Emeritus Professor of Immunology
I am Professor of Immunology in the Nuffield Department of Surgical Sciences where I run a research group of over 20 researchers. I also hold a Royal Society Wolfson Research Merit Award for research excellence. My research focuses on transplantation, particularly the immune response that leads to rejection and immune regulation as a strategy to achieve immunological tolerance - areas in which I have made major contributions.
I was an undergraduate in Biochemistry at the University of Birmingham and I received a DPhil from the University of Oxford in 1981 for my work on the complement system. I was elected as a Fellow of the Academy of Medical Sciences in 2002 and my professional activities include a broad array of responsibilities both nationally and internationally and have recently included: NIH Expert Panel on Transplantation Research; Better Biomarkers in Transplantation Advisory Board, University of British Columbia/Genome Canada and the INSERM Review Board.
I was the former President of The Transplantation Society and have served as a Councillor for The British Transplantation Society, The British Society for Immunology, and European Society of Organ Transplantation. Currently I am the Immediate Past President of The Transplantation Society (International), an editor of Transplantation and a former Trustee of Kidney Research UK.
My research programme focuses on the immunobiology of cell and organ transplantation.
Transplantation is the most effective therapy for treating organ failure and some forms of cancer. Transplants save lives, but the survival of a transplant is dependent on treatment with powerful immunosuppressive drugs that inhibit the immune system.
The immunosuppressive drugs currently available for clinical use are undoubtedly effective, but they act non-specifically, suppressing the entire immune system not just the response targeted at the transplant. Moreover, the drug therapy is required for the life-time of the recipient after transplantation.This means that transplant recipients experience a much higher incidence of cancer and infection and they require additional treatment for the toxic side effects of the drugs that become more pronounced with increasing time after transplantation.
The induction of tolerance to donor antigens, sometimes referred to as drug free or minimal immunosuppression, would have a major impact on improving long term graft survival and the quality of life of transplant patients.
The key areas of investigation in the laboratory at present include:
- Strategies for the induction of tolerance to alloantigens in vivo using biological therapeutic agents.
- Mechanisms of tolerance particularly the role of regulatory T cells and their therapeutic potential.
- The development and validation of biomarkers for predicting rejection and for monitoring the immune status of transplant recipients.
- Impact of the immune system on cells and tissues generated from stem cells – the response to insulin secreting cells differentiated from allogeneic embryonic stem cells and the suppressive potential of mesenchymal stem cells.
The data obtained from our studies in transplantation are also relevant to strategies for re-establishing tolerance to self antigens in patients with autoimmune disease, to preventing allergy and to promoting immune responses to tumours.
Regulatory T cells for tolerance.
Kawai K. et al, (2018), Hum Immunol, 79, 294 - 303
The Calcineurin Inhibitor Tacrolimus Specifically Suppresses Human T Follicular Helper Cells.
Wallin EF. et al, (2018), Front Immunol, 9
Selective blockade of CD28 on human T cells facilitates regulation of alloimmune responses.
Zaitsu M. et al, (2017), JCI Insight, 2
Measurement of T Cell Alloreactivity Using Imaging Flow Cytometry.
Juvet SC. et al, (2017), J Vis Exp
CD45RA Distinguishes CD4+CD25+CD127-/low TSDR Demethylated Regulatory T Cell Subpopulations With Differential Stability and Susceptibility to Tacrolimus-Mediated Inhibition of Suppression.
Arroyo Hornero R. et al, (2017), Transplantation, 101, 302 - 309