Professor of Clinical and Experimental Transplantation
Biography/Research interests
I am a reader in clinical and experimental transplantation within the department, having received a clinician scientist award from the Health Foundation in 2003. My research interests focus on the basic science of transplant rejection, with particular emphasis on how the specialised immune cells of the recipient – the T and B lymphocytes – coordinate in the development of antibody. We are increasingly aware that, after transplantation, the development of antibody directed against the transplant is associated with early failure of the transplant. Hence, a better understanding of how antibody develops will allow us to develop new strategies that aim to prevent the development of antibody, and in doing so, prolong transplant survival.
As a transplant surgeon, I also have a research interest in promoting and expanding the UK donor pool. Over the last decade, deceased donation in the UK has changed dramatically, because of the increased use of ‘donation after circulatory death’ (DCD) donors. These are donors who do not fulfil brain-stem death criteria, but whose survival prospects are futile due to catastrophic brain injury. This expansion in DCD activity has approximately doubled the numbers of UK donors annually, and currently, almost half of deceased donors in the UK are from DCD donors. This is a very different situation than occurs in the States and other European countries, and I am extremely proud that the work we have performed in Cambridge has been central to the expanded DCD UK transplant activity. Generally, retrieval teams wait one hour before abandoning donation after withdrawing life supporting treatment (WLST) in a potential DCD donor, but our research has shown that that numbers of DCD kidney transplants can be substantially increased by waiting longer from WLST, and that this does not prejudice transplant outcome (Reid et al, AJT 2011). This has informed national practice – organ retrieval teams in the UK now all wait a standard three hours from WLST. Our research has also shown that kidneys from elderly DCD donors can be used effectively and safely. To do so in Cambridge, we have adopted a strategy of performing pre-implantation biopsy analysis of kidneys from elderly DCD donors. These biopsies are analysed urgently and the results of the analysis used to inform the decision about whether to implant the kidneys as single, or dual transplants (two kidneys into the one recipient), or to discard. I am currently leading an NIHR-funded National Trial aimed at evaluating how the introduction of a National Histopathology Service impacts upon the number, and outcomes, of deceased kidney transplants performed in the UK (see http://www.pithia.org.uk/).
Key publications
Clinical
Mirshekar-Syahkal B, Summers D, Bradbury LL, Aly M, Bardsley V, Berry M, Norris JM, Torpey N, Clatworthy MR, Bradley JA, Pettigrew GJ. (2016) Local expansion in circulatory death kidney transplant activity improves wait-listed outcomes and addresses inequities of access to transplantation. Am J Transplant. Jul 18.
Mallon DH, Riddiough GE, Summers DM, Butler AJ, Callaghan CJ, Bradbury L, Saeb-Parsy K, Torpey N, Bradley JA, Pettigrew GJ. (2015) Successful transplantation of kidneys from elderly circulatory death donors by using microscopic and macroscopic characteristics to guide single or dual implantation. Am J Transplant. Nov;15(11):2931-9. PMID: 26108421.
Kosmoliaptsis V, Salji M, Bardsley V, Chen Y, Thiru S, Griffiths MH, Copley HC, Saeb Parsy K, Bradley JA, Torpey N, Pettigrew GJ. (2015) Baseline donor kidney disease confers the same transplant survival disadvantage for DCD and DBD kidneys. Am J Transplant. Mar;15(3):754-63. PMID: 25639995.
Summers DM. Watson CJ, Pettigrew GJ, Johnson RJ, Collett D, Neuberger JM, Bradley JA. (2015) Kidney Donation after Cardiac Death (DCD): State of the Art. Kidney Int. Aug;88(2):241-9. PMID: 25786101, Review.
Hamed MO, Chen Y, Pasea L, Watson CJ, Torpey N, Bradley JA, Pettigrew GJ, Saeb-Parsy K. (2015) Early Graft Loss After Kidney Transplantation: Risk Factors And Consequences’. Am J Transplant. Jun;15(6):1632-43. PMID: 25707303.
Basic Science
Chhabra M, Alsughayyir J, Qureshi MS, Mallik M, Ali JM, Negus MC, Moseley EL, Bradley JA, Bolton EM, Goddard MJ, Linterman MA, Motallebzadeh R, Pettigrew GJ. Germinal center alloantibody responses mediate progression of chronic heart allograft injury. Submitted Circulation.
Harper IG, Ali JM, Harper SJ, Wlodek E, Negus MC, Qureshi MS, Motallebzadeh R, Saeb-Parsy K, Bolton EM, Bradley JA, Clatworthy MR, Conlon TM, Pettigrew GJ. (2016) Augmentation of recipient adaptive alloimmunity by donor passenger lymphocytes within the transplant. Cell Rep. May 10;15(6):1214-27.
Ali JM, Negus MC, Conlon TM, Harper IG, Qureshi MS, Motallebzadeh R, Willis R, Saeb-Parsy K, Bolton EM, Bradley JA, Pettigrew GJ. (2016) Diversity of the CD4 T cell alloresponse: the short and the long of it. Cell Rep. Feb 9;14(5):1232-45.
Harper SJ, Ali JM, Wlodek E, Negus MC, Harper IG, Chhabra M, Qureshi MS, Mallik M, Bolton E, Bradley JA, Pettigrew GJ. (2015) CD8 T-cell recognition of acquired alloantigen promotes acute allograft rejection. Proc Natl Acad Sci U S A. Oct 13;112(41):12788-93.
