Announcements

Driving Discoveries – Accelerating Research blog by Maria Kaisar, Associate Professor of Transplantation Science, University of Oxford and QUOD Basic Science Coordinator

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Kidney Research UK’s annual research conference, Driving Discoveries – Accelerating Research, has evolved to be one of the highlights in our scientific diaries. This year’s conference was no exception, in that it was an excellent congregation of scientists and early career researchers who showcased the ongoing novel and impactful scientific work in kidney disease, funded by Kidney Research UK.  This year’s conference also introduced a new initiative where each session was chaired by an academic and a patient, so Professor Claire Sharpe and patient co-chair, Ifrah Raza chaired the opening session ‘Making discoveries count: the pathway to patients’ in which I had been invited, alongside Professor Nick Selby, to give a talk.

My talk ‘Improving donor kidney assessment developing new therapies so transplants last for longer’ covered research updates on our two research projects funded by KRUK, known as ADMIRE ‘Assessing Donor Kidneys and Monitoring Transplant REcipients and REDEEM ‘REnal Degradomics – Examining Donor Kidney Extracellular Matrices’. I took this opportunity to describe our research on developing better markers to assess donor kidneys. Analysis of a large number of QUOD samples and the application of machine learning approaches shows that we can develop more accurate methods to assess donor organs so only the organs that will function well are transplanted. I was also very happy to show our data on better understanding the biological processes of kidney injury and repair and how we could use targeted therapies to either protect donor organs from further injury during donor management or during preservation. I also presented our collaborative work on the potential use of MRI to assess donor organs and monitor transplant recipients led by Professor Sue Francis at Nottingham University, who was also one of the attendees.

Since members from my team also attended the conference, we had opportunities to socialise and meet other researchers at the poster sessions and over dinner. The Driving Discoveries – Accelerating Research meeting brings the kidney research community together to share their knowledge and speak about the work they are doing to improve the lives of kidney patients, so I am looking forward to next year’s highlights already!

Research Highlight: SIGNET

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RAP100: Examining the mechanisms involved in the potential down-regulation of brain-stem death induced proinflammatory responses by simvastatin

This project builds on an NIHR-funded HTA trial, SIGNET, a study randomising organ donors to statin treatment or control. The trial started in September 2021 and is the largest organ donor intervention study anywhere in the world. The mechanistic arm, the subject of this study, is NIHR-EME funded and utilises the QUOD biobank to access to samples from organ donors in the study. This study is led by Professors Simi Ali and John Dark at Newcastle University.

Statins are 3-hydroxy-3-methyl coenzyme A reductase inhibitors, with many pleiotropic effects, which may modulate the inflammatory processes in brain-stem dead donors. The hypothesis is that a statin within protocolised care after diagnosis of brain-stem death improves outcomes in patients undergoing transplantation. The study aims to explore the underlying mechanistic pathways that confer statin induced organ protection.

Main objectives are:

  1. Examine whether statin administration reduces donor inflammation by cytokine modulation and if time of administration has an effect.
  2. Determine whether inflammatory sub-phenotypes exist in the donor population and whether these sub-phenotypes are associated with clinical outcomes (number of organs utilised per donor)
  3. Examine gene expression profiles in heart tissue biopsies after donor statin administration.
  4. Examine long-term effects of statin treatment in a selected cohort of transplant patients.

Experiments are being carried out with data already collected in the National Transplant Database and biological samples from the QUOD programme. No extra data or blood samples are needed from recipients/donors.

Serum samples are obtained before the drug is administered, but after brain death, and then at organ retrieval from donors in both arms of the study. These samples are being tested for cytokines, to detect whether there is a significant difference in cytokine expression between the treatment groups and to study the effect of time of administration on statin-induced cytokine changes. Secondly, these cytokine data along with baseline data will be used in a latent class analysis (LCA), without consideration to outcome, to identify donor sub-phenotypes. Post-LCA discovery, we will study whether sub-phenotypes correlate with distinct clinical outcomes.

In order to identify genes, which are involved in statin induced anti-inflammatory effects, the tissue samples from donors which show anti-inflammatory response will be used to identify the differentially regulated genes in pairwise comparisons. Finally, in order to evaluate whether initial statin administration has long term anti-inflammatory effects in patients, analysis will be carried out in a smaller cohort of local transplant patients.

