Emerging diagnostic and treatment approaches in organ and stem cell transplantation

Lead Research Organisation: King's College London
Department Name: Medicine School Office

Abstract

Replacement of diseased organs and cells by healthy tissue is a dream that has partly been realised through progress in transplantation over the last 50 years. However, for transplantation therapy to achieve greater success and on a wider scale, advance is needed in several directions. These include finding supplementary sources of donor tissues and cells that lend themselves for therapy of a larger number of conditions, such as kidney and liver failure, arthritis, diabetes and tooth loss; and a way of ensuring acceptance of the replacement tissue without the need for lifelong drugs that block the immune system. To accelerate progress, experts in basic biology and transplant medicine at King s College London plan to come together in a joint venture with the Medical Research Council, to form the UK s first MRC Centre for Translation of Research in Transplantation. The Centre s mission is to put research in transplantation on a new trajectory to deliver more rapid and effective modes of diagnosis and treatment. The programme of research will apply extensive knowledge of human immunology, stem cell biology, genomics and imaging to develop new areas that will benefit human health. In collaboration with the King s College Centre of Medical Law and Ethics, the MRC Centre will also play a pivotal role in training and education.

Technical Summary

The immune system represents a formidable barrier to organ and cell transplantation adding to the problems caused by severe shortage of replacement tissues. We present a co-ordinated and integrated vision for how basic and clinical research can combine at a single centre to provide new diagnostic and therapeutic opportunities that can be applied to the alleviation of human suffering. The premise is that more specific manipulation of the inflammatory and immune systems will increase the number of donor organs that can be used for transplantation, will reduce the number of mid-term graft failures and will lead to minimisation or elimination of pan-immunosuppressive therapies, thus lowering the incidence of related malignancies. The proposed strategies include: (1) development and clinical trial of membrane targeted regulators of the complement and clotting cascades for the pre-treatment of donor organs; (2) investigation and development of clinical-grade cell based therapies to promote long-term graft acceptance without continuous immunosuppressive drugs; (3) development of new imaging methods for visualising and monitoring the activity of innate and adaptive immune systems, initially in pre-clinical models; (4) clinical and experimental evaluation of biomarkers that help to predict and interpret outcomes of transplantation; and (5) strategies for addressing the impact of the immune response in allogeneic stem cell based therapies. Outcome measures will take into account the rates of organ dysfunction due to ischaemia-reperfusion insult and acute rejection crises, annual graft survival rates, indices of chronic rejection, infection rates, clinical tools for measurement of tolerance, specificity and sensitivity of imaging procedures and predictive analysis in large, well-defined patient cohorts. The initial application and exploitation of the research results will take place in the fields of liver, kidney, bone marrow and stem cell-based repair/replacement of tooth and articular cartilage, and later will extend to other organs and tissues. The programme of studies within the Centre will provide a vibrant cross-disciplinary environment in which future leaders of research will acquire essential skills including the confidence to engage public interest in transplantation research and its benefits for patients.

Publications

10 25 50
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Abboudi H (2012) Decision making in urological surgery. in International urology and nephrology

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Ahmed K (2011) How to develop a simulation programme in urology. in BJU international

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Bartel G (2013) Donor specific transplant tolerance is dependent on complement receptors. in Transplant international : official journal of the European Society for Organ Transplantation

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Challacombe B (2011) Recognizing and managing the complications of prostate biopsy. in BJU international

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Challacombe B (2012) Focal HIFU for prostate cancer. in The Lancet. Oncology

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Choudhury SM (2011) Oncological outcomes of robot-assisted radical cystectomy. in BJU international

 
Description British Transplantation Society Living Donor Transplantation Guidelines
Geographic Reach National 
Policy Influence Type Membership of a guidance committee
 
Description MRC Centre for Transplantation Consultation Response to Academy of Medical Sciences Call for Evidence: Review of the Regulation and Governance of Medical Research
Geographic Reach National 
Policy Influence Type Membership of a guidance committee
Impact Expected to influence Goverment policy on: having a "single research regulator" with combined responsibility for different aspects of research regulation; the future of the National Research Ethics Service; and the reorganisation of the research regulatory activities of the Human Tissue Authority (which is directly relevant to transplantation).
 
