New QUOD Colleague Questionnaire: Emma Greig – Transplant Research Project Manager

In September, QUOD welcomed our new Transplant Research Project Manager – Emma Greig. Emma has agreed to share a bit more about herself and her role at QUOD.

What were you doing most recently before joining QUOD?
I was living in Toronto working as a Project Manager at an advertising agency.

What interested you about working with QUOD?
I started working in advertising shortly after graduating from university. After working in advertising for a few years I wanted to eventually transition to a role that was more impactful. When I was planning my move to the UK I found the QUOD job posting and it seemed like the perfect fit!

What does your role in QUOD involve?
The main focus of my role is to make sure projects finish on time, in scope, and within budget. I spent the first few months of my role organizing the QUOD finances, but now I am focusing on setting up commercial projects and helping organize the logistics of the ADMIRE project that will be using QUOD samples.

Lightning round time:

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

Water, shelter, a survival kit. I may have watched a season or two of Survivor during the lockdown and am thinking about what they usually need!

Where’s your favourite place?
Toronto

What was your primary COVID-19 lockdown survival method?
I started crocheting during the lockdown and just made my first blanket.

Finally, what kinds of enquiries should people bring to you, and how best can they reach you?
Anything related to project management or crocheting. I can be reached at emma.greig@nds.ox.ac.uk.

Spotlight on a QUOD Colleague – Lewis Simmonds, Data Analyst QUOD

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This week I ‘met up’ with QUOD colleague Lewis Simmonds, of NHS Blood & Transplant.  Lewis is a statistician and provides QUOD with the data required for researchers.

Lewis joined the QUOD family in July last year after graduating from Bristol University with a First-Class degree in Maths and was given the task of streamlining the way QUOD’s data is gathered and extracted.

When a research scientist requests clinical data (for example donor, retrieval and recipient follow up data) to go alongside samples from QUOD, they must first select the data variables appropriate to their research question, which are listed on the QUOD website. This process then generates a spreadsheet that is communicated to our QUOD Data Coordinator here in Oxford, who then completes the data access request and sends it over to Lewis so that he can extract the requested data from the NHSBT database. 

When Lewis first joined us in the summer this process was rather lengthy and variables were colour coded into categories according to the lead times to receive the data, these were anything from under a month to more than three months.  This system has worked well until now, but as QUOD has become more well known, its activity has increased and the requests for samples have multiplied.  Lewis has turned this around by building a new database that produces the information easily at the click of a button, that will eventually be able to be run by any member of trained NHSBT staff within a much shorter timescale. It has taken quite some work to harmonise the data into a uniformly functioning format with fine tuning of the interactions between bodies of data but he says this work is almost complete. In just 6 months Lewis has transformed the process and QUOD is ready for action!  He will continue to work with QUOD to make changes to the website and before long researchers will be able to reap the benefit.

I asked him if he had learned his skills during his university studies.  He told me that he had learned Python, R, SQL and SAS, all of which are high level programming languages, at university but it is his fascination with how programmes interact with data structures and tables that led him to play around with programming in his spare time, testing his theories in developing games amongst other things.  His latest interest has expanded to website design and how the information that a website user taps into an interface is routed behind the scenes to create datasets, purchases, bookings or information collection.  He told me he has always been interested by how different systems can work together and loves exploring the possibilities to render systems compatible to a desired purpose. 

Lewis is based in Bristol and like a lot of us is still working from home though he enjoys going into the office one day a week.  The thing he likes best about his role is the creative freedom he has to seek out ways to improve systems and increase efficiency.  When he first took on the role, the biggest challenge was to familiarise himself with the many databases and their different properties in terms of function, formatting and location.

The most unusual thing Lewis has done in a job was when he was still at school.  As a fresh-faced sixth former he helped a friend run a mail/internet order business selling glowsticks, glow ears, flashing dog collars, baseball caps and light up bouncy balls!

In his spare time, other than tinkering with programming he is very keen on music with a particular penchant for Drum & Bass which has led him to DJing in and around Bristol on the weekends.  In lockdown he developed a taste for Hip Hop and Rap and he also enjoys cycling and a round of golf!

QUOD named UK Biobank of the Year 2022!

The UKCRC Tissue Directory and Coordination Centre awarded QUOD first place in the UK Biobank of the Year.

The UK Biobanking Showcase is the UK’s leading event for those who work in biobanking and human tissue research and took place online over three days with interesting talks and presentations from biobanks all over the UK.

