Author: Louise Stanley

The BHP Starter Fellowship – Shaun’s story

Written by Louise Stanley on 08/06/2022. Posted in Birmingham Health Partners.

Shaun Thein is a Clinical Research Fellow in Respiratory Medicine at the University of Birmingham, and undertook his BHP Starter Fellowship between November 2020 and November 2021. He’s currently in the second year of an internally-funded PhD, investigating neutrophil dysfunction in COVID-19 patients, as well as undertaking a PGDip in Medical Education. He took some time out to share his experience of participating in a research fellowship during the pandemic.

What attracted you to apply for the fellowship?

I applied for the BHP Starter Fellowship as I had developed a project during my academic clinical fellowship (ACF), but due to the time restrictions and COVID-19 redeployment, I hadn’t accumulated enough pilot data for a strong fellowship application. The BHP fellowship allowed me to collect more data to present a stronger case.

What were the benefits of fellowship?

The main benefits of the fellowship have been the long stretch of dedicated academic time and funding. This has allowed me to recruit patients in a block and have more time to become involved with other projects. I was able to defer finishing the modules I completed as part of my ACF, giving me the option to submit for an MRes if I was unsuccessful in my clinical research training fellowship application.

In addition, I was able to access the support of the College of Medical and Dental Sciences, attending a Scriptoria workshop, statistics courses and weekly seminars.

Were there any challenges during the fellowship?

Due to a further COVID-19 restriction, patient recruitment to the clinical trial my project was linked to was suspended. As a result, I shifted focus to use my skillset in another project, investigating COVID neutrophil dysfunction.

Unfortunately, I was unable to secure funding after interview, so it was challenging to find a way for me to continue my research and PhD. I was fortunate that my supervisor was able to internally fund another year of research for me to complete experiments and patient recruitment.

How much clinical work did you do while undertaking your fellowship?

I did extra out-of-hours shifts at a local NHS Trust to supplement my salary, as there was a significant drop when not doing on-call shifts. I continued this throughout my fellowship as it also helped me to feel more confident in maintaining clinical competencies – especially procedural skills.

Did the fellowship help with your clinical practice?

There was significant patient recruitment as part of my project, involving screening, reviewing imaging and consenting patients for research. I have also been involved in helping with clinical trial research as part of my group. Together this has helped me gain confidence in this aspect of clinical work, and I will be more proactive in recruiting patients and advertising clinical trials in the future. However, being away from day-to-day ward and clinical work will always generate a degree of anxiety when returning.

Do you feel that the fellowship has helped you with your career development and aspirations?

Yes! It has given me the opportunity to complete a PhD, which I would have not been able to do otherwise, and has enabled me to be involved with clinical research trials and work with leaders in these fields. Being released from an on-call rota has also allowed me to pursue other personal developmental opportunities. For instance, I completed a PGCert in Medical Education and I am continuing with the PGDip this year. I have also been appointed as the Chair of the British Thoracic Society Specialist Trainees Advisory Group.

What would your advice be to anyone thinking of applying for a BHP fellowship?

There is no reason not to!

However, it is important to apply with a project plan, supervisor and supportive group, and to think about alternative plans and contingency plans if funding applications are not successful.

While a year seems much longer than the 3 month blocks in the ACF, it goes by very quickly – the more that you can hit the ground running, the more you will be able to get out of the year.

Identifying DNA repair genes holds promise for improving cancer treatment

Written by Louise Stanley on 01/06/2022. Posted in Cancer outcomes, Experimental medicine.

A new way in which cancer cells can repair DNA damage has been discovered by researchers at BHP founder-member the University of Birmingham.

These new findings shed new light on how cancer cells react to chemotherapy and radiotherapy, and also uncover a new way in which cancer can become resistant to particular treatments. These insights may enable clinicians to select different cancer treatments that can be more targeted to specific patients.

Repairing damage to DNA is vital for cells to remain healthy, and to prevent diseases like cancer from developing. Understanding how DNA repair works is crucial to better understand how cancer develops, and also how anti-cancer treatments like radiotherapy and chemotherapy can be used effectively to induce DNA damage that kill cancer cells.

