James, Edd - University of Southampton

个人简介

Dr. James graduated in Microbiology from the University of Bristol in 1997, he completed his PhD at Imperial college London in 2001 working on the induction of transplantation tolerance. He completed his postdoctoral training at the University of California at Berkeley and University of Southampton. He held a lectureship in cancer immunology in Southampton before becoming an associate professor in 2015. He sits on the Editorial board of Journal of vaccines and immunology and on the Editorial advisory board of Immunology news. Dr. James leads a group that focuses on understanding the mechanisms behind the immunodominance of antigens in tumours. In addition, his group investigates the role of antigen processing and presentation plays in generating immune responses. His research is based within the Faculty of Medicine campus; which consists of clinical and non-clinical scientists with post- and undergraduate students. Potential students, post-doctoral scientists or clinical scientists who are interested in joining his group are encouraged to contact Dr. James.

研究领域

Dr. James’ research has a focus on antigen processing and presentation, relating to the understanding of these processes and manipulation of them in order to treat. Regulatory T cell suppression in anti-tumour responses Using a murine model of colon carcinoma (CT26) we have previously identified differential suppression, by regulatory T cells (Tregs), of cytotoxic (CD8) T cells that infiltrate the tumour. Characterisation of a cryptic tumour epitope showed that this Treg suppression prevents an effective anti-tumour T cell response and ultimately rejection of the tumour. The ability of Tregs to “switch off” protective anti-tumour CD8 T cells highlights important differences within an anti-tumour T cell response. We are currently investigating the precise mechanism/s by which Tregs suppress the anti-tumour T cell responses and why less effective anti-tumour T cells are unaffected by this suppression. We have recently identified several differences in suppressed CD8 T cells compared to those that are resistant; including the affinity/avidity of the T cell : peptide/MHC interaction and the induction of clonal exhaustion. Antigen processing and presentation In the endoplasmic reticulum, MHC class I molecules bind to antigenic peptides derived from viral, bacterial and mutated proteins as well as from intracellular proteins. Many proteins are involved in the processing of antigens into peptides for loading onto MHC class I molecules. One key protein, ERAP1, (and ERAP2 in humans) trims peptide precursors that are too long to the correct length for MHC class I loading, therefore playing a crucial role in defining the repertoire of peptides available for MHC class I loading and presentation. Using the murine CT26 tumour we have shown that attenuation of ERAP1 (ERAAP in mouse) activity both in vitro and in vivo leads to tumour rejection through increased presentation of protective peptides. In addition, our experiments have shown that attenuation of ERAP1 in established tumours in vivo results in prolonged survival and reduced tumour burden in mice, highlighting a potential therapeutic strategy. We are also investigating the role of antigen processing in human cancers and autoimmune conditions. Genetic studies have identified mutations within ERAP1 associated with many diseases; how these mutations in ERAP1 affect disease is currently not known. We have shown that ERAP1 is polymorphic in humans and consists of multiple alleles containing these mutations. These alleles have a wide spectrum of peptide trimming activities identifying three functional groups; those that are efficient, hypo and hyperactive trimmers. We are currently examining how these mutations affect the trimming function and alter substrate specificity. In addition we are studying the role of these polymorphic ERAP1 proteins in pathogenesis of autoimmune diseases and tumour incidence/progression.

近期论文

查看导师新发文章（温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Reply to Robinson and Brown: it is the combination of ERAP1 allotypes that identifies individuals with ankylosing spondylitis. - Reeves, Emma, Colebatch-Bourn, Alexandra, Elliott, Tim, Edwards, Christopher J. and James, Edward Published:2015Publication:Proceedings of the National Academy of SciencesVolume:112, (15)Page Range:E1817doi:10.1073/pnas.1502270112PMID:25767099 Functionally distinct ERAP1 allotype combinations distinguish individuals with Ankylosing Spondylitis - Reeves, Emma, Colebatch-Bourn, Alexandra, Elliott, Tim, Edwards, Christopher J. and James, Edward Published:2014Publication:Proceedings of the National Academy of SciencesVolume:111, (49)Page Range:17594-17599doi:10.1073/pnas.1408882111PMID:25422414 ERAP1 in the pathogenesis of ankylosing spondylitis - Reeves, Emma, Elliott, Tim, James, Edward and Edwards, Christopher J. Published:2014Publication:Immunologic ResearchVolume:60, (2)Page Range:257-269doi:10.1007/s12026-014-8576-2PMID:25434650 Critical role of endoplasmic reticulum aminopeptidase 1 in determining the length and sequence of peptides bound and presented by HLA-B27 - Chen, Liye, Fischer, Roman, Peng, Yanchun, Reeves, Emma, McHugh, Kirsty, Ternette, Nicola, Hanke, Tomas, Dong, Tao, Elliott, Tim, Shastri, Nilabh, Kollnberger, Simon, James, Edward, Kessler, Benedikt and Bowness, Paul Published:2014Publication:Arthritis & RheumatologyVolume:66, (2)Page Range:284-294doi:10.1002/art.38249PMID:24504800 Rationally designed inhibitor targeting antigen-trimming aminopeptidases enhances antigen presentation and cytotoxic T-cell responses - Zervoudi, E., Saridakis, E., Birtley, J., Seregin, S., Reeves, E., Kokkala, P., Aldhamen , Y.A., Amalfitano, A., Mavridis, I., James, E., Georgiadis, D. and Stratikos, E. Published:2013Publication:Proceedings of the National Academy of SciencesPage Range:1-9doi:10.1073/pnas.1309781110PMID:24248368 Naturally occurring ERAP1 haplotypes encode functionally distinct alleles with fine substrate specificity - Reeves, E., Edwards, C.J., Elliott, T. and James, E. Published:2013Publication:Journal of ImmunologyVolume:191, (1)Page Range:35-43doi:10.4049/jimmunol.1300598PMID:23733883