Can a type of immune cell in the kidney control viral infections in patients who receive a transpla…
Prof. Reza Motallebzadeh has received a Michael Nicholson PhD Studentship Award of £94,000 to study how a group of immune cells in the kidney control viral infections in kidney transplant patients.
Our work
Despite improvements in short- and medium-term graft survival rates after solid-organ 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. Balancing the benefits and adverse effects of immunosuppression to extend graft survival remains a challenge.
IIT researchers work closely with the clinical transplant teams at the Royal Free Hospital, which is a large UK transplantation centre performing more than 250 liver and kidney transplants from HLA mismatched donors.
We explore the role of Natural Killer cells, T cells and B cells in the immune response against transplanted organs, and how they can control viral pathogenesis within an immunosuppressed milieu. Understanding these critical aspects of human alloimmune and anti-viral responses will inform development of new strategies to mitigate against common complications after organ transplantation such as acute rejection and opportunistic viral infections.
We also study how epithelial cells, lining cells on the inner and outer surfaces of the body, are produced from self-renewing stem cells in various organs to specialise into different functions. It is hoped that this work will lead to novel cell-based therapies to repair or regenerate damaged or faulty organs in the body.
Projects
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.
Lead Investigator
- Prof. Reza Motallebzadeh (Institute of Immunity & Transplantation / Division of Surgery & Interventional Science, UCL)
Collaborators
- Dr Mona Bajaj-Elliot (GOS Institute of Child Heath, UCL)
- Dr Anne Pesenacker (Institute of Immunity & Transplantation, UCL)
- Prof. Simon Eaton (GOS Institute of Child Heath, UCL)
- Prof. Alan Salama (Department of Renal Medicine, UCL)
- Prof. Jennifer Rohn (Department of Renal Medicine, UCL)
- Prof. Claudio Mauri (Institute of Immunity & Transplantation, UCL)
Funding
- UCL National Institute of Health Research Biomedical Research Centre (III Theme)
- St Peter's Trust
- Royal Free Charity
We use three-dimensional imaging and single-cell RNA-sequencing to study lymphatics in the human kidney to delineate novel structural and molecular features relevant to chronic alloimmunity.
Lead Investigator
- Prof. Reza Motallebzadeh (Institute of Immunity & Transplantation / Division of Surgery & Interventional Science, UCL)
Collaborators
- Prof. David Long (GOS Institute of Child Heath, UCL)
- Dr Daniyal Jafree (GOS Institute of Child Heath, UCL)
- Prof. Menna Clatworthy (Cambridge Institute of Therapeutic Immunology & Infectious Disease, Cambridge University)
Funding
- Kidney Research UK
- Rosetrees Trust
Human Cytomegalovirus (CMV) can remain inactive following an initial infection but be reactivated post organ transplantation or transmitted from the transplanted organ to the recipient. Both scenarios cause major problems in kidney transplant recipients on immunosuppression treatment. We aim to understand how CMV infection after kidney transplantation impacts patient health and quality of life.
Lead Investigator
- Prof. Reza Motallebzadeh (Institute of Immunity & Transplantation / Division of Surgery & Interventional Science, UCL)
Collaborators
- Prof. Prof. Cecilia Vindrola (UCL Division of Surgery & Interventional Sciences)
- Dr Tanzina Haque (Royal Free London NHS Foundation Trust)
- Dr Matthew Reeves (Institute of Immunity & Transplantation, UCL)
Funding
- Kidney Research UK
Human cytomegalovirus (HCMV), one of the most frequent infectious complications after kidney transplantation, can promote graft rejection and death. Natural killer (NK) cells countering HCMV are present in circulating blood and within donor kidneys. We aim to understand if kidney-resident NK cells can better control HCMV than circulating counterparts. We can then determine whether donor kidneys with high numbers of kidney-resident NK cells are better at controlling HCMV in recipients. Our work will ultimately help in the design of novel therapies against HCMV.
