- 2007- present Director, Biomedical Research Centre, University of East Anglia
- 1997-2005 Head of Department of Immunology and Pathology, Institute for Animal Health, Pirbright Laboratory, Woking, Surrey.
- 1994-1997 Head, Virus Cell Biology Group, Institute for Animal Health, Pirbright Laboratory, Woking, Surrey.
- 1991-1996 Assistant Professor, Department of Medicine, Harvard Medical School, Boston USA.
- 1991 - 1994 Assistant Professor, Division of Immunology, Beth Israel Hospital, Harvard Medical School, Boston, MA.
- 1988-1992 Claudia Adam's Barr Investigator in Cancer Research, Fellow of the Medical Foundation of the Charles King Trust and Basil O'Connor Scholar Award of the March of Dimes Research Foundation, Dept Molecular Immunology, Dana Farber Cancer Institute, Harvard Medical School
- 1982-1988 BBSRC NATO Fellow and Fellow of the Parker Francis Pulmonary Research Foundation. Department of Cell Biology, Washington University Medical School, St Louis.
- 1976 B.Pharm. London University
- 1980 Ph.D. Liverpool Moore’s University
Key Research Interests
Autophagy is a membrane trafficking pathway that generates autophagosomes which deliver cytosol to lysosomes for degradation. Autophagy provides a powerful means of removing intracellular pathogens and is an important arm of innate immunity to infection. We are interested in understanding how autophagy is activated during virus infection and determining the effects of autophagy on the outcome of disease. We study the role played by specific viral proteins in activating autophagy in cells, and have generated mouse models to study the role played by autophagy in controlling viral infection of specific tissues ‘in vivo’.
Recent genome wide association screens have identified autophagy gene Atg16L1 as a risk allele for Crohn’s disease, an inflammatory disease of the bowel. Susceptibility to Crohn’s disease is also linked to mutations in NOD2, a microbial sensor that activates autophagy during infections. We are investigating whether the inflammation seen in Crohn’s disease is caused by defects in the control of microorganisms by autophagy in gut epithelial cells.
Many human diseases are caused by defective genes and there is great interest in developing gene therapy vectors to replace genes associated with specific illnesses. Many gene therapy vectors are based on viruses and cationic polymers. We are interested in understanding how autophagy pathways respond to these vectors and whether they slow gene delivery into cells.
Roberts, R, Al-Jamal, Whelband, M, Thomas, P, Jefferson, M, van den Bossche, Powell, P, Kostarelos, K and Wileman, T (2013) Autophagy and formation of tubulovesicular autophagosomes provide a barrier against nonviral gene delivery. Autophagy, 9 :667-682.
Zhigang, Z., Mogensen, Mette M., Powell, P. P., Curry, S. and Wileman, Thomas (2013) Foot-and-Mouth Disease virus 3Cpro induces fragmentation of the Golgi and blocks intra-Golgi transport. Journal of Virology. ISSN 0022-538X (In Press)
Meyer HJ. Cottam E. Wileman T and Britton P (2013) Visualising the autophagy pathway in avian cells and its application to studying Infectious Bronchitis Virus. Autophagy 9:496-509
Berryman S., Brooks E., Burman A., Hawes P., Roberts R., Netherton C., Monaghan P., Whelband M., Cottam M, Elazar Z., Jackson T and T. Wileman (2012) Foot-and-mouth disease virus activates autophagy and generates autophagosomes independently of replication and class III phosphoinositide-3 kinase. J. Virol 86:12940-12953
Cottam, EM, Maier HJ, Manifava M, Vaux LC, Schoenfelder P, Gerner W, Paul Britton P,
Ktistakis NT and Wileman T (2011) Coronavirus nsp6 proteins generate autophagosomes from the endoplasmic reticulum via an omegasome intermediate. Autophagy 7:1-13
Windsor, M, Hawes, P, Monaghan, P, Snapp, E, Salas, ML, Rodriguez, JM and Wileman, T (2012) Mechanism of collapse of endoplasmic reticulum cisternae during African swine fever virus infection. Traffic, 13. pp. 30-42.
Stappenbeck, TS., Rioux, JD., Mizoguchi, A, Saitoh, T, Huett, A, Darfeuille-Michaud, A, Wileman, T, Mizushima, N, Carding, S, Akira, S, Parkes, M and Xavier, R J. (2011) Crohn disease: A current perspective on genetics, autophagy and immunity. Autophagy, 7 :355-374. ISSN 1554-8627
Wileman, TE (2007) Aggresomes and pericentriolar sites of virus assembly. Cellular defense or viral design? Ann Rev Microbiol, 61 (1). pp. 149-167.