In the study, published in Molecular Cell, a team of researchers in the University’s Institute of Cancer and Genomic Sciences pinpointed two proteins that had not previously been identified in the DNA repair process.

Professor Martin Higgs, Associate Professor for Genomics and Rare Disease in the Institute of Cancer and Genomic Sciences, explained: “This research has the potential to change how cancer patients are identified for treatment and also how they become resistant to different drugs, which will improve treatment efficiency as well as patient outcomes.”

Called SETD1A and BOD1L, these proteins modify other proteins called histones which are bound to DNA. Removing these two proteins changes how DNA is repaired, and makes cancer cells more sensitive to radiotherapy. Loss of SETD1A and BOD1L also makes cancer cells resistant to certain anti-cancer drugs called PARP inhibitors.

Lead author Associate Professor Martin Higgs explained: “This is the first time that these genes have been directly linked to DNA repair in cancer. This research has the potential to change how cancer patients are identified for treatment and also how they become resistant to different drugs, which will improve treatment efficiency as well as patient outcomes.”

The team hopes the work could eventually also lead to new inhibitors being developed that would allow clinicians to re-sensitise cancers that have become resistant to certain therapies.

The research was funded by the Medical Research Council, Cancer Research UK, and the Wellcome Trust.

New research collaboration will develop precision cell therapies for blood disorders

Written by Louise Stanley on 19/05/2022. Posted in Cancer outcomes, Experimental medicine, Health inequalities.

The Universities of Birmingham and Oxford are to take part in one of five NHS Blood and Transplant (NHSBT) research units launched today.

The £20m programme, co-funded by the National Institute for Health and Care Research (NIHR) and NHSBT – is aimed at providing new technologies, techniques or insights that will benefit donation, transfusion, and transplantation. The NIHR BTRUs are partnerships between universities and NHSBT.

Many of the work strands in the new units could result in new technologies and practices that can then be delivered at scale by NHSBT, helping to save and improve even more lives. Much of the work will be aimed at reducing health disparities and improving access to new treatments.

Researchers at the Universities of Birmingham (UoB) and Oxford are part of the NIHR BTRU in Precision Cellular Therapeutics – also working in collaboration with University Hospitals Birmingham (UHB) NHS Foundation Trust. UoB and UHB are both founding members of BHP, with a long history of collaborative research and development.

The aim is to develop new kinds of cell therapies for blood disorders and blood cancer, and improved systems for following up patients receiving treatment to better support their care.

There is a wide range of work in the package but examples include:

- Transplants work in blood cancer patients because some of the donor immune cells attack and eliminate the cancer, but these cells can also attack the donors own cells and cause a complication called graft versus host disease (GvHD). The team will seek to identify and clone the receptors that enable the T cells to target the cancer cells while reducing the toxicity due to GvHD seen in patients. The ultimate aim of this research is develop a novel clinical trial, with NHSBT, via its cell therapy manufacturing infrastructure, expanding these cancer specific T cell receptors for use in patients.
- There is a shortage of suitable cell donors for minority communities. Cord blood units from babies may be a match but not have enough cells to be successful in adults. The team will seek to expand and gene edit the stem cells in cord blood, so they could be used with increased safely in a wider range of adults. NHSBT will support the translation of this research through to early phase clinical trials, providing process development, manufacturing and quality control expertise. This initiative will drive wider access to cord blood transplant.
- It is important that patients from all communities benefit from cell therapies. The team will seek to better understand how patients access the newer cell therapies and how they perceive the benefits of treatment. The team will develop new digital technologies that improve care by enhancing interactions between the patients and their doctors and nurses.

The BRTUs are funded by £16m from the NIHR and £4m from NHSBT, with research goals set to meet NHSBT’s requirements, to be delivered between 2022 and 2027.

The products could be manufactured at the latest NHSBT sites including major new centres such as the new cellular therapies laboratories in Barnsley and the forthcoming Clinical Biotechnology Centre in Bristol.

