The University of Southampton
Medicine

Dr Edd James BSc (Hons), PhD

Associate Professor in Cancer Immunology

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As an immunologist, my research examines how antigens are processed and presented to the immune system. An associate professor in cancer immunology, my research identifying ways in which tumours escape the immune response drives my passion to develop more potent and effective cancer immunotherapies.

Harnessing the power of your immune system is forging the way to a revolution in cancer therapy.

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.

BSc(Hons), Microbiology, University of Bristol 1997
PhD, Immunology, Imperial College 2001

Appointments held

Research Fellow, MRC CSC Hammersmith Hospital, London, 2001-2002

Wellcome Trust International Travelling Fellow, University of California at Berkeley, 2002-2005

Wellcome Trust International Travelling Fellow, University of Southampton, 2005-2006

Lecturer in Cancer Immunology, University of Southampton, 2006-present

Research

Responsibilities

Publications

Teaching

Contact

Research interests

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.

Academic unit(s)

Cancer Sciences Academic Unit

Affiliate academic unit(s)

Cancer Sciences Research group

Postgraduate student supervision

Current

Gessa Sugiyarto PhD
Dannielle Wellington PhD
Faith Bateman PhD


Faculty of Medicine

Study in depth (MMedSc/BMedSc). Head of Immunology and Immunotherapy field
BM4. Group Facilitator

University of Southampton

Member of Senate

Articles

BmedSc/MmedSc. Provides laboratory based projects. Offers 2-3 project placements that investigate the induction of anti-tumour immunity

BSc Biomedical Science. Lectures on transplantation

BM5. Lectures on Antigen Presentation and autoimmunity seminar

BM4. Group Facilitator

Integrated PhD Cancer Pathway. Involved in teaching of immunology module and supervisor of rotation projects

Dr Edd James
Phone: (+44) 023 8120 4309 Fax: (+44) 023 8120 5152
Email: eddjames@soton.ac.uk

Room Number:9580 SGH/CSB/MP824

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