This will potentially allow us to identify organ donors based on cytokine and gene expression who are more likely to benefit from statin intervention. Thus, leading to larger organ pool and better function in recipients.

QUOD Whole Organ programme

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Following the successful implementation of the QUOD Whole Organ Programme in 2018, in which whole organs not suitable for transplant but with consent for research can be accepted for use in QUOD research projects, we have now also established a Transplant Technician (TT) service to support and facilitate the programme. This consists of a group of enthusiastic individuals providing an on-call service for whole organ research offers. The role involves reviewing any organs offered for research and determining whether they meet the specifications of any of the active research projects approved by the QUOD Steering Committee and signed off by ROFG (formerly RINTAG). If the organs are suitable, the TT notifies the researcher that they have accepted an organ for their project and arranges for the organ to be transported to the appropriate location. The TT service includes out-of-hours and weekend cover and is designed to support researchers so they do not need to be available 24 hours a day, 7 days a week.

The TT team comprises individuals who are interested in supporting science and research. Being part of the team is an excellent way to meet new people, develop contacts in the field of transplantation, boost income, and make a difference.

The QUOD whole organ service is available to researchers located anywhere in the UK and provides an infrastructure to support researchers and their projects, whilst helping to improve utilisation of whole organs offered for research use. QUOD also offers bespoke sample collection from whole organs, with researchers able to request samples tailored to their own requirements from heart, kidney, and pancreas. Details of the research projects QUOD has supported via the whole organ service can be found on our website Approved Research Projects – QUOD (please refer to the following projects: RAP069, RAP083, RAP091, RAP094, and RAP097).

If you are interested in accessing whole organs or being part of this programme, please contact us for further details. 

Please note: This service does not have any role in ranking and organ allocation to specific projects. 

Work experience students visit to the QUOD hub lab

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In July 2024, QUOD teamed up with the Transplant Research Group at the University of Oxford to welcome students visiting as part of the Nuffield Department of Surgical Sciences Work Experience Programme. This annual programme offers school students aged ≥16 years a unique opportunity to gain valuable insight into careers in science and medicine, including time in the laboratory, shadowing clinicians and research nurses, a careers talk, and a feedback session.

It was a privilege to host the students for two afternoons. During their time with us, they learned about how QUOD samples are collected from organ donors at the 61 participating hospitals across the UK and then shipped to the QUOD hub in Oxford, where they are then processed and stored in the biobank. The students learned about the importance of the Human Tissue Act 2004 and were shown a video explaining the journey of a QUOD sample, from obtaining consent from the donor families to sample collection and storage in the biobank, as well as the types of research QUOD supports. They were then given a tour of our laboratory, where they watched a demonstration of how the samples that come to the Oxford hub are processed for long-term storage and how some of the tissue biopsies are processed as formalin-fixed paraffin-embedded blocks and subsequently sectioned using a microtome to prepare slides that go on to be used for histological analysis. The students also spent time with Dr Letizia Lo Faro from the Transplant Research Group, who uses QUOD samples in her research. They were given the opportunity to look at slides containing samples from different tissues (such as kidney, heart, and liver) under the microscope, see the types of equipment used for organ perfusion experiments, and gain hands-on experience practising their pipetting skills.

We wish the students every success for the future, whatever they go on to do, and hope that this experience has inspired them.

QUOD at TTS 2024

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In September, QUOD travelled to Istanbul, Turkey, to attend The Transplantation Society 2024 (TTS2024) Congress. This was the first time that QUOD had participated at the biennial event, which enabled us to connect with a huge number of transplant professionals from across the world. It was a wonderful opportunity to catch up with QUOD colleagues as well as researchers who had used QUOD previously and were attending the congress. We had a lot of visitors and interest in our exhibition stand and we were able to promote the bioresource to a wide audience.

The TTS2024 programme was jam packed, with a wealth of novel research and new ideas being presented, sparking stimulating discussions. We were excited to see research using QUOD samples featured in an e-poster from Hussain Abbas. QUOD supplied samples from >1,000 liver donors to this study, which revealed differences between DBD and DCD donors and highlighted the under-utilisation of DCD livers as well as preretrieval biochemical and metabolic derangements that contribute to the risk factors associated with DCD livers.

TTS2024 was a huge success and opened up the opportunity to connect and showcase QUOD internationally.