Wileman, TE (2006) Aggresomes and autophagy generate sites for virus replication
Bensaude, E., Turner, J. L., Wakeley, P. R., Sweetman, D. A., Pardieu, C., Drew, T. W., Wileman, T., Powell, P. P. 2004, 'Classical swine fever virus induces proinflammatory cytokines and tissue factor expression and inhibits apoptosis and interferon synthesis during the establishment of long-term infection of porcine vascular endothelial cells', J Gen Virol, vol. 85, no. Pt 4, pp. 1029-37.
Brazzoli, M, Crotta, S, Bianchi, A, Bagnoli, F, Monaghan, P, Wileman, T, Abrignani, S, Merola, M 2007, 'Intra cellular accumulation of hepatitis C virus proteins in a human hepatoma cell line', Journal of Hepatology, vol. 46, pp. 53-59.
Cobbold, C, Windsor, M, Parsley, J, Baldwin, B, Wileman, T 2007, 'The reduced redox potential of the cytosol is important for African swine Fever virus capsid assembly and maturation', J Gen Virol, vol. 86, pp. 687-696.
Cobbold, C, Windsor, M, Wileman, T 2001, 'A virally encoded chaperone specialised for folding of the major capsid protein of African swine fever virus', Journal of Virology, vol. 75, no. 16, pp. 7221-7229.
Denyer, M. S., Wileman, T. E., Stirling, C. M., Zuber, B., Takamatsu, H. H. 2006, 'Perforin expression can define CD8 positive lymphocyte subsets in pigs allowing phenotypic and functional analysis of natural killer, cytotoxic T, natural killer T and MHC un-restricted cytotoxic T-cells', Vet Immunol Immunopathol, vol. 110, no. 3-4, pp. 279-92.
Garner, W, Denyer, M S, Takamatsu, H-H, Wileman, T, Wiesmuller, K-H, Pfaff, E, Saalmuller, A 2006, 'Identificastion of novel foot and mouth disease virus specific T-cell epitopes in c/c and d/d haplotype miniature swine', Virus Research, vol. 121, pp. 223-228.
Heath, C. M., Windsor, M., Wileman, T. 2003, 'Membrane association facilitates the correct processing of pp220 during production of the major matrix proteins of African swine fever virus', J Virol, vol. 77, no. 3, pp. 1682-90.
Heath, C.M., Heath, C.M., Windsor, M, Wileman, T 2001, 'Aggresomes Resemble Sites Specialized for Virus Assembly.', Journal of Cell Biology, vol. 153, no. 3, pp. 449.
Jouvenet, N., Monaghan, P., Way, M., Wileman, T. 2004, 'Transport of African swine fever virus from assembly sites to the plasma membrane is dependent on microtubules and conventional kinesin', J Virol, vol. 78, no. 15, pp. 7990-8001.
Jouvenet, N., Wileman, T. 2005, 'African swine fever virus infection disrupts centrosome assembly and function', J Gen Virol, vol. 86, no. Pt 3, pp. 589-94.< /p>
Jouvenet, N., Windsor, M, Rietdorf, J, Hawes, P, Monaghan, P, Way, M, Wileman, T 2006, 'African Swine Fever virus induces filopodia-like projections at the plasma membrane', Cellular Microbiology,
Jouvenet, N., Windsor, M, Rietdorf, J, Hawes, P, Monaghan, P, Way, M, Wileman, T In press 2006, 'African Swine Fever virus induces filopodia-like projections at the plasma membrane', Cellular Microbiology,
Knox, C., Moffat, K., Ali, S., Ryan, M., Wileman, T. 2005, 'Foot-and-mouth disease virus replication sites form next to the nucleus and close to the Golgi apparatus, but exclude marker proteins associated with host membrane compartments', J Gen Virol, vol. 86, no. Pt 3, pp. 687-96.
La Rocca, S. A., Herbert, R. J., Crooke, H., Drew, T. W., Wileman, T. E., Powell, P. P. 2005, 'Loss of interferon regulatory factor 3 in cells infected with classical swine fever virus involves the N-terminal protease, Npro', J Virol, vol. 79, no. 11, pp. 7239-47.
McCrossan, M, Windsor, M, Ponnambalam,S, Armstrong, J, Wileman, T 2001, 'The trans Golgi network is lost from cells with African swine fever virus', Journal of Virology, vol. 75, no. 23, pp. 11755-11765.
Moffat, K., Howell, G., Knox, C., Belsham, G. J., Monaghan, P., Ryan, M. D., Wileman, T. 2005, 'Effects of foot-and-mouth disease virus nonstructural proteins on the structure and function of the early secretory pathway: 2BC but not 3A blocks endoplasmic reticulum-to-Golgi transport', J Virol, vol. 79, no. 7, pp. 4382-95.
Moffat, K., Knox, C., Howell, G., Clark, S J, Yang, H., Graham, J B, Ryan, M., Wileman, T 2007, 'Inhibition of the Secretory Pathway by Foot-and-Mouth Disease Virus 2BC Protein Is Reproduced by Coexpression of 2B and 2C, and the Site of Inhibition Is Determined by the Subcellular Location of 2C', Journal of Virology, vol. 81, no. 3, pp. 1129-1139.