Please see below some extracts from the Judging Panel’s comments: 

‘… the Biobank provides a highly specialist resource which is of immense value to the organ donation field.  Despite being so specialised, … QUOD nevertheless responded flexibly during the pandemic to participate in the RECOVERY trial and in the development of the NHSBT Oxford COVID BioArchive (COBA).  …  The panel particularly commended the quality and range of the Biobank’s outreach and engagement activities which unusually included providing work experience to college students during the pandemic.’

Professor Ploeg, Director of QUOD (Quality in Organ Donation) and Dr Sarah Cross National Operational Coordinator of QUOD are delighted with this wonderful achievement: ‘This award is an important milestone in our pursuit to increase research in donation and transplantation, increasing organ utilisation and providing more and better organs for our patients’. They congratulate the whole QUOD team including the Specialist Nurses in Organ Donation and NORS teams based in the 61 NHS partner trusts across the UK, as well as the core team in Oxford, the Directors of NHS Blood and Transplant, the Medical Research Council and our academic collaborators without whom none of this would have been possible.

Dr Maria Kaisar – Developing new ways to assess kidneys so transplants last for longer.

With funding from Kidney Research UK, a team of researchers from the University of Oxford, the University of Nottingham and University College London will develop ways to assess donor kidneys and predict how well they will work after transplant.

Having a kidney transplant is the best treatment for kidney failure, but the demand for donated kidneys is high.

To save more lives, doctors are now accepting kidneys from older or higher risk donors. These kidneys may also work less well after transplantation. This can have devastating effects, causing patients once recovering from transplantation to also go back on to dialysis, and wait for another transplant.

Right now, doctors cannot accurately assess donor kidneys. This makes it difficult to predict how well a transplant will work and how long a kidney will last after it has been transplanted.

Thanks to Kidney Research UK’s grant award of £237,626, (in partnership with the Stoneygate Trust), the ADMIRE study ‘Assessing Donor kidneys and Monitoring Transplant Recipients’ aims to address this clinical challenge.

Dr Maria Kaisar

Dr Maria Kaisar from Oxford University’s Nuffield Department of Surgical Sciences (NDS) is the Principal Investigator on the study and leads a team of co-investigators from NDS (Professor Rutger Ploeg, Dr Edward Sharples, Mr Simon KnightMr James Hunter and Dr Sadr Shaheed), the Oxford Big Data Institute (Dr Alberto Santos Delgado and Dr Philip Charles) and the Radcliffe Department of Medicine (Dr Elizabeth Tunnicliffe)

Dr Maria Kaisar and her team will utilise the Oxford Transplant Biobank (OTB) and the Quality in Organ Donation (QUOD) biobank to look for marker proteins in the donors’ blood samples. They use these samples to develop a mathematical model to predict how well donor kidneys will work after transplantation. The successful model would allow doctors to accurately assess kidneys and only transplant those that will function well. It could also identify suitable kidneys previously deemed too high risk to transplant.

With Professors Sue Francis and David Long from the University of Nottingham and University College London, the NDS team will use the QUOD X platform to also develop a monitoring strategy. MRI scanning methods will be performed on both the donor organ before it is transplanted, and later on after transplantation. This will allow us to monitor how well the transplanted organ is functioning.

“I am absolutely delighted that our study received this funding award by Kidney Research UK in partnership with The Stoneygate Trust,” said Maria. “This funding will enable us to bring scientific and clinical expertise together in collaboration, to develop novel non-invasive methods to better assess donor kidneys and, predict how well a transplant will work in the recipient. We also envisage that our planned scientific work will offer many opportunities to our early career scientists, to further develop their skills and research expertise in studying kidney disease. “

Letizia Lo Faro – Use of QUOD samples in research ‘Case Study’

My name is Letizia Lo Faro and I am a Post-Doctoral research scientist in the Oxford Transplant research group. I have so far used QUOD samples in 4 or 5 separate research studies. In one of these, conducted together with Ms Flavia Neri (University of Padova), we were interested in studying the molecular features of donor kidneys with acute kidney injury (AKI) having different functional outcomes after transplant.

Letizia Lo Faro

Once we fully characterised our research question, we moved onto donor sample selection. We decided to compare 4 different groups of donors: with or without AKI and each with good (≥45 mL/min) or poor (<45 mL/min) function (eGFR) 12 months post-transplant, for a total of 40 donors. We maximised the difference between outcomes as much as possible and to allow for fair comparisons we decided to match the groups for several other variables (donor age and gender, BMI, cold ischaemia time, recipient age, recipient gender…just to name a few). I believe appropriate sample selection is a key step in such retrospective studies and we engaged with the QUOD Data Manager earlier on in the process. This provided us with a great overview of all the variables available and also made sure our groups were nicely balanced.

