Prof. Reza Motallebzadeh, Prof. Stephen Marks, Dr Rhys Evans, and Dr Daniyal Jafree lead collaborative, multidisciplinary and translational research into chronic kidney disease and renal transplantation. We hope to understand the immune mechanisms underlying development of allograft failure and rejection in solid organ transplantation. Our aim is to develop new knowledge and practices to improve long-term outcomes for patients receiving a kidney transplant.
Professor Reza Motallebzadeh explains on this podcast, hosted by Jonathan McCrea of Futureproof, exciting new innovations in organ transplantation
Our work
Despite improvements in short- and medium-term graft survival rates after renal transplantation, long-term graft survival has remained largely unchanged for the last twenty years, with recipients either dying with a functioning graft or suffering graft loss due to infection and/or chronic alloimmune rejection. Furthermore, balancing the benefits and adverse effects of immunosuppression to extend graft survival remains a challenge.
We focus on collaborative, multidisciplinary, and translational research in chronic kidney disease and renal transplantation. The research themes are underpinned by a commitment to developing innovative collaborations with academic and industrial partners and are primarily focused on understanding mechanisms of allograft failure and improving long-term graft and patient survival outcomes in renal transplantation.
Our Centre is currently working on the following areas of translational science and clinical research:
Delineating the role of the host microbiota in renal transplantation.
Identification of novel blood, urine, and tissue biomarkers of acute rejection and transplant injury to assist personalised immunosuppression in paediatric renal transplant recipients.
Understand the role of tissue-resident NK cells in the control of human cytomegalovirus infection.
Spatial and molecular profiling of kidney lymphatic vessels in kidney allograft rejection.
The BKV viral serotype mismatch of the UK donor and renal transplant recipient population predicts post-transplant BKV viraemia.
Investigating the impact of sodium on alloimmune responses.
Study of B cell responses to SARS-CoV-2 vaccination in end-stage kidney disease and defining the basis of a hyporesponsive immune phenotype.
Donor-derived cell-free DNA: a liquid biopsy following solid organ transplantation.
Developing 3D renal organoids to study renal fibrosis.
Qualitative assessment of the impact of human cytomegalovirus infection in kidney transplantation.
The role of complement immune attack and regulation in kidney transplant biopsies.
Investigating the modifiable psychosocial variables influencing access to and outcomes after kidney transplantation in children.
The composition of the microbiota and their metabolites could elicit signals that promote either an enhanced or diminished immune response against a kidney transplant. We aim to develop a better understanding of the changes to the gut microbiota and metabolites produced by them that can predict the course and heterogeneity of alloimmune responses.
Collaborators
Professor Reza Motallebzadeh
Dr Mona Bajaj-Elliot (GOS Institute of Child Heath, UCL)
Dr Anne Pesenacker (Institute of Immunity & Transplantation, UCL)
Professor Simon Eaton (GOS Institute of Child Heath, UCL)
Professor Alan Salama (Department of Renal Medicine, UCL)
Professor Jennifer Rohn (Department of Renal Medicine, UCL)
Professor Claudio Mauri (Institute of Immunity & Transplantation, UCL)
Professor Alan Salama (Department of Renal Medicine, UCL)
Professor Stephen Marks (GOS Institute of Child Health, UCL)
The lymphatic vasculature clears fluid and macromolecules from the tissue microenvironment and acts as a highway for migrating leukocytes. There is however limited information beyond traditional immunohistochemical assessment in human organs such as the kidney. We use three-dimensional imaging and single-cell RNA-sequencing to study lymphatics in the human kidney, with the aim of delineating novel structural and molecular features that might be of relevance to chronic alloimmunity.
Collaborators
Professor Reza Motallebzadeh
Professor David Long (GOS Institute of Child Heath, UCL)
Dr Daniyal Jafree (GOS Institute of Child Heath, UCL)
Professor Menna Clatworthy (Cambridge Institute of Therapeutic Immunology & Infectious Disease, Cambridge University)
Professor Stephen Marks (GOS Institute of Child Health, UCL)
Human cytomegalovirus (HCMV), one of the most frequent infectious complications after kidney transplantation, can lead to graft rejection and death. Natural killer (NK) cells can counter HCMV and are present in circulating blood, but we have also recently identified NK cells within donor kidneys. We aim to understand if kidney-resident NK cells can better control HCMV than their circulating counterparts. We can then determine if some donor's kidneys because they are better armed with kidney-resident NK cells, are better at controlling HCMV in recipients. Our work will ultimately help in the design of novel therapies against HCMV.
Collaborators
Professor Reza Motallebzadeh
Dr Matthew Reeves (Institute of Immunity & Transplantation, UCL)
Dr Dimitra Peppa (Institute of Immunity & Transplantation, UCL)
Dr Victoria Male (Faculty of Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College)
BK polyomavirus (BKV) has a seroprevalence of >80%. Viraemia occurs in 10% of kidney transplantation recipients and may result in premature allograft failure. Given emerging evidence that the disease is donor-derived, we aim to determine the correlation between donor/recipient BKV serotype mismatch and infection risk, using neutralisation profiles to infer viral serotypes individuals have encountered.
Collaborators
Professor Alan Salama (Department of Renal Medicine, UCL)
Dr Matthew Reeves (Institute of Immunity and Transplantation, UCL)
Recent research by our team and others has shown that increased extracellular sodium, which may be the result of a high salt (sodium chloride) diet, can impact immunity. The overall effect of increasing extracellular sodium is to make the immune system more inflammatory and we have shown that patients with inherited salt-losing diseases have a dysregulated immune system with dampened IL-17 responses. We are now investigating how sodium impacts alloimmune responses, and we will undertake a pilot study to determine the effect of salt depletion on immunity in kidney transplant recipients. This work is funded through an innovation grant from Kidney Research UK and a project grant from St. Peter’s Trust.