Lead Investigator
- Prof. Reza Motallebzadeh (Institute of Immunity & Transplantation / Division of Surgery & Interventional Science, UCL)
Collaborators
- 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)
Funding
- St Peter's Trust
- Kidney Research UK
- Rosetrees Trust
We are investigating if the presence of neutralising antibodies to interferon-alpha (IFNa) in patients with end-stage kidney disease alters humoral vaccine responses. Our work will form the basis of therapeutic strategies to improve specific SARS-CoV-2 antibody responsiveness by manipulation of cytokines such as IFN alpha in selected patients.
Lead Investigator
- Prof. Reza Motallebzadeh (Institute of Immunity & Transplantation / Division of Surgery & Interventional Science, UCL)
Collaborators
- Prof. Alan Salama (Department of Renal Medicine, UCL)
- Dr Douglas Fink (Institute of Immunity and Transplantation, UCL)
- Dr Rupert Beale (Francis Crick Institute)
- Dr Ed Carr (Department of Renal Medicine, UCL)
Funding
- Kidney Research UK
- St Peter's Trust
We are developing a novel point-of-care device to monitor urinary chemokines serially in renal transplant recipients and identify patients with incipient allograft injury. Immune-based biomarkers offer the potential for identifying patients at risk for graft rejection and for individualizing immunosuppression therapy.
Lead Investigator
- Prof. Reza Motallebzadeh (Institute of Immunity & Transplantation / Division of Surgery & Interventional Science, UCL)
Collaborators
- Prof. Manish Tiwari (Dept of Mechanical Engineering, UCL)
- Prof. Stavroula Balabani (Dept of Mechanical Engineering, UCL)
- Dr Mark Harber (Department of Renal Medicine, UCL)
- Dr Nick Salaris (Department of Mechanical Engineering, UCL)
- Dr Rohit Gupta (Department of Mechanical Engineering, UCL)
- Dr Arnab Guha (Department of Mechanical Engineering, Birla Institute of Technology & Science, India)
Funding
- Rosetrees Trust
- UCL Institute of Healthcare Engineering
- St Peter's Trust
Our aim is to develop a novel in vitro 3D human kidney organoid culture system to screen for compounds that can modulate fibrosis in chronic kidney disease.
Lead Investigator
- Prof. Reza Motallebzadeh (Institute of Immunity & Transplantation / Division of Surgery & Interventional Science, UCL)
Collaborators
- Prof. Jill Norman (UCL Centre for Experimental Nephrology)
- Prof. Krista Rombouts (UCL Institute for Liver and Digestive Health)
- Dr Giuseppe Mazza (Engitix Therapeutics)
- Dr Breda Twomey (UCB Pharma)
Funding
- UCB Pharma
We are developing a pipeline for automated, 3D histological review of pre-transplant deceased-donor kidney biopsies, powered by AI tools to replicate and ultimately augment human analyses. This work will facilitate optimization of donor organ quality assessment prior to transplantation, and unlock the promise of precision medicine for patients. Enhanced early detection methods and a sophisticated understanding of pre-clinical CKD could be more broadly applied to catalyze the development of novel, targeted therapeutic interventions with the potential to halt CKD progression.
Lead Investigator
- Prof. Reza Motallebzadeh (Institute of Immunity & Transplantation / Division of Surgery & Interventional Science, UCL)
Collaborators
- Prof. Ben Walsh (UCL Centre for Kidney and Bladder Health)
- Dr Keith Siew (UCL Centre for Kidney and Bladder Health)
- Dr Tobi Ayorinde (UCL Research Dept of Surgical Biotechnology)
- Dr Alastair Moss (AstraZeneca)
Funding
- AstraZeneca
- National Institute of Health Research
The cold and warm ischaemic injury inherent to deceased-donor kidney transplantation is associated with delayed graft function (DGF), referring to poor early graft function, and can lead to prolonged hospital stay, higher rates of acute and chronic rejection, and shortened mid/long-term allograft and patient. Proximal tubular epithelial cells undergo a metabolic switch from fatty acid oxidation to anaerobic glycolysis during ischaemia. This leads to the accumulation of intracellular free fatty acids (FFA) such as arachidonic acid, which can induce renal mitochondrial dysfunction and modulate TLR-dependent inflammatory cascades. Our work will use ultra-high performance, untargeted liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) of renal cortical biopsies from human donor kidneys to delineate FFA accumulation. By using an ex vivo machine perfusion model of kidney injury, we will investigate the effect of FFAs on the kidney, monitoring the effect this has an organ injury.