Description MRC Centre for Transplantation Response to Nuffield Council on Bioethics Consultation paper Giver and Take? Human Bodies in Medicine and Research
Geographic Reach National 
Policy Influence Type Membership of a guidance committee
Impact The evidence gathered in this consultation is likely to affect Government policy on developing a single regulatory authority to consider multiple aspects of medical research. This is likely to have an impact on policy and legislation in organ donation and transplantation.
 
Description Organ Donation Taskforce Ethics Working Group
Geographic Reach National 
Policy Influence Type Membership of a guidance committee
Impact The specific remit of this working group was to consider the potential impact of an 'opt-out' system of organ donation in the UK. The working group reported to the Department of Health.
 
Description Technology Strategy Board Assessor Briefing for Healthcare
Geographic Reach National 
Policy Influence Type Participation in advisory committee
 
Description British Transplant Society Fellowship Award
Amount £40,000 (GBP)
Organisation British Transplantation Society (BTS) 
Sector Learned Society
Country United Kingdom
Start 09/2008 
End 10/2009
 
Description Guy's & St Thomas' Charity - New Services and Innovations Grant
Amount £20,000 (GBP)
Organisation Guy’s & St Thomas’ Charity 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2010 
End 01/2011
 
Description MRC Centenary Event award
Amount £30,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 09/2012 
End 06/2013
 
Description MRC Centenary award
Amount £45,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 06/2012 
End 05/2013
 
Description MRC Centre Grant
Amount £2,700,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 09/2007 
End 09/2012
 
Description MRC Centre Grant (Directors Initiative)
Amount £250,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2007 
End 09/2012
 
Description MRC Developmental Clinical Study
Amount £1,727,417 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 08/2011 
End 06/2014
 
Description MRC Director's Initiative
Amount £203,088 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 09/2007 
End 08/2012
 
Description MRC PhD Studentship
Amount £50,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2007 
End 09/2010
 
Description MRC Project Grant
Amount £520,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 12/2007 
End 12/2010
 
Description MRC Project Grant
Amount £600,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2008 
End 09/2011
 
Description MRC Public Engagement Grant
Amount £10,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 08/2010 
End 10/2010
 
Description NIHR Biomedical Center Grant
Amount £5,369,000 (GBP)
Organisation National Institute for Health Research 
Department NIHR Comprehensive Biomedical Research Centre, Guy's and St Thomas
Sector Public
Country United Kingdom
Start 04/2007 
End 03/2012
 
Description NIHR Senior Investigator award
Amount £40,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 05/2008 
End 04/2012
 
Description Public Engagement
Amount £10,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 08/2010 
End 01/2011
 
Description Wellcome Trust Equipment Grant
Amount £977,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2007 
End 08/2010
 
Description Wellcome Trust Project Grant
Amount £222,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2006 
End 01/2009
 
Title Complement imaging technology 
Description Cloning of complement receptor 2 and modification to develop a new imaging tool for detection of complement activation by external body imaging. 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact Work in progress. 
 
Title Complement imaging technology 
Description Cloning of complement receptor 2 and modification to develop a new imaging tool for detection of complement activation by external body imaging. 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact Work in progress. 
 
Title Core administrative and laboratory facilities 
Description 1.Refurbishment of office and laboratory space including new human protein therapeutics laboratory to accommodate Centre activities, including new activities. 2.New administrative/research structure for the MRC Centre including Centre Manager, administrative assistant, statistical support and microsurgical team. 
Type Of Material Improvements to research infrastructure 
Year Produced 2007 
Provided To Others? Yes  
Impact 1.Facilitated several major grant awards, as listed. 2.Developed a dedicated Centre website with strongly positive feedback 3.Increased media profile, as listed 4.Dissemination through workshops and meetings as listed and selection for the British Science Festival 2010. 
 
