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Author: Louise Stanley

The BHP Starter Fellowship – Pip’s story

Pip Nicholson is a clinical lecturer in haematology at BHP founder-member the University of Birmingham, and completed his BHP Starter Fellowship between 2015 and 2016. His research is currently focused on translating tyrosine kinase inhibitors to be used as anti-platelet drugs, and investigating the mechanisms of vaccine-induced thrombocytopaenia with thrombosis. He holds research grants from the British Heart Foundation, Wellcome Trust Translational Discovery Fund, the NIHR and a number of pharmaceutical companies, and is also chair of the HaemSTAR Network. He spoke to BHP about how his experience of the fellowship had led him to this point in his research career.

What attracted you to apply for the fellowship?

The fellowship was announced at a really opportune time for me. I’d just had a discussion with my now supervisor about the idea for the research and we’d been puzzling over how we could fund my salary to allow me to be released from my clinical duties. One of the limitations with other fellowships is that they require such detailed background and large amount of preliminary data. This means that doctors without a research background are effectively excluded from getting their foot on the first rung of the research ladder. While competitive, the BHP fellowship (or ITM fellowship as it was known then), didn’t require such extensive background information and the preliminary data required was a reasonable amount that could be generated by someone without any dedicated research time.

What were the benefits of fellowship?

The fellowship didn’t come with any significant strings attached such as teaching requirements. This meant that I could get on with the job of learning techniques and quickly generating further data to submit for larger, prestigious fellowship applications to support a full PhD.

Were there any challenges during the fellowship?

The main challenge was getting a full research fellowship application written and submitted in time for the various deadlines. To a clinician, a year to learn new skills and develop preliminary data seems like a huge chunk of time (my experience is that clinicians in training are happy if they get an hour to work on our own projects!). But the research environment is very different and long periods of time are required to learn skills, iron out issues with laboratory assays, and gain ethical approvals for the work.

While a year is sufficient time to generate data if you are focussed about things, the deadlines for the full research fellowships didn’t fall nicely near the end of the BHP fellowship and meant I had to put in applications before they were really ready. Towards the end of the fellowship I was still left wondering whether I had any ongoing research funding and this led to quite a lot of anxiety. I was fortunate to be placed in a well-funded lab where the brief shortfall in funding between finishing my BHP fellowship and subsequent funding from a British Heart Foundation Clinical Research Training Fellowship could be picked up.

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

I very much wanted to keep my ‘hand in’ clinically, and so I did continue doing some clinical work. I was worried that if I didn’t, I wouldn’t be safe to look after patients when I returned on a more regular basis. So, I undertook in one outpatient clinic a week at the Queen Elizabeth Hospital, and I also did daytime on-calls at weekends at about a 1 in 5 frequency. In hindsight I think this probably slightly hindered my progress in the lab and actually my clinical skills probably wouldn’t have suffered significantly if I’d just stopped doing any clinical work for that year of the BHP fellowship.

Did the fellowship help with your clinical practice?

It definitely helped me identify the area of subspecialist clinical practice I wanted to do long term (i.e. thrombosis and haemostasis). It also gave me time to delve more into the clinical literature of this sub specialist area in order to better understand the pathophysiology and existing treatments and where the current limitations are in our knowledge.  I also gained experience in dealing with ethics applications and working with NHS Trust Research and Development departments which have been a useful skill.

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

Without a doubt, if it wasn’t for the BHP fellowship I can’t see how I would have got my foot in the door of the clinical academic world. I’m now a clinical lecturer, chair a national research network and am in the process of applying for intermediate clinical research fellowships to support me in a consultant role and as a senior clinical lecturer. I wouldn’t be in this position without that initial year of funding that the BHP fellowship provided.

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

Talk to people who have successfully been award the fellowship and have completed it and moved on to higher research degrees and other fellowships. Ask them to look at their successful applications to use as a template. Talk to them about their experience of the fellowship itself. Identify a supportive research environment and speak to various members of that research group (e.g. PhD students and post-doctoral researchers). They are the ones who will be able to tell you what the research training in that group is really like. Don’t just rely on your impression of the supervisor!

BHP launches Seed Fund to invest in innovation

Today (20 June) Birmingham Health Partners officially launches its BHP Seed Fund – a new initiative which will kick-start innovation by providing researchers with up to £100,000 initial investment.

Designed to support our culture of research-embedded healthcare practice while simultaneously addressing common challenges across our member organisations, the Seed Fund will bring together healthcare professionals, academics, students and entrepreneurs, to deliver the initial steps towards implementable solutions. The aim of the fund is to provide early-stage support and proof-of-concept for projects which will have swift impact on patients outcomes and experiences, but can also be further developed or rolled out more widely.

Working with NHS partners, BHP has identified a number of broad themes which are both of key importance to the region, and are also primed for innovation and investment. We will therefore strongly support applications for projects which directly relate to these priority areas for our region:

      • Health data and AI
      • Engineering into health settings
      • Sustainability
      • Health inequalities
      • Health systems and evaluation

BHP Chair, Ed Smith, commented: “Birmingham Health Partners is delighted to offer this opportunity for innovation, funded with seed money to stimulate support and growth for health-based solutions for the West Midlands and beyond. We hope and expect this funding will be exciting for applicants and deliver meaningful contributions.”

Colleagues from all healthcare professional backgrounds working across all BHP’s partner organisations are welcome to apply.

Visit our BHP Seed Fund page for full details

‘Cellular brake’ offers clue to autoimmune response during immunotherapy

A ‘cellular brake’ which could prevent lung cancer patients from developing a dangerous autoimmune response during treatment has been identified by scientists.

The finding, published in Nature Communications, is the first clue to the cause of autoimmune toxicity, in which patients develop dangerous additional conditions during immunotherapy treatment.

Immunotherapy works by enabling the body’s immune cells (T cells) to engage with and kill tumour cells. They do this by suppressing proteins called immune checkpoints. These exist to prevent an immune response from being so strong that it destroys healthy cells in the body.

Autoimmune toxicity, which includes conditions such as pneumonitis, or inflammation of the lungs, can affect lung cancer patients undergoing immunotherapy treatment. Pneumonitis is responsible for around 35 per cent of treatment-related deaths in lung cancer patients.

Given the increasing use of immunotherapy treatment against cancer, the management of these reactions has become a significant healthcare challenge. Most commonly, clinicians will recommend discontinuing the treatment and exploring other options.

Led by Professor Gary Middleton, the team, in the University’s Institute of Immunology and Immunotherapy pinpointed a specific biological response among patients who develop autoimmune toxicity. They found a ‘cellular brake’ – a protein which would normally limit the activity of the T cells – is missing or not functioning properly.

By identifying patients who lack this cellular brake, it may be possible to recognise patients at high risk of developing severe autoimmune complications.

Lead author Dr Akshay Patel said: “Immunotherapy is an extremely important weapon in cancer treatment and so identifying people who are at particular risk of developing these potentially life-threatening autoimmune conditions is key to weighing the risks and benefits of different treatments. It would enable clinicians to closely monitor high-risk patients, develop preventative strategies, or pursue alternative treatments altogether.”

The research was funded by Cancer Research UK and the National Institute for Health and Care Research (NIHR) Biomedical Research Centre.

The BHP Starter Fellowship – Shaun’s story

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

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 CouncilCancer Research UK, and the Wellcome Trust.

New research collaboration will develop precision cell therapies for blood disorders

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.”