Lead Investigator
- Prof. Reza Motallebzadeh (Institute of Immunity & Transplantation, & Research Department of Surgical Biotechnology, UCL)
Collaborators
- Prof. Kevin Mills (Translational Mass Spectrometry Research Group, GOS Institute of Child Heath, UCL)
- Prof. Simon Eaton (GOS Institute of Child Heath, UCL)
- Dr Afolarin Otunla (UCL Research Dept of Surgical Biotechnology)
- Dr Joseph Shalhoub (UCL Research Dept of Surgical Biotechnology)
- Dr Kumaran Shanmugarajah (Massachusetts General Hospital, USA)
Funding
- Royal Free Charity
The thymus controls the development and function of T cells, a critical component of the adaptive immune system. We have identified and characterized bona fide self-renewing stem cells that are able to reconstitute a functional thymus ex vivo and in vivo. This system will allow us to investigate how tolerance of T cells to self-antigens is established in the thymus and also has potential therapeutic application in immune deficiencies. Establishing tolerance remains a holy grail of solid-organ transplantation, and thymic tissue carries with it the ability to induce tolerance to any other organ or tissue from the same donor (or another donor tissue-matched to the thymic tissue) if successfully transplanted. Our program, in collaboration with Prof Motallebzadeh, is developing a strategy for inducing kidney transplant tolerance by co-transplantation of bio-engineered thymic tissue.
Lead Investigator
- Prof. Paola Bonfanti (Institute of Immunity & Transplantation, UCL)
Collaborators
- Professor Reza Motallebzadeh
- Professor Francesco Leo (Uni Torino)
- Professor Sandro Olivo (UCL)
- Dr Charlotte Hagen (UCL)
- Professor Dominique Bonnet (Crick)
- Professor Adrian Hayday (Crick)
- Professor Francois Guillemot (Crick)
- Dr Alberto Elosegui-Artola (Crick)
- Dr Leanne Li (Crick)
- Dr Michele Mishto (KCL, Crick)
- Videregen
Funding
- European Research Council (ERC)
- The Rosetrees Trust
- Innovate UK
- London Advanced Therapies - Research England
- MRC Confidence in Concept UCL scheme
- MRC idea-2-innovate Crick scheme
- UKRI (ERC and MSCA Other Guarantee Calls)
- EC Marie Skłodowska Curie Individual Fellowship
- London Interdisciplinary Biosciences Consortium (BBSRC)
- ScienceCardCF Trust
- National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust.
Oesophageal atresia is a rare neonatal condition in which the upper part of the oesophagus does not connect with lower oesophagus and stomach. This is currently treated surgically by substitution with tissue from the stomach, colon or jejunum. We have been studying the different populations of stem cell and progenitor cells that maintain tissue homeostasis in the oesophagus. This work has shown that oesophageal epithelium can be used for autologous reconstitution of the oesophagus, which may be exploited therapeutically to promote oesophageal regeneration throughout life as an alternative or adjunct to surgery for treatment of oesophageal atresia.
Lead Investigator
- Prof. Paola Bonfanti (Institute of Immunity & Transplantation, UCL)
Funding
- Rosetrees Trust
- Duchenne Parent Project
- NIHR GOSH BRC
- GOSH Charity
Collaborators
- Prof. Francesca Ciccarelli (QMUL, Crick)
- Prof. Paolo De Coppi (UCL)
We aim to exploit the potential of basal airway epithelial cells to expand in culture and give rise to the other cell types that constitute the functional respiratory epithelium. We will use this platform to expand healthy as well as cells from cystic fibrosis patients before and after gene editing. Furthermore, we aim to rebuild ex vivo an organ-like structure that will mimic the 3D airways complexity for delivery of both cell and vectors to test cell/gene therapy ex vivo. We test new gene editing technology in airway stem cells, using a combination of liquid-air interface and microfluidic cultures that could pave the way for new therapies for cystic fibrosis.