Netherton, C. L, McCrossan, M, Denyer, M, Ponnambalam, S, Armstrong, J, Takamatsu, H-H, Wileman, T In press, 'African swine Fever virus causes microtubule dependent dispersal of the trans-Golgi network and slows delivery of membrane proteins including MHC class 1 to the plasma membrane', J. Virol,
Netherton, C. L, McCrossan, M, Denyer, M, Ponnambalam, S, Armstrong, J, Takamatsu, H-H, Wileman, T 2006, 'African swine Fever virus causes microtubule dependent dispersal of the trans-Golgi network and slows delivery of membrane proteins including MHC class 1 to the plasma membrane', J. Virol, vol. 80, no. 22, pp. 11385-11392.
Netherton, C. L., Parsley, J. C., Wileman, T. 2004, 'African swine fever virus inhibits induction of the stress-induced proapoptotic transcription factor CHOP/GADD153', J Virol, vol. 78, no. 19, pp. 10825-8.
Netherton, C., Moffat, K., Brooks, L, Wileman, T In press, 'Cellular compartments used for virus replication', Adv Virus Res,
Netherton, C., Rouiller, I., Wileman, T. 2004, 'The subcellular distribution of multigene family 110 proteins of African swine fever virus is determined by differences in C-terminal KDEL endoplasmic reticulum retention motifs', J Virol, vol. 78, no. 7, pp. 3710-21.
Sambrook, J G, Sehra, H, Coggill, P, Humphrey, S, Palmer, S.R, Sims, S, Takamatsu, H-H, Wileman, T, Archibald, A L, Beck, S 2006, 'Identification of a single Killer Immunoglobulin-like Receptor (KIR) gene in the porcine Leukocyte Receptor Complex on pig chromosome 6q.', Immunogenetics, vol. 58, pp. 481-486.
Stefanovic, S., Windsor, M., Nagata, K. I., Inagaki, M., Wileman, T. 2005, 'Vimentin rearrangement during African swine fever virus infection involves retrograde transport along microtubules and phosphorylation of vimentin by calcium calmodulin kinase II', J Virol, vol. 79, no. 18, pp. 11766-75.
Stirling, C. M., Charleston, B., Takamatsu, H., Claypool, S., Lencer, W., Blumberg, R. S., Wileman, T. E. 2005, 'Characterization of the porcine neonatal Fc receptor--potential use for trans-epithelial protein delivery', Immunology, vol. 114, no. 4, pp. 542-53.
Takamatsu, H-H, Denyer, M S, Stirling, C, Cox, S, Aggarwal, N, Dash, P, Wileman, T, Barnett, P V 2006, 'Porcine gd T-cells: Possible roles on the innate and adaptive immune responses following virus infection', Vet Immunol Immunopathol, vol. 112, pp. 49-61.
Wileman, T, A European Perspective on the coming Global Challengein Annual International Conference of the Global Society of Researchers in Assessment Methodologies2001.
Wileman, T, 'Aggresomes and pericentrioloar sites of virus assembly. Cellular defence or viral design?', Ann Rev Microbiol,
Wileman, T. 2006, 'Aggresomes and autophagy generate sites for virus replication', Science, vol. 312, no. 5775, pp. 875-8.
Yang, H., Parkhouse, R. M., Wileman, T. 2005, 'Monoclonal antibodies that identify the CD3 molecules expressed specifically at the surface of porcine gammadelta-T cells', Immunology, vol. 115, no. 2, pp. 189-96.
Teaching interests focus on the cellular microbiology of infection by pathogens. This emphasises that an understanding of basic cell biology and immunology allows us to explain complex processes such as virulence, pathogenesis and understand how pathogens maintain persistent infections. The same themes underpin the design of anti viral therapies such as anti-viral drugs and vaccines.
Lectures on virus pathogenesis and anti-viral agents
Unit Lead for Unit 6, Endocrinology
External Activities and Indicators of Esteem
- 1989 - 1992 Basil O’Connor Scholar Award, March of Dimes, USA
- 1989 - 1992 Basil O’Connor Scholar Award, March of Dimes, USA
- 1988 - 1989 Claudia Adams Barr Innovative Cancer Research Award, USA
- 1985 - 1988 Parker B. Francis Pulmonary Research Fellowship, USA
- 1982 - 1985 SERC NATO Postdoctoral Fellowship
- 2001-2004 EU consortium. Framework 5. Immunological mechanisms of protection against Classical Swine Fever virus.
- 2002-2005 Coordinator EU consortium. Framework 5. Molecular basis for Foot and Mouth Disease Virus tropism
- Member Society for General Microbiology
- Member American Society for Microbiology
- Member British Society Immunology
- Member British Society for Cell Biology
- BBSRC Peer Review committee (Committee A) 2012-2015
- Lead Unit 6