Spotlight on a QUOD colleague – Karen Rockell

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For this issue of the QUOD newsletter, we caught up with Karen Rockell, Patient Co-Director of the UK Organ Donation and Transplantation Research Network (UKODTRN) and member of the QUOD Steering Committee.

Karen’s story of how she became involved with patient and public involvement and engagement (PPIE) in transplant research stemmed from her own first-hand experience as an organ recipient. Karen’s professional life began in business research, and she developed a wealth of knowledge working at Cranfield University for 10 years. However, her career took a different path when, in 2010, she became a liver transplant recipient, which prompted her to turn her focus towards health research. She recalled how she had always been interested in health research from an early age when her mother became a research participant for studies into a condition that she suffered from. Later, when Karen was diagnosed with an autoimmune condition, her interest in patient involvement in medical research was rekindled as she wanted to better understand her illness, explore possible new treatments, and be able to advocate for herself. After her transplant, she donated her “old” liver for research and, following her recovery, went on to join the NHS Blood and Transplant (NHSBT) public advisory group, thus beginning her journey in patient involvement in research.

Karen is Patient Co-Director of the UKODTRN, whose founding partners include NHSBT, the British Transplantation Society, and Kidney Research UK, who currently fund the network. The UKODTRN was initially set up to tackle some of the challenges presented by small, single-centre research that ultimately delay the time taken to generate results and increase knowledge. The UKODTRN aims to encourage collaboration and communication between researchers and support them to join forces and submit research applications as multicentre studies, which can generate larger datasets and overcome the geographical and other barriers that may prove problematic for single-centre studies. The UKODTRN sets out to involve patients right from the very beginning of the research, and the election of two co-directors, one clinician (Dr Adnan Sharif) and one patient (Karen Rockell), ensures a balance between and combines these two different but very relevant backgrounds. Karen’s role is to build the patient involvement group (PPIE), which now has around 160 members. The PPIE group includes waiting list and transplant patients, living donors, and donor families, as well as carers and families. There are also 140 clinicians, allied health professionals, scientists, research designers, and health economists.

The UKODTRN is currently focusing on two main projects, both of which are patient-driven and patient-centred. The first aims to identify research priorities and involves asking transplant patients and their carers what they think would improve patient outcomes. Once emerging themes have been identified, they will communicate with scientists to establish how to ask the right research questions to address these issues. The second project aims to demystify research, with the objective of developing a research-knowledge community to create plain-language summaries of research published within the past couple of years. These summaries will be written by patients, as those written by researchers may not be fully accessible to patients. These will take the form of written summaries, infographics, posters, leaflets, webinars, and podcasts to ensure that accessibility needs are met and the research is brought to patients in a really relatable way. The intention is to close the knowledge gap in order to share science with patients in a way that enables them to better understand their conditions and advocate for themselves.

Karen first heard about QUOD at the British Transplantation Society conference in Belfast, Northern Ireland in early March 2020, which, coincidentally, was when the UKODTRN was launched. QUOD had a stand at the conference and it was here that Karen first met Prof Rutger Ploeg, who told her about the work that QUOD was doing. This initial encounter led to discussions about future collaborations and Karen joining the QUOD Steering Committee. Within QUOD, Karen’s focus is on PPIE and transparency, in terms of QUOD ensuring that they communicate back to the transplant community about the research that is being supported by the biobank. While it can be challenging to communicate complex science in plain language, Karen feels it is crucial that patients are empowered by being able to access and understand the science. The UKODTRN plans to feature QUOD in their newsletter as well as a webinar to keep their audience updated and informed about QUOD’s work supporting research.

Karen feels that QUOD fills a great need by aiming to improve and increase our knowledge and understanding of organs and transplantation, for example, through the identification of biomarkers and the changes that occur from organ retrieval to transplantation and beyond. It is by understanding these changes that we can improve outcomes.

While a typical week for Karen is extremely varied, much of her time is spent speaking to patients about projects that have been presented to the UKODTRN, looking at requests to get involved with PPIE, interacting with researchers, and talking to collaborators and charities, as well as the strategic direction of the network.

In her spare time, Karen swims and will be representing Great Britain in the World Transplant Games in Dresden, Germany in 2025. She describes the Transplant Games as a really good example of how to get transplant recipients back to being a thriving person after years of being unwell, it is also an excellent opportunity to make friends and celebrate life and donors.