Lead Investigator
- Prof. Paola Bonfanti (Institute of Immunity & Transplantation, UCL)
Collaborators
- Prof. Clare Jolly
- Prof. Robert Heyderman
- CF Trust SRC020 Consortium (UCL, St George Uni, Uni of Cork, Necker)
Funding
- Cystic Fibrosis Trust
- HIC-VAC
We are studying how stem cells / progenitor cells in the pancreas generate insulin-producing cells. In the long term, it is hoped that this knowledge might lead to the development of novel therapies for people with diabetes. In addition, knowledge acquired from our work on the thymus may lead to new therapies that tolerize the patient’s immune system to self insulin-producing beta cells.
Lead Investigator
- Prof. Paola Bonfanti (Institute of Immunity & Transplantation, UCL)
Collaborators
- Dr Rocio Sancho (KCL)
Funding
- The Rosetrees Trust
- National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust
Clinical Trials
A prospective multi-centre observational cohort study to determine whether ultrasound surveillance can reliably predict arteriovenous fistulae failure in patients with chronic kidney disease.
https://www.isrctn.com/ISRCTN36033877
A randomised controlled trial comparing clinical (one-year functional patency rate) and cost-effectiveness of regional versus local anaesthesia for primary arteriovenous fistula formation.
https://pubmed.ncbi.nlm.nih.gov/34937718
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.
https://www.nhsbt.nhs.uk/clinical-trials-unit/current-trials-and-studies/pithia/
This feasibility study aims to objectively detail how arteriovenous fistula (AVF) disconnection in renal transplant recipients can change cardiorespiratory fitness and physical capacity, potentially increasing patients' activity levels and improving quality of life.
https://doi.org/10.1186/ISRCTN49033491
This is a phase I, commercial study which aims to explore the safety and tolerability of autologous CAR-Treg in patients who have undergone liver transplantation. Long term this approach is hoped to enable withdrawal of immunosuppression treatments leading to a reduction treatment toxicity.
https://classic.clinicaltrials.gov/ct2/show/NCT05234190
UCL researchers secure £560m in ERC research funding
Paola Bonfanti's LOST IN ThyME project will explore the role of the thymus in the immune and endocrine systems.
Our experts
Renal Transplantation
Epithelial Cell Biology & Regenerative Medicine
Associate Professor
Funding and Partnerships
Selected publications
- Almotiri A, Boyd AS, Rodrigues NP (2023). Zeb1 Regulates the Function of Lympho-Myeloid Primed Progenitors after Transplantation. Biomolecules 13(9): 1386.
- Nag S and Boyd AS (2023). Decellularization of Mouse Kidneys to Generate an Extracellular Matrix Gel for Human Induced Pluripotent Sem Cell Derived Renal Organoids. Organoids. 2(1): 66-78.
- Roberton VH, Gregory HN, Angkawinitwong U, Mokrane O, Boyd AS, et al (2023). Local delivery of tacrolimus using electrospun poly-ε-caprolactone nanofibres suppresses the T-cell response to peripheral nerve allografts. J. Neural Engineering. 20: 016035.
- Forrest C, Chase TJG, Cuff AO, Maroulis D, Motallebzadeh R ... Reeves M (2023). Control of human cytomegalovirus replication by liver resident natural killer cells. Nat Commun. 2023; 14:1409.
- Ragazzini R, Boeing S, Zanieri L ... Bonfanti P (2023). Defining the identity and the niches of epithelial stem cells with highly pleiotropic multilineage potency in the human postnatal thymus. Developmental Cell, Vol. 58, Issue 22, 2428-2446.E9.
- Watson SA, Javanmardi Y, Zanieri L ... Bonfanti P, Moeendarbary E (2023). Integrated Role of Human Thymic Stromal Cells in Hematopoietic Stem Cell Extravasation. Bioengineering and Translational Medicine 2023 Mar; 8(2): e10454.