Dr Gail Miflin, Chief Medical Officer for NHSBT, said: “By collaborating with academia, these five new Blood and Transplant Research Units will help us to deliver on our mission to ‘save and improve even more lives’ and drive innovation to inform future clinical practice and improve patient outcomes.

“For example, the supply-demand gap for solid organs continues to grow. We will explore the use of organ perfusion technologies to maintain and enhance the quality of organs, improve organ preservation and increase organ utilisation. This will enable more patients to receive the transplant they need.

“And by building and analysing new data sets to track and demonstrate the impact of our interventions will lead to better understanding and improved outcomes. We already do this well for solid organs, but do not currently understand the outcomes for people who receive blood or stem cells. We will work with partners to build integrated data sets for these patients, focusing on the multi-transfused, especially those with sickle cell disease where a clear health inequity exists.

“To maximise the value and impact from our research, we will accelerate the translation of innovation into practice. The NIHR BTRUs will be an important vehicle for this in the longer term.”

BHP welcomes new Professor of Regenerative Medicine

Written by Louise Stanley on 16/05/2022. Posted in Experimental medicine.

Professor Ivan Wall has been appointed as Professor of Regenerative Medicine with the Institute of Immunology and Immunotherapy at BHP founder-member the University of Birmingham.

Professor Wall joins us from Aston University and has a well-established relationship with the University of Birmingham as the Lead for the Centre for Advanced Therapies Manufacturing Training. His research group works on stem cells and extracellular vesicles, with emphasis on industrial translation and scale up production – his ambition is to see Birmingham become a hub manufacturing cell and gene therapies that local patients can benefit from.

To mark Professor Wall’s latest appointment with the University, the Institute of Immunology and Immunotherapy sat down with him to learn more about his background and expertise:

What research and industry work do you currently undertake?

My academic research spans stem cells, tissue engineering and bioprocessing. I am particularly interested in the role of mesenchymal stem cells in regenerative medicine, both via direct differentiation towards regenerative cell types but also via their secretion of paracrine signalling vehicles such as exosomes. Exosomes enable cells to communicate with each other and current research points to stem cell-secreted exosomes as important cues for regeneration of injured tissues. My research team has created novel cell lines, demonstrated scalable production and examined cell stimulation methods to enhance potency. Outside of academia I have co-founded two companies: FourPlus Immersive, which creates virtual reality training simulations for GMP cell and gene therapy manufacturing; and Quest Meat. Both companies are based in Birmingham.

What made you become interested in regenerative medicine?

I undertook a PhD in wound healing and my early research focussed on understanding why some wounds in aged or diabetic patients do not heal very well. This spurred an interest in how stem cells are the building blocks for tissue and organ formation, with the aim of understanding how stem cells might be used to drive regeneration of aged or injured tissues. In 2009 I became a lecturer at UCL, working in regenerative medicine bioprocessing, which enabled me to bring together my interest in working with stem cells to treat disease with industrialisation strategies to scale up production for clinical applications.

What is Quest Meat and how did you come about co-founding this organisation?

Quest Meat is a startup that is creating cultivated meat. I co-founded this company with Dr Petra Hanga (now UCL) and former board members of a UK regenerative medicine company and we are based here in Birmingham. We have been able to take our knowledge of scaling up stem cells for medicine and apply it to future meat production. We are doing this because global food production in its current form is not sustainable and, with a growing global population and climate change creating pressure on existing food systems, we need a radical new approach to food production. As a parent I want my children to eat nutritious food that has not been intensively farmed, used antibiotics that may cause health problems, or will accelerate environmental damage. As a scientist and CEO of Quest, I can work with a brilliant team to create a healthy and sustainable alternative.

What are the opportunities and challenges facing future cell and gene therapies?

Cell and gene therapies are transforming healthcare and we are now seeing some truly remarkable treatments emerging that are curing patients of rare and life-threatening diseases, including rare forms of cancer that have not responded to conventional treatments.