Once we were happy with the donor selection, we proceeded with requesting the samples from the biobank. In this case they were full RNAlater frozen kidney biopsies and formalin-fixed paraffin-embedded (FFPE) kidney tissue slides. In this study we were interested in studying protein expression, so first of all we processed the tissue biopsies to mechanically homogenise them and extract the proteins. Later on the proteins were quantified and the expression of 17 proteins of interest was analysed by Western Blotting (a technique where a mixture of proteins is separated on a gel, based on the molecular weight, and, following transfer on a membrane, proteins of interest are identified by binding to specific antibodies). Results were then analysed with statistical tools.

A set of FFPE slides was then utilised for histological assessment, by standard staining with haematoxylin and eosin (H&E), to quantify chronic and acute tissue damage. One additional set of slides was utilised for confirmation of the western blotting results by immunohistochemistry, another method which allows to check for the presence of certain proteins/products in a tissue, by binding with labelled antibodies.

Results from this study were presented at the British Transplantation Society meeting last year and we are currently finalising a manuscript for publication.

Our results suggested that specific molecular patterns are recognizable in acutely inured kidneys that proceed towards worse function after transplantation. In particular, Peroxisome proliferator-activated receptor gamma (PPAR gamma) specifically increased after acute injury that progressed to worse function, underlining a potential role of metabolic dysfunction in the development of kidney disease (Figure 1).

Figure 1. The protein PPARg, quantified by western blotting analysis, is significantly increased in AKI kidneys with poor outcomes 12months post-transplant.

Our findings have helped identify potential molecular mechanisms involved in the progression of acute kidney injury to chronic kidney disease and post-transplant dysfunction and may constitute a therapeutic target of further interventions aimed at improving the quality of donated kidneys with an acute injury.

Working with QUOD samples has allowed us to really dive deep into the study of molecular mechanisms of kidney injury and the availability of different sample types also allowed us to apply various techniques and methods to validate our findings.

New QUOD Colleague Questionnaire: Philippa Wren – QUOD & Transplant Research Groups Administrative Assistant

In June, QUOD welcomed our new QUOD & Transplant Research Groups Administrative Assistant – Philippa Wren. Philippa has kindly agreed to share a bit more about herself and her role at QUOD:

Philippa Wren

What were you doing most recently before joining QUOD?
Surviving lockdown and home schooling my beautiful daughters, Grace 9, and Evelyn 2. My previous role involved PA, Administrative and Secretarial support for a Regional Manager. I also have a background in Marketing and Events organising.

What interested you about working with QUOD?
I have missed working within a team and hoped to work within a reputable academic organisation. I have always been fascinated with surgery and liked the thought of working somewhere that makes a difference. The two together seemed like the perfect opportunity for me..

What does your role in QUOD involve?
I provide administrative support for the QUOD and Transplant Research teams. I maintain the contact@quod inbox, social media platforms and website as well as take minutes for various meetings. I also place orders, liaise with suppliers of lab consumables and support Prof Ploeg’s EA in looking after his diary, organising his meetings and travel arrangements.

Lightning round time. Tea or coffee?
Tea – I love it!

Favourite place in Oxford?
There are so many. I would have to say the view of Oxford Skyline from the top of South Parks.

Best holiday trip ever?
Venice. There’s no other place quite like it.

Primary COVID-19 lockdown survival method?
Lots of long walks… and wine!

Finally, what kinds of inquiries should people bring to you, and how best can they reach you?
All inquiries are welcome. If I can’t answer it I can redirect you to someone who can. You can contact me via email contact@quod.org.uk or philippa.wren@nds.ox.ac.uk

Spotlight on a QUOD Colleague – Maggie Stevens

by Susan Patchett

For this edition of the QUOD Newsletter I was delighted to be able to catch up with Maggie Stevens, ODT Specialist Nurse for Research at NHS Blood and Transplant.  Maggie is responsible for the operational and service delivery for the great number of research studies that NHS Blood and Transplant operate and support alongside QUOD.

Hers is a varied role and involves setting up Specialist Nurse training, carrying out risk assessments for new studies, and helping teams draw up action plans and standard operating procedures (SOPS) ensuring that they comply with their ethics approval, regulatory requirements, and are fit for purpose for Specialist Nurses in Organ Donation (SNODs) to follow safely and effectively.

