Transplant immunology, ischaemia-reperfusion injury and immunogenicity of stem cells
MA, MB BChir, PhD, FRCS
I am a Reader at the Department of Surgery, University of Cambridge and a Consultant Transplant Surgeon at Cambridge University Hospitals NHS Trust (Addenbrooke's Hospital). My clinical interests include adult kidney, pancreas and liver transplantation. I lead a research group focused on the function and immune response to stem cells and stem cell-derives cells and tissues, the mechanisms of transplant ischaemia-reperfusion injury and its amelioration, and clinical outcomes after transplantation. I am a College Lecturer at Fitzwilliam where I teach Mechanisms of Drug Action (pharmacology) to second year undergraduate medical and veterinary students. As the Director of Studies in Clinical Medicine, I am responsible for the academic progress of clinical medical students at Fitzwilliam College. Together with other medical and veterinary fellows, I am involved in the admissions process and interview applicants that wish to read Medical and Veterinary Sciences Tripos at Fitzwilliam College, University of Cambridge.
I matriculated as a medical student at Fitzwilliam College in 1993. My interest in biomedical research was developed during my Part II year studying Anatomy A (neurosciences and developmental biology) and I subsequently enrolled on the MB-PhD programme. I completed my doctoral thesis in neurophysiology of circadian rhythms in 2000 and qualified as a medical doctor in 2001. While studying for my PhD, I pursued an active interest in teaching and started supervising undergraduates at Fitzwilliam (and other colleges) in 1998. I served as MCR President in 1999, became a Fellow in 2003 and Director of Studies in Clinical Medicine in 2004. I pursued a career in surgery after graduation and was appointed as a University Lecturer in Transplant Surgery in 2012.
- MVST IB Mechanisms of Drug Action (pharmacology) - Fitzwilliam College
- Surgery to clinical medical students and surgeons in training - Addenbrooke's Hospital
My collaborative, multidisciplinary and translational research program is focused on:
- Function and immunogenicity of transplanted regenerative cellular therapies
- Ischaemia-reperfusion injury in transplantation
- Clinical outcomes after transplantation
I am additionally part of a number of other collaborative research projects that are underpinned by the use of donor human tissue.
Function and Immunogenicity of Regenerative Cellular Therapies
I am part of a broad network local and national translational and multi-disciplinary academic collaborations focused on the in vivo function and immunogenicity of stem cells. I have long-standing collaborations in Cambridge with Prof Ludovic Vallier from the Cambridge Stem Cell Institute and Dr Meritxell Huch from the Gurdon Institute, focused on regenerative cellular therapies derived from induced pluripotent stem cells and adult tissue for the treatment of diabetes and liver disease.
I am the Principal Investigator for the BETA-Protect collaboration (www.BETA-Protect.life) which brings together investigators from Cambridge, London, Oxford, Edinburgh, Aberdeen, Edinburgh and Newcastle to investigate the immunogenicity of regenerative cellular therapies for the treatment of type I diabetes and to optimize personalized immunotherapies to prevent their rejection.
I am a co-investigator in the LSFM4LIFE European Consortium (www.lsfm4life.eu) which aims to develop and optimize a novel regenerative cellular therapy for type I diabetes from adult pancreas tissue.
I am part of a multidisciplinary collaboration with Prof Nigel Slater from the Department of Chemical Engineering and Biotechnology in Cambridge to investigate a novel method for the cryopreservation of human haematopoietic stem cells (HSCs) and cellular aggregates, including pancreatic islets in collaboration with Mr John Casey from the Scottish Islet Laboratory.
Much of my research programme in regenerative medicine is underpinned by the use of human HSCs, including in collaboration with Dr Elisa Laurenti from the Cambridge Stem Cell Institute. A particular focus of my group is using human HSCs for the creation and characterization of experimental models of the human immune compartment, also known as ‘humanised mice’. I am the co-founder and coordinator of the annual UK Humanized Mouse Symposium (www.hms.event.cam.ac.uk), which aims to share expertise and encourage collaborations focused on the characterization and use of this important experimental model.
I have a long-standing collaboration with Dr Mike Murphy from the Cambridge MRC Mitochondrial Unit to investigate the mechanisms of ischaemia-reperfusion injury (IRI) in organ transplantation and to develop therapeutic approaches for its amelioration. My research utilizes a number of murine, porcine and human models of IRI in collaboration with Prof Mike Nicholson from the University of Cambridge and includes the use of human deceased organs retrieved but declined for transplantation.
I am an investigator in the Mitochondrial Therapies Group which is focused on developing mitochondria-targeted strategies to minimize IRI in transplantation, myocardial infarction and stroke.