Collaborators
Dr Rhys Evans (Department of Renal Medicine, UCL)
Professor Alan Salama (Department of Renal Medicine, UCL)
Professor Reza Motallebzadeh (Department of Renal Medicine, UCL, Research Dept of Surgical Biotechnology, UCL & Institute of Immunity and Transplantation, UCL)
Professor Stephen Walsh (Department of Renal Medicine, UCL)
A novel point-of-care device to monitor urinary chemokines serially in renal transplant recipients and identify recipients with incipient allograft injury. Immune-based biomarkers offer the potential for identifying patients at risk for graft rejection and for individualizing immunosuppression therapy.
Collaborators
Professor Reza Motallebzadeh
Professor Manish Tiwari (Dept of Mechanical Engineering, UCL)
Professor Stavroula Balabani (Dept of Mechanical Engineering, UCL)
Dr Mark Harber (Department of Renal Medicine, UCL)
Dr Arnab Guha (Department of Mechanical Engineering, Birla Institute of Technology & Science, India)
Professor Stephen Marks (GOS Institute of Child Health, UCL)
This study aims to understand the aetiopathogenesis of acute rejection and transplant injury to improve longer-term outcomes in children and young people, funded by Kidney Research UK Laurence Isaacson PhD award.
Collaborators
Professor Stephen Marks (GOS Institute of Child Health, UCL)
Professor David Long (GOS Institute of Child Health),
Professor Alan Salama (Department of Renal Medicine, UCL),
Professor Reza Motallebzadeh (Department of Renal Medicine, UCL, Research Dept of Surgical Biotechnology, UCL & Institute of Immunity and Transplantation, UCL)
The aim is to develop, characterize, and validate a novel in vitro 3D human kidney organoid culture system ultimately aimed at screening for compounds capable of modulating the tubulointerstitial microenvironment crosstalk that perpetuates the development of fibrosis in chronic kidney disease.
Collaborators
Professor Reza Motallebzadeh
Professor Jill Norman (UCL Centre for Experimental Nephrology)
Professor Krista Rombouts (UCL Institute for Liver and Digestive Health)
Cytomegalovirus (CMV) is a common global viral infection; it can remain inactive following an initial infection but then can be reactivated post-transplantation or can be transmitted from the transplanted organ, both causing major problems and disease in kidney transplant recipients on immunosuppression treatment. The severity may lead to failure of the kidney transplant or in some cases death. We know from patients that they worry about the risk of this frequent complication after a kidney transplant. We will be conducting a qualitative study to understand how CMV infection after kidney transplantation impacts patient health, determine what is the impact on their quality of life, and to what degree do the usual symptoms of CMV infection, such as reduced physical activity and mobility as well as mental fatigue and stress, affect their daily lifestyle.
Collaborators
Professor Reza Motallebzadeh
Professor Prof Cecilia Vindrola (Department of Targeted Intervention, UCL Division of Surgery & Interventional Sciences)
Dr Tanzina Haque (Royal Free London NHS Foundation Trust)
Dr Matthew Reeves (Institute of Immunity & Transplantation, UCL)
This study investigates which factors are important and potentially modifiable to improve access to kidney transplantation and transplant outcome measures, funded by National Institute of Health and Care Research.
Collaborators
Professor Stephen Marks (GOS Institute of Child Health, UCL)
This study, called European Paediatric Access to Kidney Transplantation (EuPAKT) looks at the infrastructure of non-transplant and transplant paediatric nephrology centres in Europe, funded by the European Society for Paediatric Nephrology.
Collaborators
Professor Stephen Marks (GOS Institute of Child Health, UCL)
European Society for Paediatric Nephrology and CERTAIN (Cooperative European Paediatric Renal TransplAntINitiative)
A prospective multi-centre observational cohort study to determine whether ultrasound surveillance can reliably predict arteriovenous fistulae failure in patients with chronic kidney disease.
A randomised controlled trial comparing clinical (one-year functional patency rate) and cost-effectiveness of regional versus local anaesthesia for primary arteriovenous fistula formation.
An open, stepped-wedge cluster, randomised trial to determine if the introduction of a national pre-implantation biopsy histopathology service increases numbers, and improve outcomes, of kidney transplants performed in the UK.
Should we ligate haemodialysis fistulas in patients once they have been transplanted successfully? This feasibility study aims to objectively detail how arteriovenous fistula (AVF) disconnection in renal transplant recipients can change cardiorespiratory fitness and physical capacity, thereby potentially increasing patients' activity levels and improving quality of life.
A Multicentre, Open-Label, Single Ascending Dose, Dose Ranging, Phase I/IIa Study to Evaluate the Safety and Tolerability of an Autologous Antigen-Specific Chimeric Antigen Receptor T Regulatory Cell Therapy (TX200-TR101) in Living Donor Renal Transplant Recipients.
A multicentre, non-inferiority, two-parallel-arm randomised trial of cardiac screening in adults with chronic kidney disease who are awaiting kidney transplant.
Fabes J, Wittenberg M, Motallebzadeh R (2022). Anaesthetic considerations and post-operative care of living kidney donors. In Lipkin G, Sharif A (eds.), Living Kidney Donation - A Practical Guide. Springer Nature.
Jafree D, Kolatsi-Joannou M, Stewart B, Pomeranz G, Marinas Del Rey L ... Scambler P (2021). Interrogating the spatial and molecular profile of kidney lymphatic vessels in health and transplant rejection.
Our members contribute to the MBBS and master's degrees within the Division of Medicine. We provide BSc and MSc/MRes research project supervision. We also have an established track record in providing high-quality training to PhD students interested in basic, translational, and clinical research in the areas of transplantation. Our teaching involvement includes the following.
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