The QUOD team is hugely privileged and grateful to have Karen on board, as her lived experience as a transplant recipient and strong desire to make research accessible to all bring a fresh perspective. We look forward to working with Karen on future projects and wish her the best of luck for the World Transplant Games next year.

New QUOD Colleague Questionnaire – Michael Nation

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Michael Nation – Senior Development Advisor

What were you doing most recently before joining QUOD?

I was the Director of the National Unified Renal Translational Research Enterprise (NURTuRE).  In this role and working with a great team I helped to develop the first UK national centralised renal biobank, with cohorts in chronic kidney disease (CKD) and Idiopathic Nephrotic Syndrome (INS). I was also recently involved in the collaborative development of a new cohort in Acute Kidney Disease (AKD). 

What interested you about working with QUOD?

It’s heritage, the great team and its ambitious strategy to accelerate and “de-risk” research and ultimately game change patient outcomes on a UK and international basis. Plus, the challenge as there is a real need in this area.

What does your role involve?

Helping to develop plans that lead to new collaborations, increased funding, new infrastructure and a higher level of sample and data utilisation on a UK and international basis.

Lightning round time:

If you were stuck on an island what three things would you bring?

A piece of flint

A mirror to attract attention from a passing super yacht

Any Bear Grylls’ book

Where’s your favourite place?

Dancing a waltz on a tropical beach with my wife Helen

Finally, what kinds of enquiries should people bring to you, and how best can they reach you?

QUOD: opportunities for future collaboration, profiling and funding – mnation@successfuldevelopment.org

QUOD & Live Life Give Life

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Dr Luke Yates, trustee of the organ donation charity Live Life Give Life, introduces the work of the charity and the exciting new partnership with QUOD

Live Life Give Life is a small UK charity that raises awareness of organ donation and the transformative power of transplantation. We are run by volunteers, who are all affected personally by organ donation and from all perspectives of the transplant journey – as recipients, donors, and survivors of those lost waiting. One of our prime objectives is to encourage people to talk about organ donation with their families. Our work is carried out via awareness campaigns, events and activities, and initiatives such as The Orgamites characters, which have been created to help young children understand organ donation. We also fund small research projects that aim to improve the welfare of (and outcome for) patients who need transplants, and travel fellowships to foster collaborative research for early career researchers.

Live Life Give Life was founded in 2006 by Emily Thackray and Emma Harris both afflicted by cystic fibrosis (CF). The two young women had lost many friends to CF and, at the time, Emily was on the waiting list for a life-saving lung transplant. The shortage of organs and donors inspired Emily and Emma to create a T-shirt campaign to raise awareness and encourage people to sign the organ donor register. Live Life then Give Life was their slogan and their fledgling charity; and went on to attain charity status in 2008. Emily received a transplant is 2007, and a further transplant in 2014, but tragically passed soon after. Emma also received a transplant and continued to fundraise and raise awareness for the cause but very sadly passed away early this year.

In a new project, Live Life Give Life is partnering with QUOD to develop a unique pump-prime funding opportunity to aid transplant researchers utilise this fantastic biobank resource. Watch this space – further details of the grant and how to apply coming soon!

Website: livelifegivelife.org.uk  X: twitter.com/lltgl
Facebook: facebook.com/LLTGL  Instagram: instagram.com/livelifegivelifeuk/

Spotlight on a QUOD Colleague – Prof Colin Wilson

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For this issue of the QUOD newsletter, we caught up with Colin Wilson, Professor of Transplantation and Hepato–Pancreato–Biliary (HPB) Surgery at Newcastle University, NHS-employed Consultant Surgeon, and QUOD Principal Investigator for Newcastle. We spoke to Colin about his academic and clinical roles in transplantation as well as his role within the QUOD programme, including how QUOD is supporting the development of a novel artificial intelligence (AI)-informed assessment of organ quality.

In his role as QUOD Principal Investigator for Newcastle, Colin coordinates specimen collection and onward transport to Oxford. He works with various teams within the Newcastle-upon-Tyne Hospitals Trust; the HPB team delivers the QUOD boxes to Oxford and the organ retrieval team underpins this. Colin actively supports the professional development of his team members and encourages their involvement with QUOD.