I co-founded and coordinate the annual UK Ex Vivo Normothermic Perfusion Symposium (www.evnp.event.cam.ac.uk) which aims to share expertise and encourage collaborations focused on the use of ex vivo organ perfusion in transplantation.
I lead a number of clinical transplantation studies including randomized control trials, cohort studies and retrospective service evaluations examining outcomes after kidney, pancreas and liver transplantation using local and national data.
I am part of a medico-legal academic collaboration with Dr Matthew Dyson from and Dr Kathleen Liddell from the Faculty of Law at the University of Cambridge to explore the legal regulation of transplantation.
I am part of a collaboration with Prof Hamid Sabourian from the Department of Economics at the University of Cambridge to apply Game Theory to decision making and outcome prediction in transplantation.
Translational Research Using Human Tissue
I am the Principal Investigator on more than 10 studies with and National Research Ethical Committee (NREC) approval for use of donor human tissue in research. I am the Founder and Director of the Cambridge Biorepository for Translational Medicine (www.cbtm.group.cam.ac.uk), which was established to support world-class multidisciplinary research collaborations Cambridge and beyond through the provision of infrastructure, expertise and access to fresh human tissue. This biorepository supports leading research by more than 10 laboratories in Cambridge and beyond, focused on transplantation, regenerative medicine, cancer, developmental biology, metabolic sciences, immunology and gastrointestinal physiology.
- Miss Nikola Dolezalova (PhD Student)
- Miss Kathleen Elliott (Clinician PhD Student)
- Mr Nikitas Georgakopoulos (Research Assistant)
- Mr Mazin Hamed (Clinician PhD Student)
- Mr Jack Martin (Clinician PhD Student)
- Miss Olivia Tysoe (PhD Student)
Department of Surgery
- Prof J Andrew Bradley
- Dr Eleanor Bolton
- Dr Sarah Hosgood
- Prof Michael Nicholson
- Mr Gavin Pettigrew
- Prof Christopher Watson
Cambridge Stem Cell Institute
- Dr Meritxell Huch
- Dr Elisa Laurenti
- Prof Ludovic Vallier
MRC Mitochondrial Biology Unit
- Dr Michael Murphy
MRC Cancer Unit
- Dr Christian Frezza
Department of Medicine
- Dr Menna Clatworthy
- Dr Thomas Krieg
- Dr Dr Will Gelson
- Dr Michael Allison
Department of Chemical Engineering and Biotechnology
- Dr Krishnaa Mahbubani
- Prof Nigel Slater
Department of Histopathology
- Dr Rebecca Brais
- Dr Susan Davies
Department of Economics
- Prof Hamid Sabourian
Faculty of Law
- Dr Matthew Dyson
- Dr Kathleen Liddell
National and International Collaborators
- LSFM4LIFE Consortium (www.LSFM4LIFE.eu)
- BETA-Protect Collaboration (www.BETA-Protect.life)
- Mitochondrial Therapies Group (www.mrc-mbu.cam.ac.uk)
- Cambridge Biorepository for Translational Medicine (www.CBTM.group.cam.ac.uk)
Annual National Meetings Coordinated
- UK Ex Vivo Normothermic Perfusion Meeting (www.evnp.event.cam.ac.uk)
- UK Humanised Mouse Symposium (www.hms.event.cam.ac.uk)
Selected recent publications
1. Essential Surgery. 5th Ed. Quick RG, Reed JB, Harper SJF & Saeb-Parsy K. Churchill Livingstone, 2013, 688 pp, ISBN 0702046744.
2. Instant Pharmacology. Saeb-Parsy K, Assomull RG, Kelly E, Khan FZ & Saeb-Parsy K. John Wiley & Sons Ltd, 1999, 368 pp, ISBN: 0471976393.
1. Dyson M, Watson CJE, Liddell K, Padfield N, Bradley JA & Saeb-Parsy K (2015). Transplanting suboptimal organs: medico-legal implications. The Lancet 386:719-21..
2. Sampaziotis F, Brito MC, Bertero A, Madrigal P, Saeb-Parsy K, Soares F, Schrumpf E, Melum E, Karlsen TH, Bradley JA, Gelson WTH, Davies S,Baker A, Kaser A, Alexander GJ, Hannan NRF, Vallier L (2015) Human Induced Pluripotent Stem Cell derived cholangiocytes for 1 disease modeling and drug validation. Nature Biotechnology 33:845-52.
3. Dare A, Logan A, Prime T, Rogatti S, Goddard M, Bolton E, Bradley JA, Pettigrew GJ, Murphy M, Saeb-Parsy K (2015) The mitochondria-targeted antioxidant MitoQ decreases ischemia-reperfusion injury in a murine syngeneic heart transplant model. Journal of Heart and Lung Transplantation 34:1471-80.