Even though these medicines are still in their early days, the rate of development of new treatments means they are becoming more and more prevalent in hospitals and so over time more patients will benefit from them. The main challenge is in being able to manufacture them consistently and affordably, especially as some manufacturing batches only treat a single patient. A second critical challenge is in training enough people to grow the workforce needed for this rapidly growing industry – there is a huge skills shortage. University of Birmingham is at the forefront of addressing these challenges, with the National Training Centre for Advanced Therapies Manufacturing and also excellent advanced therapy manufacturing cleanroom capabilities.

What key advice would you give to researchers considering scaling their research into industry?

Think about what manufacturing for your final product would look like early in the translation cycle. A lot of effort is required to manufacture medicines that will be administered to patients. For example, regulatory guidelines around good manufacturing practice (GMP) must be adhered to, to show that those manufacturing processes consistently deliver the required product quality. Everything from the cleanroom environment, manufacturing equipment, processes and personnel must be monitored and documented. Any changes to manufacturing later on will require re-validation which can cause significant delays to the product development cycle.

Healthy Mum, Healthy Baby, Healthy Future: Report Sets out Vision to Deliver Safe, Effective and Accessible Medicines for use in Pregnancy

Written by Louise Stanley on 11/05/2022. Posted in Birmingham Health Partners, Maternal health.

In a UK-first report launched today, in the House of Commons, leading figures from charity, healthcare, industry, law and academia have outlined a collaborative vision for UK leadership to improve maternal health. The Healthy Mum, Healthy Baby, Healthy Future: The Case for UK Leadership in the Development of Safe, Effective and Accessible Medicines for Use in Pregnancy report proposes a clear roadmap to improve the lives of millions of people, not just for women while they are pregnant, but for future generations.

Download the report Healthy Mum, Healthy Baby, Healthy Future: The Case for UK Leadership in the Development of Safe Medicines for Use in Pregnancy [PDF, 2mb]

Globally, over 800 women and 12,000 newborns die every day from preventable pregnancy-related complications – that is one woman and 17 babies every 2 minutes. Pregnancy complications affect two lives in one short period of time, yet only two medicines have ever been developed specifically for pregnancy-related conditions, and not a single new medicine for some of the most serious pregnancy-specific conditions has reached women in decades.

Over the past year, a Birmingham Health Partners led Policy Commission – co-chaired by Baroness Manningham-Buller, Co-president of Chatham House and Professor Peter Brocklehurst, University of Birmingham – has heard from key stakeholders on how best to develop safe, effective and accessible medicines for use in pregnancy. Compelling evidence gathered throughout the process has informed eight critical recommendations which, if implemented by government, will successfully prevent needless deaths and find new therapeutics to treat life-threatening conditions affecting mothers and their babies.

Key proposals include strengthening the UK’s research capabilities to address gaps in our biological knowledge; more effective clinical trials support; and harnessing collaborative partnerships between government, universities and the pharmaceutical industry. Importantly, the report advocates for women who have been historically excluded from clinical trials to be a vital part of future research, ensuring they are not left behind and can benefit from modern medical advances. The UK, with its existing track record of pregnancy research, and lifelong NHS health records, is uniquely placed to lead this overdue and vital reform, working alongside global partners to deliver real change.

Commenting on the report, Co-chair, Baroness Manningham-Buller LG, DCB, FMedSci said: “When I was asked to become joint chair of the Commission that has produced this report, I am ashamed to say that I wasn’t aware that there was an acute problem. Despite being at Wellcome for twelve years and Imperial College for six, I had no idea that research into conception and pregnancy was largely neglected and that virtually no drugs had been developed and trialled for pregnant women in the many decades since thalidomide. This leaves women at the mercy both of general diseases, the diseases of pregnancy and drugs which are usually unlicensed. The evidence taken by the Commission in its inquiry convinces us that this urgently needs to change. We suggest how.”

Co-chair, Professor Peter Brocklehurst said: “This report represents a clear and timely platform to improve the care we provide to pregnant and breastfeeding women, by increasing the availability of safe, effective and accessible medicines for their use. The Commission’s role was to provide a blueprint for action and will provide ongoing support in implementing the recommendations set out in this report, as there is an urgent need for action to address this underserved area of medical need. Without it, women and babies will continue to die when they could be saved. They will continue to experience long-term health effects, disability and distress, which might be avoided.

