus with its host cell at the molecular level, particularly the innate responses of the cell to infection
- to gain insight into the relationship between cellular stress responses and infection
- to understand how adenovirus late gene expression is controlled in productive infections and reactivation from latency in lymphoid cells
- to use our knowledge of adenoviruses to generated improved adenovirus vectors for gene therapy and recombinant vaccine delivery
More detailed descriptions of our work are available on my Research Page.
or, for a explanation of our work without the detail and jargon, view my Research for a General Audience page.
View a list of my older publications (pdf)
After gaining my first degree in Biochemistry from Oxford, U.K., I began my research career studying for a PhD with Dr Lionel Crawford, working in the labs of what was then the Imperial Cancer Research Fund (now Cancer Research UK) at Lincolns Inn Fields, London. This work focused on the then newly discovered cellular tumour suppressor protein, p53, which was being studied in the context of SV40 infection. From there I moved to a postdoctoral position with Prof Tom Shenk, first at SUNY Stony Brook and then at Princeton. There I learned the adenovirus genetic system that I have worked on ever since. I left Princeton in 1988 to take up a lectureship in the Department of Biological Sciences, University of Warwick, where I am now Professor.
I have a broad interest in adenovirus molecular and cell biology and my work has made several major contributions to this field. A particular focus has been the functions of the proteins encoded by the viral E1B and E4 genes, and most recently the L4 gene, in controlling viral gene expression and the biology of the host cell. My studies of E4 proteins have led me into a exploring the diversity and function of host cell PML proteins. These proteins are crucial in many aspects of cell function, particularly the innate immune response. A further significant strand of recent work has been in the development of adenovirus as a vector for gene delivery.
I have co-authored a successful undergraduate textbook, Introduction to Modern Virology, with Prof. Nigel Dimmock and Prof. Andrew Easton.
- Donovan-Banfield, I'ah, Turnell, Andrew S., Hiscox, Julian A., Leppard, Keith, Matthews, David A., 2020. Deep splicing plasticity of the human adenovirus type 5 transcriptome drives virus evolution. Communications Biology, 3
- Møller-Olsen, Christian, Ross, Toby, Leppard, Keith, Foisor, Veronica, Smith, Corinne J., Grammatopoulos, Dimitris, Sagona, Antonia P., 2020. Bacteriophage K1F targets Escherichia coli K1 in cerebral endothelial cells and influences the barrier function. Scientific Reports, 10
- Windheim, Mark, Höning, Stefan, Leppard, Keith, Butler, Larrisa, Seed, Christina, Ponnambalam, Sreenivasan, Burgert, Hans-Gerhard, 2016. Sorting motifs in the cytoplasmic tail of the immunomodulatory E3/49K protein of species D adenoviruses modulate cell surface expression and ectodomain shedding. Journal of Biological Chemistry, 291, pp. 6796-6812
- Atwan, Zeenah, Wright, Jordan L., Leppard, Keith, Woodman, Andrew, 2016. Promyelocytic leukemia protein isoform II inhibits infection by human adenovirus type 5 through effects on HSP70 and the interferon response. Journal of General Virology, 97, pp. 1955-1967
- Bridges, Rebecca G., Sohn, Sook-Young, Wright, Jordan L., Leppard, Keith, Hearing, Patrick, 2016. The adenovirus E4-ORF3 protein stimulates SUMOylation of general transcription factor TFII-I to direct proteasomal degradation. mBio, 7 (1)