Title Quantitative PCR 
Description Through the Centre collaboration with Genetics, we have established rigorous quantitative expression methods on transplant samples in liver and kidney recipients. 
Type Of Material Data analysis technique 
Provided To Others? No  
Impact Work in progress 
 
Description AdProTec, UK 
Organisation AdProTec
Country United Kingdom 
Sector Private 
PI Contribution 1.Established the rationale of membrane targetting approach to prevent complement injury in donor kidney organs. 2. Enabled pre clinical study in prevention of reperfusion damage. 3. Enabled and led clinical (phase IIa) study to determine safety and feasibility of treating donor organs prior to transplantation.
Collaborator Contribution The company provided chemicals and consumables for this study
Impact Publications - Pubmed references 14507653 and 16510763 Joint patent application (Case 40336). This is now wholly owned by King's College London. Led to development of PhD project successfully awarded in 2006. Keynote symposium presentations including Presidents Lecture, Transplantation Society for Australia and New Zealand 2007.
 
Description Alexion Pharmaceuticals 
Organisation Alexion Pharmaceuticals
Country United States 
Sector Private 
PI Contribution We collaborated on an investigator led pre clinical study to determine the impact of complement inhibitor (anti-C5) on reperfusion injury in native and transplant kidneys.
Collaborator Contribution Alexion Pharmaveuticals provided Chemicals, Consumables and animals to this study
Impact The therapeutic antibody failed to penetrate into transplanted kidney and therefore helped to define types of injury that would not amenable to this particular therapeutic strategy.
 
Description Complement UK 
Organisation Cardiff University
Department Infection and Immunity
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation Great North Children's Hospital (GNCH)
Department Pediatric Nephrology
Country United Kingdom 
Sector Hospitals 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation Imperial College London
Department Faculty of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation Leeds Teaching Hospitals NHS Trust
Department Department of Clinical Haematology
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation Manchester University NHS Foundation Trust
Department Nephrology and Transplantation
Country United Kingdom 
Sector Hospitals 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation Medical Research Council (MRC)
Department MRC Human Genetics Unit
Country United Kingdom 
Sector Public 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation Newcastle University
Department Institute of Cellular Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation Newcastle University
Department Institute of Human Genetics
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation University College London
Department Institute of Neurology
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation University College London
Department Institute of Ophthalmology UCL
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation University College London
Department Research Department of Epidemiology and Public Health
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation University College London
Department Structural Molecular Biology
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation University of Bath
Department Department of Biology and Biochemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation University of Bristol
Department School of Cellular and Molecular Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation University of Cambridge
Department Department of Clinical Biochemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation University of East Anglia
Department School of Medicine UEA
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation University of Edinburgh
Department School of Biological Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation University of Edinburgh
Department School of Chemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation University of Leicester
Department Department of Infection, Immunity and Inflammation
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation University of Leicester
Department Department of Molecular and Cell Biology
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation University of Oxford
Department Sir William Dunn School of Pathology
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation University of Southampton
Department School of Medicine Southampton
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Complement UK 
Organisation University of Warwick
Department Warwick Medical School
Country United Kingdom 
Sector Academic/University 
PI Contribution Initiated formation of Complement UK in conjunction with Prof Paul Morgan (Cardiff University). Developed a research and training strategy.
Collaborator Contribution The partners consist of over 30 PIs at over 20 Centres in the UK. They have contributed through an Executive Committee to the strategy development and implementation. In particular they have helped run annual events and studentship funding.
Impact Alexion funded four year PhD Studentships x 4 First annual conference 2011; repeated 2012, 2013. Special Editions of the Journal of Immunobiology (November 2012); (2013 in prep)
Start Year 2009
 
Description Harvard University 
Organisation Harvard University
Department Harvard Medical School
Country United States 
Sector Academic/University 
PI Contribution We have built a research collaboration on biomarkers in transplantation with Professor Terry Strom, by giving him access to patients and testing his samples in the kidney transplant unit. We have jointly written grant awards (L. Barber and S. Longi) and we have jointly funded a joint postdoctoral researcher to look at tissue stress factors in transplantation. In addition, we have set up teaching sessions to introduce research opportunities from Harvard University and we have set up a major international symposium (GMEC Genetics Symposium, November 2009) which featured his work.
Collaborator Contribution We have access to confidential information and primer sequences that define potential biomarkers currently under investigation in our Centre as a result. It has facilitated recruitment of a new Professor to the MRC Centre from the USA.
Impact 1. Organising GMEC Genetics Symposium (2009) 2. Organising workshops 3. Putting in two grant applications 4. Partnership with Quest (negotiation stage)
Start Year 2007
 