When I asked Maggie if she could describe a typical day she told me that there was no such thing.  One day she can be going through a risk assessment with the ODT Research Team and Quality Assurance for a large clinical trial and identifying potential operational, regulatory and safety risks.  Other days she will be auditing consent records to be sure all has been carried out to the letter.  She meets regularly with research leads in all the regions, ensuring they are up to date with studies that are being set up and also cascading training that they will undertake with their teams. 

Problem solving is a large part of her role and can range from SNODs raising issues if they aren’t comfortable with a particular process, to a shortage of boxes. 

Maggie works very closely with QUOD and helps us iron out issues that may arise in terms of sample collection, logistics, and other operational problems.  She forms the crucial link between QUOD and the SNODs.  After QUOD’s activity was paused during the first wave of COVID-19, she helped us with the mammoth task of restarting operations, updating SNOD training and finding ways around getting QUOD boxes delivered when so many personnel were working remotely between on-call shifts.

The elements of her job that she likes the most are the people and the research and innovation – ‘There is always wonderful new research going on such as the SIGNET trial and I find contributing to this work is really satisfying.’  She also said that her job is made very special by her colleagues, Hannah Tolley (OTDT Research Project Manager) and Emma Lawson (OTDT Innovation and Research Lead)). They work closely as a team linking in with other stakeholders to ensure that ODT research is facilitated safely and effectively. They also sit together alongside QUOD’s National Management Team.

I asked her if nursing was the career she had envisaged.  She laughed and said when she decided on nursing she was actually working at an agricultural college in Chelmsford, driving tractors and fruit picking.

Like all of us through the pandemic, Maggie has had to decamp her office to her home but she said she was one of many NHSBT staff who couldn’t bear sitting still when there were those working themselves to the bone on the front line so, she got herself deployed back to her original A&E department for six weeks.  She loved being back with her former colleagues.  I asked if she felt worried during that stint and she said ‘you just do what you have to do.’

Maggie Stevens is not all about work and loves an adventure in the great outdoors.  She has climbed Ben Nevis with colleagues for organ donation week and spent a couple of months travelling alone around Alaska where she saw whales and bears and met some wild and wonderful people that she will never forget.  She is also a fan of rock music and has tickets to see the Foo Fighters very soon!

COVID BioArchive Update

Since March 2020 the QUOD team has been supporting the national effort in the fight against COVID-19. QUOD’s extensive biobanking expertise, infrastructure and personnel have served to set up the NHSBT Oxford COVID BioArchive (COBA).  Over 68,000 blood samples from convalescent plasma donors who have recovered from COVID-19 have been collected and processed as part of the NHSBT Convalescent Plasma programme. In addition, since September COBA has received over 18,000 samples collected from recipients of convalescent plasma and monoclonal antibody treatment in the international RECOVERY trial.

These samples were used by a number of research groups, NHSBT and Public Health England in a variety of projects, including assessment of novel COVID-19 tests, characterisation of COVID-19 antibody function, and analysis of the efficacy of convalescent plasma treatment. With this COVID BioArchive, we have been able to establish a robust and sustainable resource for future validation and research helping us to gain better insight into COVID-19 and anticipate targeted intervention.

You may have heard that on 15th January randomisations of patients into convalescent plasma was paused following disappointing interim results that showed no evidence that convalescent plasma has an overall benefit on patient outcomes in moderately ill people.  Work to search for evidence of benefit in subgroups before organ damage and hospitalisation occurs is now under consideration.

Given the quantity of samples now available, it has been decided that collection of further plasma samples will not be resumed.  The news may seem discouraging, however an important scientific question has been answered.  In terms of the scale and volume of the operation this was a considerable undertaking that has proved that the QUOD infrastructure in close collaboration with the NHSBT’s Blood Service has the capacity and versatility to help and meet such an important demand.

Over 250,000 samples are currently stored in the COVID BioArchive to be used for dedicated research questions and validation of novel tests. Applications are welcome from national and international research groups or health care authorities.

BTS & NHSBT Congress 2021 Roundup

by Rebecca Vaughan

This year, as has become our new norm, the BTS Congress 2021 was hosted using an online platform, allowing delegates to experience interactive plenary sessions and parallel sessions similar to when attending the conference.  However unique to the online experience was the opportunity to access content ‘on-demand’, including the additional option to listen to pre-recorded abstract talks, at a time that suits you.  Although, many were saddened by the lost opportunity to meet with colleagues and friends, the commitment from BTS to provide an opportunity for clinicians and researchers to gather and share their research from the last 12-months was an absolute success and credit to the organisers. 