Colin leads a team at the NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, which is a collaboration between Newcastle and Cambridge Universities. The programme involves clinical work and registry analyses to look at ways to improve organ utilisation and provide a scientific basis to develop policies in clinical practice around organ utilisation. The programme delivers work packages, protocols, projects, and trials. One such trial is OrQA (Organ Quality Assessment), which, in collaboration with QUOD, is developing a tool that uses AI-driven analysis of photographic images of organs (taken using devices such as smartphones) to predict their suitability for transplantation by assessing factors such as perfusion quality or percentage steatosis (in liver). Colin recalled his experiences as a child using his first camera, the rigmarole of taking the film to be developed, and the wait to receive the prints, whereas nowadays we all have very high-resolution cameras on our phones that could be applied to transform our approach to medicine. His enthusiasm for the use of technology to advance transplantation outcomes is clear and is just one of his visions for the future of transplantation.

Looking ahead, Colin is keen to support medical students aspiring to become transplant surgeons and is actively involved with the North East Surgical Training Academy (NESTAC) training and mentorship programme, which connects students and trainees with mentors. He considers himself to be extremely lucky to be able to support some of the very talented medical students who are interested in careers in transplant surgery. The pathway to becoming a consultant transplant surgeon begins with a one-year laboratory-based MRes project that is written up in a thesis and presented as oral and poster presentations, which may go on to be presented at conferences and meetings, followed by progression to academic foundation doctor (core training level), academic clinical fellow, and finally clinical lecturer. The programme takes around 10 years from start to finish and Colin is very much looking forward to seeing the first person “come off the conveyor belt”, who he first met as a medical student keen to become a consultant transplant surgeon. He has mentored and supported him throughout his career development and says “it is going to be a really big moment that I’m looking forward to”.

Colin’s own journey to become a transplant surgeon began in 1999, when he was working as a Senior House Officer on a gastroenterology ward with Oliver James, Professor of Hepatology, at the Freeman Hospital, Newcastle. It was here that he realised that liver transplantation was key to the successful treatment of many patients with liver ailments. In 2001, he began his PhD, supervised by Prof. David Talbot, on non-heart-beating kidney transplantation, which was novel and challenging work at the time. He then went on to complete his training as a Surgical Registrar from 2006–2012.

While transplant surgery can present challenges, Colin describes his job as rewarding and he is very much future-focused. He is driven by research, developing technology, and building strong teams, and most enjoys creating and delivering novel solutions to overcome (or work around) the hurdles and obstacles facing transplantation. His research aims to identify how to make the best use of the resources available, such as finding ways to overcome non-use of organs from deceased donors and achieve good long-term outcomes for patients, while prioritising safety. He is passionate about supporting the next generation of UK transplant surgeons, who will also face issues for patients with organ failure but may consider newer approaches such as the use of stem cells, AI, or xenotransplantation, which has been approved in the USA but is not currently implemented in the UK.

Colin is unquestionably proud of his hugely dedicated and committed team, comprising particularly talented members, all with broad-ranging areas of expertise and who have won numerous esteemed prizes for their work in transplantation, published cutting-edge research, and are developing “staggering” novel AI work. He mentors his team academically and it is hugely important to him to provide them with an environment in which they can flourish.

Colin describes the QUOD programme as “engaging and outward-looking”, and really values the focus it brings to transplant research. Of particular importance to him are the governance structures in place, in addition to the core biorepository work, as well as the fellowship among like-minded individuals who can build projects on top of the infrastructure that QUOD brings. “It’s not just what QUOD is, but what QUOD has allowed to build around it and the connections that has made it such a valuable resource for UK transplantation.” He believes that the UK is world-leading in many areas of transplantation and QUOD is at the core of that.

In addition to his work in Newcastle, Colin’s job sees him travelling to and presenting at national and international meetings. He will be co-chairing the ESOT Congress 2025 in London, which will focus on sustainability, not just in terms of climate emergency but also workforce and the issues and challenges facing the NHS and European healthcare systems that are struggling to deliver doctors, nurses, and specialists in transplantation.

While his work has taken him to various countries over the years, outside of his busy full-time clinical and academic roles, Colin cherishes time with his family, enjoying activities such as table tennis and travelling together, and is looking forward to a family holiday in the next few weeks.

Interviewed by Jenny Collins.