“We strongly urge the scientific, clinical, industry, regulatory, governmental and public sectors to come together to address the recommendations of this Commission. The UK has the opportunity to transform maternal health across the world, improving the lives of mothers, their babies and future generations – let’s not waste it.”

Yasmin Golding, campaigner from the Epilepsy Society, who continues to be affected by the lack of safe and effective medicines said: “As a mixed race woman with epilepsy there are pregnancy risks I cannot avoid, but many I should be able to in the age of modern medicine. This report gives me and other women hope that in the future they will be able to spend more time enjoying pregnancy and less worrying about avoidable risks that threaten them and their baby.”

Sandra Igwe, founder of The Motherhood Group and Co-chair of the National Inquiry into Racial Injustice in Maternity Care welcomed the report by saying: “Giving a voice back to those who are ultimately the most affected is crucial, and an imperative step for us mothers advocating for ourselves. All women, regardless of race, age, and socioeconomic background should be allowed to have safe and effective medicine during their pregnancy. It’s key in building trust, offers more choice, and lowers potential health risks – a springboard in the right direction. These recommendations will specifically further help women like me, who due to the colour of our skin, face health inequalities within maternity care.”

Find out more about Birmingham’s holistic and collaborative approach to maternal health research on our new research spotlight page

Improving access to quality post-injury care can save lives

Written by Louise Stanley on 11/05/2022. Posted in Health inequalities.

A major study led by BHP founder-member the University of Birmingham will help reduce unnecessary deaths in developing countries from injuries caused by accidents or violence.

Every year five million people die due to injuries like road traffic accidents, burns, falls, or violence – with 90% of these deaths in Low- or Middle-income Countries (LMICs).

Backed by £2.9 million of NIHR funding, University of Birmingham (UK) and University of Stellenbosch (South Africa) researchers will build on partnerships with experts in Ghana, South Africa, Rwanda, and Pakistan to explore how to overcome barriers to accessing quality care after injury and reduce the likelihood of death or disability.

Experts will use a ‘four delays framework’, which looks at where delays occur in people seeking, reaching, receiving, and remaining in good quality care after injuries, to collect information on delays and their effects on patient outcomes. They will develop visualisations for policy makers to see where to intervene to reduce delays suffered after injury and produce maximum health benefits.

The project builds on a recent study funded by the NIHR led by University of Birmingham and experts in Rwanda which identified 121 barriers to access to quality injury care in three countries across sub-Saharan Africa: Ghana, South Africa and Rwanda.

Researchers discovered that whilst there were a large number of barriers in total, only 31 (25.6%) of these were shared across all three countries, suggesting that solutions to improve access to quality care after injuries may be highly contextually dependent.

Also, only just over half of these common factors (18/31, 58%) were related to delays in receiving quality care at the healthcare facility, suggesting that investment needs to be made in overcoming delays in seeking or reaching care.

Justine Davies, Professor of Global Health Research at the University of Birmingham, explained: “Injuries in LMICs are common and their number is expected to increase, but death and disability after injury can be substantially reduced if people reach healthcare facilities in a timely manner. Understanding access to quality injury care is critical to improving patient outcomes. By partnering with organisations in Ghana, South Africa, Rwanda, and Pakistan, we will develop solutions for future study in these, and similar countries. Our research has already identified many barriers to quality care in Rwanda, Ghana and South Africa. However, as few of these are shared across countries, solutions to reduce the risk of post-injury death and disability will need to reflect circumstances in each country.”

The diversity of cultures, economies, and injuries in partner countries will allow researchers to identify delays and solutions that can be applied across different settings and others that are transferable outside of the four countries of this study.

Study leaders will also train four PhD students and 14 junior researchers in countries with low resources. Training will be done through the development of research hubs in partner countries – these hubs will continue and train future LMIC researchers beyond the project’s end.

Researchers will also work closely with patients, community members and leaders, healthcare providers, and policy makers to understand how to translate the findings of the study into real world solutions.