For this conference, I submitted an abstract titled ‘Brain death specific glomerular matrix degradation profiles are associated with long-term graft dysfunction in kidney transplant’ on behalf of our teams at NHSBT and the Oxford Transplant research lab in University of Oxford.  This abstract was selected for presentation as part of the ‘Medawar Award Session’, where my abstract and presentation was considered for the award along with three other researchers who also submitted abstracts for basic science in transplantation. I feel incredibly fortunate to have had our abstract considered for the Medawar award, and was excited to highlight how we have utilised invaluable samples from the QUOD biobank.  Our research utilised 60 kidney biopsies from the QUOD biobank from both DBD and DCD donors.  Our work described a DBD specific degradation profile for cytoskeletal proteins in donor kidneys that linked to suboptimal 12month posttransplant function.  Our research was considered novel in that it indicates that protein degradation may affect donor kidneys and post-transplant function. Preparing for my live presentation was also a memorable experience, involving many rehearsals with my supervisors Dr Kaisar and Prof Ploeg and colleagues, many adjustments and changes before the final live talk.

Our group also had a second opportunity to present our research work involving the analysis of  QUOD samples. A second abstract titled ‘Protein profiles in deceased donor kidneys associated with 12-Month post-transplant kidney function’ was accepted as a pre-recorded talk, presented by our colleague Priyanka Joshi.  This study utilised 185 kidney biopsies from the QUOD biobank for proteomic analysis, comparing DBD and DCD donors with differing functional outcomes 12mth posttransplantation.  This study showed that protein markers in donor kidneys associate to posttransplant outcomes and indicate which biological pathways may play a role in determining the donor kidney quality.

Our research work has highlighted the value of the QUOD samples; based on the collection protocols, these samples provide us with confidence regarding sample quality and collection continuity.  Importantly, our sample selection and analysis is linked with the clinical and demographic metadata that we receive from the National Transplant Registry from NHSBT. The combination of the selection of QUOD samples and donor and recipient metadata makes a unique research resource.  

The overarching focus of the BTS congress was the impact of COVID-19 on transplantation, with NHSBT statistics team highlighting changes in trends of donation and transplantation due to the pandemic.  An invited keynote speaker focused on ‘resilience’  encouraging people to reflect on their own resilience and how they have adjusted to the inevitable changes that have come along with a global pandemic, whilst looking to the future with reasonable caution but also excitement.  Several talks also touched on emerging perfusion technologies and the improvements they may have on outcomes in the future, and evaluating single centre experiences.

Overall the BTS Congress 2021 was a great success despite the mammoth task of moving the conference to an online platform.  The opportunity to bring together scientists and clinicians to discuss research, trends and experiences in transplantation is essential to moving the field forward.  The conference provided an excellent opportunity to showcase research work, however the opportunity to interact with each other; ask questions, discuss and debate ideas was lacking and greatly missed.  The representation of QUOD, NHSBT and the University of Oxford was strong, and hopefully more researchers were inspired to consider QUOD samples for their ongoing work.

Congratulations to Charlotte Brown (Wales Kidney Research Unit) and Maria Ibrahim (NHSBT Bristol) who were awarded the 2021 Medawar Medals at the congress. Click here to read about their research.

Increasing the Number of Organs Available for Research (INOAR)

Until recently, only organs removed for transplant, but subsequently not transplanted were available to researchers.  Thanks to a collaboration between QUOD and Newcastle University, in partnership with NHS Blood and Transplant, new arrangements have been implemented that will allow hearts, lungs and pancreases which are unsuitable for transplantation to be retrieved for research purposes. This will greatly facilitate ongoing research into developing ways more donated organs can be converted into successful life-saving transplants.

Clare Denison, Lead Specialist – Innovation and Research ODT at NHS Blood and Transplant, said: “This is a significant moment for our organisation and researchers across the country. INOAR will change the face of transplantation and ultimately improve patient outcomes and quality of life in the future.”

This development is particularly exciting for diabetes researchers. Almost 4 million people in the UK are living with diabetes. The condition occurs when the pancreas doesn’t produce enough insulin, or when it can’t produce any at all, which leads to blood glucose levels being too high. Until now, the pancreas has not been removed, or even sampled following the death of people with diabetes during organ donation for transplantation.  Research into the mechanisms preventing normal pancreatic insulin production in diabetes has therefore been limited to the small number of post-mortem samples currently stored in the UK.

Dr Elizabeth Robertson, Director of Research at Diabetes UK, said: “This is an exciting step forward that we hope will rapidly advance our understanding of the causes and progression of diabetes … world-class scientists will now have vital access to pancreatic tissue, propelling our knowledge of diabetes forward and bringing us a step closer to a world where diabetes can do no harm.”