- Wright, Jordan L., Atwan, Zeenah, Morris, S. J. (Susan J.), Leppard, Keith, 2015. The human adenovirus type 5 L4 promoter is negatively regulated by TFII-I and by L4-33K. Journal of Virology, 89 (14), pp. 1-36
- Chen, Yixiang, Wright, Jordan L., Meng, Xueqiong, Leppard, Keith, 2015. Promyelocytic leukemia protein isoform II promotes transcription factor recruitment to activate interferon ß and interferon-responsive gene expression. Molecular and Cellular Biology, 35 (10), pp. 1660-1672
- Maunder, Helen E., Taylor, Geraldine, Leppard, Keith, Easton, A. J. (Andrew J.), 2015. Intranasal immunisation with recombinant adenovirus vaccines protects against a lethal 2 challenge with pneumonia virus of mice. Vaccine, 33 (48), pp. 6641-6649
- Wright, Jordan, Leppard, Keith, 2013. The human adenovirus 5 L4 promoter is activated by cellular stress response protein p53. Journal of Virology, 87 (21), pp. 11617-11625
- Morris, S. J. (Susan J.), Scott, Gillian E., Leppard, Keith, 2010. Adenovirus late phase infection is controlled by a novel L4 promoter. Journal of Virology, Vol.84 (No.14), pp. 7096-7104
- Morris, S. J. (Susan J.), Farley, Daniel C., Leppard, Keith, 2010. Generation of cell lines to complement Adenovirus vectors using recombination-mediated cassette exchange. BioMed Central Ltd, Vol.10 (No.92)
- Morris, S. J. (Susan J.), Leppard, Keith, 2009. Adenovirus serotype 5 L4-22K and L4-33K proteins have distinct functions in regulating late gene expression. Journal of Virology, Vol.83 (No.7), pp. 3049-3058
- Leppard, Keith, Emmott, Edward, Cortese, Marc S., Rich, Tina, 2009. Adenovirus type 5 E4 Orf3 protein targets promyelocytic leukaemia (PML) protein nuclear domains for disruption via a sequence in PML isoform II that is predicted as a protein interaction site by bioinformatic analysis. Journal of General Virology, Vol.90 (No.1), pp. 95-104
- Hoppe, Anne, Beech, Stephanie J., Dimmock, John, Leppard, Keith, 2006. Interaction of the adenovirus type 5 E4 Orf3 protein with promyelocytic leukemia protein isoform II is required for ND10 disruption. Journal of Virology, Vol.80 (No.6), pp. 3042-3049
- Leppard, Keith, Wright, J.. Targeting of PML Proteins and PML Nuclear Bodies by DNA Tumour Viruses. In Gaston , K. (ed.), The Small DNA Tumour Viruses, United Kingdom, Caister Academic Press, pp. 257-282
- Leppard, Keith, 2014. Adenoviruses : molecular biology. Caplan, Michael J. (ed.), Reference Module in Biomedical Sciences, Elsevier Inc
- Leppard, Keith, 2008. Adenoviruses: Molecular Biology. In Mahy, Brian W. J.; Van Regenmortel, Marc H. V. (eds.), Encyclopedia of Virology, Amsterdam ; London, Elsevier Ltd, pp. 17-23
- Easton, A. J. (Andrew J.), Leppard, Keith, 2014. Experimental drugs were used for HIV, but Ebola is a riskier bet. The Conversation Trust (UK)
|Title||Funder||Award start||Award end|
|Defining and exploiting the role of PML protein in innate immune responses to pathogens - MRC Research Grant||MRC||01 Aug 2017||30 Jun 2021|
|Understanding and re-engineering adenovirus late gene expression: controlling the gatekeeper to productive infection||Wellcome Trust||01 Jun 2011||18 Dec 2014|
|Comparison of the adenovirus early to late transition in epithelial and lymphoid cells||Society for General Microbiology||28 Jul 2014||15 Sep 2014|
|Evaluating the gene delivery potential E1, L4 - deficient adenovirus vectors,||BBSRC||16 Jan 2007||15 Jan 2010|
|Generation and Characterisation of L4 - Deleted Adenovirus||Society for General Microbiology||29 Jun 2009||02 Oct 2009|
|Development of Novel Complementation Systems for Highly Deleted Adenovirus Vectors||BBSRC||01 Feb 2004||28 Feb 2007|