Description Lombardi-Mullen 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution regulatory T cell expertise and models of skin transplantation
Collaborator Contribution expertise in full body imaging
Impact 2 publications already in pub med and 3 more in preparation
Start Year 2008
 
Description Lombardi-Nestle 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution regulatory T cell expertise and knowledge in the mechanisms of tolerance
Collaborator Contribution establishing in vivo model of human skin transplantation
Impact See publications - PubMed ID 22937164 & J.Exp.Med.209(5) 935-945; Ali et al. Plos ONE (In Press)
Start Year 2008
 
Description Requirement of complement C3 for transplant tolerance induction 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Led to the initial observation that C3 deficient mice were resistant to tolerance induction.
Collaborator Contribution Provided a Clinical Fellow with an interest in complement and transplantation. This has enabled a new scientific question to be addressed.
Impact The initial results showing the requirement for C3 in tolerance to skin grafts was presented at an international meeting.
Start Year 2008
 
Description University of Pittsburgh - Immunology Department 
Organisation University of Pittsburgh
Department Department of Pharmaceutical Sciences
Country United States 
Sector Academic/University 
PI Contribution We provided the expertise, laboratory equipment and facilities and intellectual input into this project. The work was partly funded by NIH grant.
Collaborator Contribution Contributed one year of work in our laboratory for a self funded PhD student.
Impact 1. Imperial College PhD award for Chih Che Li 2. Publications: a. Pubmed ID: 19000927 b. Pubmed ID: 18791452
Start Year 2007
 
Description Wellcome Trust Case Control Consortium 3 
Organisation The Wellcome Trust Sanger Institute
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Graham Lord and co-applicants in the MRC Centre put together a transplant GWAS proposal, which led to a network of 22 transplant centres in the UK and Ireland who will contribute donor and recipient DNA.
Collaborator Contribution funding and SNP analysis
Impact A pilot genome study involving around 600 donor-recipient pairs at Guy's Hospital has been completed. Publication on Complement genes submitted.
Start Year 2009
 
Description Yale University 
Organisation Yale University
Country United States 
Sector Academic/University 
PI Contribution Development of collaborative research programme
Collaborator Contribution Development of collaborative programme
Impact Publication available in e Print. Author Prof Adrian Hayday. Journal of Investigative Dermatology 2009. Study of T cells that promote tissue growth and wound repair.
Start Year 2007
 
Title Anticomplement Compounds 
Description Recovery of IP and materials related to membrane-localising ("cytotopic") technology discovered by our lead protein chemist and head of Protein Therapeutics Laboratory (before joining our Centre). 
IP Reference US7888318 
Protection Patent granted
Year Protection Granted 2011
Licensed Commercial In Confidence
Impact Return of the IP will enable new grant proposals and the conduct of a Phase IIB efficacy study in transplant patients.
 
Title Antithrombotic Compounds 
Description It has been found that linkage of anticoagulant peptides to membrane-localising ("cytotopic") reagents generates conjugates which are capable of inhibiting thrombin when attached to cell surfaces. This enables organs to be anticoagulated by perfusion ex-vivo prior to transplantation into the recipient. For the first time, it appears to be possible to separate local antithrombotic effects from systemic pharmacological ones using a readily translatable therapeutic agent. 
IP Reference WO2011027175 
Protection Patent granted
Year Protection Granted 2011
Licensed No
Impact It may be possible to control thrombosis in transplantation (for example, in pancreatic and islet cell transplantation and in the prevention of antibody-mediated acute rejection) using this approach, as shown in early pre-clinical models in rat.
 
