Professor Neil Williams
Professor of Immunology
School of Cellular and Molecular Medicine,
University of Bristol, Medical Sciences Building,
Bristol, BS8 1TD
phone: +44 (0)117 33 12064 (internal 12064)
Professor Neil Williams graduated from the University of Birmingham and obtained a PhD in Immunology in 1989. He was appointed as a Lecturer in Immunology at Bristol in 1991 and has since been promoted through to being Professor of Immunology. His research interests in the modulation of immune responses in autoimmune and allergic disease have led to substantial funding, a large number of publications and international recognition. This work has also led to the granting of 5 international patents and the formation of two spin-out companies. Aegis Pharmaceuticals Ltd was acquired in 2001 by Hunter-Fleming Ltd, and then led to the formation of Trident Inc. in 2006 with whom Neil still works closely as a member of the Scientific Board. KWS BioTest Ltd was launched in 2003 with Neil remaining as Director of Science. Neil is also currently a member of the Meningitis Research Foundation's Scientific Advisory Group, and an Honorary Vice President of the London International Youth Science Forum.
Research ongoing within the Williams laboratory focuses on basic and applied aspects of immunity at mucosal surfaces. Current research within the laboratory is focused into two main areas:
- Studies of the unique immunological properties of the cholera-like enterotoxins. Cholera toxin (Ctx) and its relative, Escherichia coli heat-labile enterotoxin (Etx), are highly effective mucosal adjuvants triggering strong protective immunity to unrelated antigens, and their B-subunits (CtxB and EtxB respectively) can be used to prevent or treat inflammatory diseases. We are investigating these molecules as adjuvants (for herpes simplex virus and influenza virus vaccination), immunotherapeutics (for treating autoimmunity and allergy) and as delivery vehicles for the generation of cytotoxic T cell responses to tumours and viruses. In addition, we are currently defining at the cellular and cell signaling level the precise processes by which these molecules modulate cells of the immune system.
Our work with EtxB has established that this remarkable protein is able to inhibit or treat disease in models of rheumatoid arthritis, type I diabetes, Crohn's disease, asthma and autoimmune uveitis. This ability stems from the fact that EtxB generates an environment in tissue sites local to its delivery in which T cell diffierentiation is altered in favour of the generation of T regulatory cells. These cells then circulate through the body and control inflammation at distant sites. We continue to try to uncover the mechanisms involved, and in collaboration with Trident Inc. we are now preparing for clinical trials with EtxB as a treatment for inflammatory disease.
Other work has shown that when antigens are conjugated to EtxB, this facilitates their delivery into class I MHC processing pathways and that this can be used as an effective means of stimulating anti-viral and anti-tumour cytotoxic T cell responses. We are working with CRUK in order to develop this approach as a means of generating novel vaccination and immunotherapy approaches against human cancers.
- Studies of mucosal immunity to nasopharyngeal pathogens. We have established a strong interest in understanding the basis of immunity to Neisseria meningitidis group B (NmB) and are extending the approaches that we have developed in this area to understand important issues for vaccine design and also the similarities and differences that there are to the immune response to a related commensal, Neisseria lactamica, and another pathogen of the same site, the pneumococcus. This work is a close collaboration between the Williams group and that of Professor Robert Heyderman. We have developed novel ways of investigating the nature of mucosal T cell immunity in humans through the use of tonsillectomy samples and have established the basis of naturally acquired immunity to NmB. As part of this work, we have shown that the immune response to NmB is at least initially characterised by high levels of T regulatory activity balancing a pro-inflammatory phenotype. We are continuing to define the mechanisms involved in the induction of this response through studies of the interaction between NmB and dendritic cells and the nature of the T regulatory responses. In addition, we are using vaccination in humans as a means of probing the nature of immunity to these important organisms.
View all publications held on the University of Bristol's IRIS database
- Horton, R.E., Vidarsson, G., Virji, M., Williams, N.A. and Heyderman, R.S. (2009) IgA1 antibodies specific for outer membrane protein PorA modulate the interaction between Neisseria meningitidis and the epithelium. Microbial Pathogenesis, 46, 253-260.
- Janicki, C.N., Jenkinson, S.R., Williams, N.A. and; Morgan, D.J. (2008) Loss of CTL function amongst high avidity tumor-specific CD8+ T cells following tumor infiltration. Cancer Research, 68, 2993-3000.
- Hobbs, C.G., Groves, E., Davenport, V., Bailey, M., Williams, N.A., Birchall, MA and Heyderman, RS. (2008) Tonsil T cell immunity to Human Papillomavirus in the absence of detectable virus in healthy adults', Laryngoscope, 118 (3), 459-463.
- Davenport, V., Groves, E., Horton, R.E., Hoobs, C.G., Guthrie, T., Findlow, J., Borrow, R., Naess, L.M., Oster, P., Heyderman, R.S. and Williams, N.A. (2008) Mucosal immunity in healthy adults after parenteral vaccination with outer-membrane vesicles from Neisseria meningitidis serogroup B. The Journal of Infectious Diseases, 198 (5), 731-740.
- Raveney, B.J., Richards, C.M., Aknin, M.L., Copland, D.A., Burton, B.R., Kerr, E., Nicholson, L.B., Williams, N.A. and Dick, A.D. (2008) The B subunit of Escherichia coli heat-labile enterotoxin inhibits Th1 but not Th17 cell responses in established experimental autoimmune uveoretinitis. Investigative Opthalmology and Visual Science, 49 (9), 4008-4017.
- Davenport, V., Groves, E., Hobbs, C.G., Williams, N.A. and Heyderman, R.S. (2007) Regulation of Th-1 T cell-dominated immunity to Neisseria meningitidis within the human mucosa. Cell. Microbiol. 9, 1050-1061.
- Milling, S.W.F., Yrlid, U., Jenkins, C., Richards, C.M., Williams, N.A. and MacPherson, G. (2007) Regulation of intestinal immunity: Effects of the oral adjuvant Escherichia coli heat-labile enterotoxin on migrating dendritic cells. Eur. J. Immunol. 37, 87-99.
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