4. Barlow AD, Hamed MO, Mallon DH, Brais RJ, Gribble FM, Scott MA, Howat WJ, Bradley JA, Bolton EM, Pettigrew GJ, Hosgood SA, Nicholson ML, Saeb-Parsy K (2015) Use of ex vivo normothermic perfusion for quality assessment of discarded human donor pancreases. American Journal of Transplantation 15:2471-82.
5. 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. American Journal of Transplantation 15:2931-9.
6. Dare AJ, Bolton EA, Pettigrew GJ, Bradley JA, Saeb-Parsy K, Murphy MP (2015) Protection against renal ischemia-reperfusion injury in vivo by the mitochondria targeted antioxidant MitoQ. Redox Biology 5:163-168.
7. 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. American Journal of Transplantation 15:1632-43.
8. Chouchani ET, Pell VR, Gaude E, Aksentijević D, Sundier S, Rob EL, Logan A, de Costa SE, Nadtochiy SM, Smith AC, Eyassu F, Ord ENJ, Shirley R, Hu C-H, Dare AJ, James AM, Rogatti S, Hartley RC, Eaton S, Brookes PS, Davidson SM, Duchen MR, Saeb-Parsy K, Shattock MJ, Robinson AJ, Work LM, Frezza C, Krieg T & Murphy MP (2014) Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature 515:431-5.
9. Li J, Kent DG, Godfrey AL, Manning H, Nangalia J, Aziz A, Chen E, Saeb-Parsy K, Fink J, Sneade R, Hamilton T, Pask D, Silber Y, Zhao X, Ghevaert C, Liu P, Green AR (2014). JAK2V617F-homozygosity drives a phenotypic switch between myeloproliferative neoplasms in a murine model, but is insufficient to sustain clonal expansion. Blood 123:3139-51.
10. Dare A, Pettigrew GJ, Saeb-Parsy K (2014) Pre-operative assessment of the deceased donor kidney: from macroscopic appearance to molecular biomarkers. Transplantation 97:797-807.
11. Callaghan CJ, Harper SJ, Saeb-Parsy K, Hudson A, Gibbs P, Watson CJ, Praseedom RK, Butler AJ, Pettigrew GJ, Bradley JA. The discard of deceased donor kidneys in the UK. Clinical Transplantation 28:345-53.
12. Chhabra M, Conlon TM, Saeb-Parsy K, Pettigrew GJ (2013) BAFF and Associated TNF Superfamily Members in Renal Transplantation: An End to BLySful Ignorance. Transplantation 96:853-9.
13. Sivaganesh S, Harper SJ, Conlon TM, Callaghan CJ, Saeb-Parsy K, Negus MC, Motallebzadeh R, Bolton EM, Bradley JA, Pettigrew GJ (2013) Copresentation of intact and processed MHC alloantigen by recipient dendritic cells enables delivery of linked help to alloreactive CD8 T cells by indirect-pathway CD4 T cells. Journal of Immunology 190:5829-38.
14. Conlon T, Cole J, Motallebzadeh J, Harper I, Callaghan C, Bolton E, Bradley JA, Saeb-Parsy K, Pettigrew GJ (2012) Unlinked memory helper responses promote long-lasting humoral alloimmunity. Journal of Immunology 189:5703-12.
15. Conlon TM, Saeb-Parsy K, Cole JL, Motallebzadeh R, Qureshi MS, Rehakova S, Negus MC, Callaghan CJ, Bolton EM, Bradley JA, Pettigrew GJ (2012). Germinal center alloantibody responses are mediated exclusively by indirect-pathway CD4 T follicular helper cells. Journal of Immunology 15, 2643-52.
16. Saeb-Parsy K, Kosmoliaptsis V, Sharples LD, Watson CJ, Clatworthy MR, Taylor CJ, Pettigrew GJ, Bradley JA (2010) Donor Type Does Not Influence the Incidence of Major Urologic Complications After Kidney Transplantation. Transplantation 90, 1085-90.
17. Win TS, Rehakova S, Negus M, Saeb-Parsy K, Goddard M, Conlon M, Bolton EM, Bradley JA & Pettigrew GJ (2009) Donor CD4 T cells contribute to cardiac allograft vasculopathy by providing help for autoantibody production. Circulation: Heart Failure 2:361-9.
18. Saeb-Parsy K, Jah A, Butler AJ, Large S, Pettigrew GJ, Praseedom RK, Watson CJ & Jamieson NV (2009) Use of a donor aortic interposition allograft to treat stenosis of the suprahepatic inferior vena cava after liver transplantation. Liver Transplantation 15, 662-5.
19. Saeb-Parsy K, Bolton EM (2009) Antiplatelet Therapy in Transplantation: New Tricks from Old Drugs? Transplantation 87, 633-5.