Title Antithrombotic agent (PTL004) 
Description It has been found that linkage of anticoagulant peptides to membrane-localising ("cytotopic") reagents generates conjugates which are capable of inhibiting thrombin when attached to cell surfaces. This enables organs to be anticoagulated by perfusion ex-vivo prior to transplantation into the recipient. For the first time, it appears to be possible to separate local antithrombotic effects from systemic pharmacological ones using a readily translatable therapeutic agent. It may be possible to control thrombosis in transplantation (for example, in pancreatic and islet cell transplantation and in the prevention of antibody-mediated acute rejection) using this approach. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Initial development
Year Development Stage Completed 2009
Development Status Under active development/distribution
Impact First product of its kind enabling prevention of Thrombosis in an organ transplant without having to anti-coagulate the recipient. Potential use in organs transplanted into pre-sensitised recipients. 
 
Title Cytotopic human interleukin 15 
Description Modified human cytokine designed to generate regioselective immune stimulation within human tumours. Principle source of funding: Prostate Cancer UK/Heathside Fund 
Type Therapeutic Intervention - Drug
Current Stage Of Development Initial development
Year Development Stage Completed 2012
Development Status Under active development/distribution
Impact N/A 
 
Title Empirikal-Mirococept 
Description Membrane - interactive complement inhibitor used by ex vivo perfusion into isolated organ. About to enter definitive Phase II study. Drug manufacture completed to accepted standard. MHRA approved. Patient recruitment imminent. Souce of funding: MRC DCS grant. Recruitment began in July 2015 and 19 patients are now undergoing treatment. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2006
Development Status Under active development/distribution
Clinical Trial? Yes
Impact Validation of the membrane-binding (cytotopic) approach used in Mirococept and the consequent development of this technology as a platform. Large scale manufacture and quality assessment for clinical trial completed. Completed investigators brochure. Ethics approved. MHRA approved. Patient recruitment open. 
URL http://www.mykidney.org/Research/ResearchAtGuys.aspx
 
Title Membrane targeted anti-thrombin PTL006 
Description A membrane targeted anti-coagulant for intented use in donor kidneys transplanted into high risk (highly sensitised) recipients. Currently at proof-of-principle stage in rat model. Current funding - MRC Centre Grant Directors Initiative. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2010
Development Status Under active development/distribution
Impact Patent application registered. 
 
Description Associate Parliamentary Committee for Surgical Services 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Advised House of Lords on the need for simulation for patient safety, European Working Time Directive, Emergency Surgery

Awaiting outcomes
Year(s) Of Engagement Activity 2012
 
Description Away Day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Primary Audience Participants in your research and patient groups
Results and Impact A meeting to engage clinicians in the scientific programme of the Centre and vice versa, and to promote patient-involvement in the Centre's mission, through breakout sessions, some of which were patient-led.

A collaborative grant proposal has been submitted to the NIHR; progress with Transplant Biobank across the Centre; KPA involvement in the planning of the Bristish Science Festival; increased coverage in KPA newsletters; started monthly educational sessions with patients.
Year(s) Of Engagement Activity 2010
 
Description Away Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Primary Audience Health professionals
Results and Impact Over 70 delegates from across the Centre and beyond enjoyed a full programme of events including presentations from Dr Varuna Aluvihare and Professor Steven Sacks; a series of talks on current areas of clinical translational research and a lively debate on some of the major issues facing the Centre. Issues discussed included defining priority areas for clinical/academic research and the Centre's promotion of clinical engagement. Professor Andrew Bradley from Cambridge University delivered some provocative insights in his keynote speech, outlining possible future challenges to the Centre.

That the away day attracted such a diverse audience only added to its success. Some excellent ideas emerged at the event, such as developing supported mentorship for staff and creating opportunities for clinicians to shadow lab staff and vice versa. Also suggested was a Centre discussion board for staff from all areas to share ideas in an easy to use forum.
Year(s) Of Engagement Activity 2009
 
Description BBC R4 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Recorded broadcast on national radio on the ethics of transplantation as part of the BBCR4 science series Inside the Ethics Committee
Year(s) Of Engagement Activity 2012
 
Description BBC Radio 4 Interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact Prof Steven Sacks describes his work on finding an easier way to get the body to accept a new organ on BBC Radio 4.

Publicity for the work of the MRC Centre for Transplantation.
Year(s) Of Engagement Activity 2008
 
Description BBC Radio 4 Interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact Prof Steven Sacks describes his work on finding an easier way to get the body to accept a new organ on BBC Radio 4.