- Manook M, Motallebzadeh R, Pettigrew GJ (2022). Passenger donor lymphocytes: To affinity and beyond. Sci. Transl. Med 2022.
- Eleftheriadou D, Evans R, Atkinson E, Abdalla A, Gavins F, Boyd A, et al (2022). An alginate-based encapsulation system for delivery of therapeutic cells to the CNS. RSC Advances. 7 (12), 4005-4015.
- Almotiri A, Alzahrani H, Menendez-Gonzalez JB ... Boyd AS, et al (2021). ZEB1 modulates hematopoietic stem cell fates required for suppressing acute myeloid leukemia. J Clin Invest. 4;131(1).
- Carr EJ, Wu M, Harvey R ... Motallebzadeh R, et al (2021). Neutralising antibodies after COVID-19 vaccination in haemodialysis patients. Lancet 2021; 398:1038-1041.
- Muir L, Jaffer A, Rees-Spear C ... Motallebzadeh R (2021). Neutralizing antibody responses after SARS-CoV-2 infection in end-stage kidney disease and protection against reinfection. Kidney Int Rep, 2021; 6:1799-1809.
- Kreins AY, Bonfanti P, Davies EG (2021). Current and future therapeutic approaches for thymic stromal cell defects. Review. Frontiers in Immunology 2021 Mar 18;12: 655354.
- Park JE, Botting RA, Conde CD, Popescu DM, Lavaert M ... Bonfanti P, et al (2020). A cell atlas of human thymic development defines T cell repertoire formation. Science 2020 Feb 21;367 (6480).
- Meran L, Massie I ... Bonfanti P, et al (2020). Engineering transplantable mucosal grafts using primary jejunal organoids derived from children with intestinal failure. Nature Medicine 2020.
- Campinoti S, Gjinovci A, Ragazzini R ... Bonfanti P (2020). Reconstitution of a functional human thymus by postnatal progenitor cells and natural whole organ scaffolds. Nature Communications 2020, Dec 11: 632.
- Chhabra M, Alsughayyir J, Qureshi MS ... Motallebzadeh R, Pettigrew GJ (2019). Germinal Center Alloantibody Responses Mediate Progression of Chronic Allograft Injury. Front Immunol. 2019 Jan 23;9: 3038.
- Qureshi MS, Alsughayyir J, Chhabra M ... Motallebzadeh R, Pettigrew GJ (2019). Germinal center humoral autoimmunity independently mediates progression of allograft vasculopathy. J Autoimmun. 2019 Mar;98: 44-58.
- Harper IG, Gjorgjimajkoska O, Siu JHY ... Motallebzadeh R, Pettigrew GJ (2019). Prolongation of allograft survival by passenger donor regulatory T cells. Am J Transplant. 2019 May;19(5): 1371-1379.
- Qureshi MS, Alsughayyir J, Chhabra M ... Motallebzadeh R, Pettigrew GJ (2018). Data regarding transplant induced germinal center humoral autoimmunity. Data Brief. 2018 Dec 28;22: 647-657.
- Bonfanti P, Claudinot S, Amici AW, Farley A, Blackburn CC, Barrandon Y (2010). Microenvironmental reprogramming of thymic epithelial cells to skin multipotent stem cells. Nature. 2010 Aug 19;466(7309): 978-82.
Related courses
MSc Experimental & Translational Immunology
This MSc Experimental and Translational Immunology provides insight into state-of-the-art immunology research, current issues in immunity, immune dysfunction, and immune-based therapeutic approaches.
MRes Experimental & Translational Immunology
The MRes Experimental & Translational Immunology course covers basic science through to translational clinical research and culminates in a full-time research project in one of our laboratories.
PhD Infection & Immunity
An MPhil/PhD degree in Infection and Immunity offers an opportunity to work with world class scientists and to develop your skills as an independent researcher.
The role of intestinal barrier dysfunction & gut microbiota in acute renal transplant rejection