Publicity for the MRC Centre for Transplantation.
Year(s) Of Engagement Activity 2008
 
Description BBC Radio 4 Interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact BBC Radio 4 invited Professor Steven Sacks to talk about a new technique that would extend the life of a kidney transplant significantly.

The story received media attention and was later supported by the successful application of an award to help with first in man clinical trials.
Year(s) Of Engagement Activity 2010
 
Description BBC Radio 4 interview 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact Prof Steven Sacks describes his work on finding an easier way to get the body to accept a new organ at the MRC Centre for Transplantation, on BBC Radio 4.

Gain exposure of the MRC Centre for Transplantation.
Year(s) Of Engagement Activity 2008
 
Description Ethics Symposium 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Primary Audience Health professionals
Results and Impact The MRC Centre for Transplantation held an ethics workshop entitled 'on the possibility of translation'. The workshop was attended by ethicists, lawyers, scientists, social scientists and clinicians.

At the end of the meeting the group made two proposals. First, that a one day seminar be held to address the problem of nomenclature and regulatory processes in the context of translational research. Second, that a Health Services Research Fellow (a post doctoral social scientist) be appointed to address generally how innovative research methods are conceived by patients, clinicians, scientific researchers, and organ donors, and to address more specifically issues relating to biomarker studies and clinical transplantation. This appointment is now underway.
Year(s) Of Engagement Activity 2009
 
Description Extending the Life of the Transplant 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Primary Audience Public/other audiences
Results and Impact The meeting will bring members of the public face to face with researchers, clinicians and patients dealing with the early failure of transplants and discuss how scientific advance is envisaged to overcome these challenges. Presentations will be aimed at a lay audience, in particular school children who will engage in ethics debate.

Intended to raise public awareness of the scientific contribution to transplantation and increase interest in the organ donor registry.
Year(s) Of Engagement Activity 2010
 
Description GMEC Genetics Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Primary Audience Participants in your research and patient groups
Results and Impact The workshop brought together a group of experts and potential collaborators who expressed interest in trying to understand how genetic variation influences the results of transplantation and how this can help to personalise anti-rejection therapy and improve outcomes.

The workshop increased awareness of the need for collaboration between UK centres in achieving the goals. It has also resulted in a newsletter on the GMEC and KCL websites, which raised the profile of the necessary work. The presence of a Nature editor at the meeting also raised the possibility of future dissemination.
Year(s) Of Engagement Activity 2009
 
Description Genomic subpopulations and health systems responses 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? Yes
Primary Audience Participants in your research and patient groups
Results and Impact A workshop to examine developments in genomic subclassification and the impact this is likely to have on health system responses. Emphasis on how advances in genetic immunotyping may change or challenge organ donation and transplantation practice.

Greater involvement and understanding of the Centre's work by academics from allied disciplines..
Year(s) Of Engagement Activity 2010
 
Description KPA Newsletter - The RituxiCAN-C4 trial 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? Yes
Primary Audience Public/other audiences
Results and Impact Following the talk to the KPA, Professor Dorling was requested to provide a brief overview of his clinical research for the KPA newsletter which was published in May 2010

This was distributed across all dialysis and transplant sites for all the renal patients to see.
Year(s) Of Engagement Activity 2010
 
Description KPA Open Day - How and why we do research on tolerence in kidney transplant patients 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Participants in your research and patient groups
Results and Impact Dr Maria Hernandez-Fuentes explained to patient groups why we do research in biomarkers in tolerence for kidney transplant patients and what are the outcomes so far.

The study was mentioned in the national press when it was published in June and other electronic sources in of general science. The importance was given to the fact that we could be eventually able to identify a small groups of patients that may not need as much immunosuppression as it is used now.
Year(s) Of Engagement Activity 2010
 
Description KPA Open Day - The RituxiCAN-C4 trial 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Health professionals
Results and Impact Professor Anthony Dorling gave an overview of the problem called chronic rejection - the fact that kidney transplants fail prematurely, and outlined the research ongoing to try and address this problem, focusing on the study he has been running, called 'RituxiCAN-C4'

Professor Dorling supplied a brief overview of the trial for the KPA newsletter, which was published at the end of May.  
Year(s) Of Engagement Activity 2010
 
Description Kidney Patient's Association Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Primary Audience Participants in your research and patient groups
Results and Impact Laboratory visit and talk concerning ongoing research.

Articles in National KPA Newsletter
Year(s) Of Engagement Activity 2009
 
Description Kidney Patients Association Board Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Primary Audience Participants in your research and patient groups
Results and Impact Summary of translational research including progress with complement inhibitors and potential therapeutics.

Ongoing funding notably £750K contribution to the MRC Centre for Transplantation.
Year(s) Of Engagement Activity 2007
 
Description Kidney Patients Association Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Primary Audience Health professionals
Results and Impact On Saturday 28th February the MRC Centre threw open its doors to the local KPA, their family and friends. Visitors were treated to a tour of the labs, where staff demonstrated some of the current research techniques and highlighted some of the new initiatives.

It was a great opportunity for those affected by kidney disease to learn about the future direction of their treatment. "It is amazing what [they] are doing" said Mr Ron Brooker, one of the visitors. "I enjoyed meeting the people involved...and what wonderful machines!". The lab staff also appreciated meeting the people who will directly benefit from their work.
Year(s) Of Engagement Activity 2009
 
Description Kidney Patients' Association Open Day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Primary Audience Participants in your research and patient groups
Results and Impact Laboratory visit and talk concerning ongoing research.

Articles in National KPA newsletter.
Year(s) Of Engagement Activity 2009
 
Description NICE expert panel 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Health professionals
Results and Impact LUTS and incontinence guidelines.

The role of Role of Botulinum Toxin-A was presented to NICE for due consideration
Year(s) Of Engagement Activity 2012
 
Description PEOPLE Magazine 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? Yes
Primary Audience Public/other audiences
Results and Impact Article entitled: "Improving transplant sucess".

Exposure of the MRC Centre and its work to wides community and Health professionals within the Trust.
Year(s) Of Engagement Activity 2009
 
Description Patient Involvement talks- KPA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact Monthly meetings between research staff and kidney patients to explain the research that is taking place in the Centre.

Greater patient involvement and understanding of the Centre's work.
Year(s) Of Engagement Activity 2010
 
Description Session Organiser for BSI 2013 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact None as yet - Meeting occurring 2-5 December 2013
Year(s) Of Engagement Activity 2013
URL http://www.bsicongress.com/
 
Description Social Mobility Foundation Inernship programme 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Schools
Results and Impact The Social Mobility Foundation is organising Internship Programmes every year and the MRC Centre offered to be involved,

quote from one of our interns "I just wanted to say a quick thank you as the internship was very useful as it has undoubtedly heightened my understanding of the career path that I am considering. Not only has it allowed me to expand my knowledge beyond the curriculum but it has also boosted my confidence and interpersonal skills.

Thank you very much for such a great opportunity."
This student is about to start her final year and pass her A levels and move on to a science higher degree.
Year(s) Of Engagement Activity 2010,2011,2012,2013,2014
URL http://www.socialmobility.org.uk/
 
Description TIME magazine 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact Prof Steven Sacks was interviewd by TIME magazine and his views were incorporated into the article "In Spain, a transplant that rules out rejection" by Claudia Castillo (November 2008)

The MRC Centre for Transplantation has been presented in a wide range of audience in USA.
Year(s) Of Engagement Activity 2008
 
Description The ethics of organ retrieval: goals, rights and responsibilities 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Health professionals
Results and Impact This was a unique forum bringing together clinicians, academic lawyers, ethicists, policy makers, key stakeholders and members of the public, concerned with organ donation and transplantation. The discussion focused on ethical issues regarding organ retrieval and its impact on transplant services and outcome.

Informed policy development on: a. required referral for brainstem death testing and organ donation on the basis of clinical triggers'; b. Donor organ optimisation. Led to a special issue of the Journal Clinical Ethics ""The ethics of organ retrieval' which will examine empirical ethics, law and public policy.
Year(s) Of Engagement Activity 2010