A Year in Grants - 2018/19

A Year in Grants 2018 - 2019

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Dear All, We are delighted to present an overview of our Grants activity for the twelve months to March 2019. During this period, the Charity has continued its strategy of giving larger and more strategic grants aligned with our vision for transforming patient outcomes in London and beyond, with total grants made of £30m.

We are proud to support the remarkable work of our Partners at Barts Health NHS Trust (Barts Health) and Barts and The London School of Medicine and Dentistry at Queen Mary University of London (SMD). We do this by developing and funding high impact projects with our Partners which focus on transformational medical research, state of-the-art equipment and technology and innovative healthcare projects. Although we focus on London, our projects often have national and international impact.

This booklet highlights all our grants over £50,000 made in the year to end March 2019. We also made grants for less than £50,000 across Barts Health and SMD over the course of the year, of which we are equally proud and which often provide catalytic funding for a variety of projects. These smaller grants are too numerous to include in this booklet, however.

We are extremely grateful to Barts Charity for the substantial investment into strategic awards that will enable further expansion in quality and quantity at SMD. Our partnership with the Charity gives us a unique edge and is fundamental for the delivery of our strategy.

Professor Mauro Perretti – Dean for Research and Research Impact, Barts and The London School of Medicine and Dentistry at Queen Mary University of London

Regards

Barts Charity provide absolutely vital support to our hospitals, our staff and most importantly our patients. Some of our most exciting, state of the art equipment, most innovative research and cutting edge projects are funded by Barts Charity. I am hugely grateful for their role in helping us provide safe and compassionate care to patients in East London and beyond.

Fiona Miller Smith – CEO, Francesca Gliubich – Director of Grants and the Barts Charity Team

Alwen Williams – Chief Executive, Barts Health NHS Trust

The last twelve months have also seen a step change in our voluntary income, harnessing the passion and commitment of supporters and Major Donors and in our hospital fundraising strategy, which will enable us to support Barts Health’s five hospitals further, with more grants being made towards items that are essential to the delivery of the outstanding care we are so proud of. However we want to do much more over the coming years to ensure that we can sustain our current level of giving for an extended period.

Thank you for all your support in the last twelve months, and we look forward to working with you in the coming months and years.

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BARTS CHARITY

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Contents Programme Grants

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Improving neurosurgical operative efficiency with a novel digital robot

Building research facilities for the future

Barts Centre for Adrenal Studies

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Recruiting excellence in cancer research and precision medicine

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Barts Brain Tumour Centre

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epression and psychiatric illnesses in renal D dialysis patients

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L eukaemia/Lymphoma 3D digital diagnostics: A unique novel approach to the future of pathology differential diagnoses J oint protective actions of omega-3 derived lipid mediators

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Barts Charity Rising Star Lectureships

I dentify biomarkers for skin cancer risk prediction and prevention

Large Project Grants

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Establishment of HeartOME1000

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ssessing regenerative potential of A myogenic progenitors derived from CRISPR-corrected human iPSCs for treating muscular dystrophy

Building an antibody engineering platform to advance antibody therapeutic innovation High-dose vitamin D to prevent progression from upper respiratory infections to asthma attacks (the Rescue-D study): A feasibility trial

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Screening for stunting in East London Human tissue-resident immunity to intestinal fungi A YEAR IN GRANTS 2018 – 2019

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Programme Grants

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BARTS CHARITY

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Brain tumour sample A YEAR IN GRANTS 2018 – 2019

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Building research facilities for the future Professor Steve Thornton, Professor Anthony Warrens, Professor Mauro Perretti and Dr Rob Bennett

Barts and The London School of Medicine and Dentistry at Queen Mary University of London (SMD) aims to improve the health and wellbeing of people throughout the UK and beyond through research and teaching excellence.

Awarded ÂŁ6,460,200

Artist impression of the new facilities in the Joseph Rotblat building

by LOM Architecture and Design

Over the past ten years, SMD has experienced unparalleled growth in research power and research output quality.

Researchers in the key strategic areas of cancer, cardiovascular disease, inflammation and preventive medicine have been extremely successful in winning major new grant funding that has huge potential to deliver significant patient benefits through translation of research from bench to bedside and into the wider population.

With these funds the Charity is strategically supporting SMD in a new phase of growth to attract new talents by providing new research laboratories equipped to the latest standard, as well as creating additional and bespoke teaching facilities and office space.

It will ensure the current and ambitiously expanding research programmes are supported, enabling them to reach their full potential to deliver tangible benefits to patients and the community. Providing 6

optimal space to accommodate existing and new staff into SMD will allow them to flourish scientifically and shape the future of research. This will set SMD in the optimal position for the next Research Excellence Framework (REF2021) with augmented quantity without compromising quality.

The expanded portfolio of research and training activities enabled by this project will deliver in terms of translation into patient benefit, high quality publications and further successful grant applications.

BARTS CHARITY

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Barts Centre for Adrenal Studies Professor Morris Brown, Dr Paul Chapple, Professor William Drake, Dr Leo Guasti and Professor Louise Metherell

Disorders of the adrenal glands may develop across the whole age spectrum, from in utero to old age. Broadly speaking, adrenal diseases comprise those that lead to abnormal hormone production (either deficient or excessive) and those that lead to the formation of adrenal tumours, which in turn may be benign or malignant. Some adrenal diseases, such as primary aldosteronism, are considered a major public health issue. Others, such as primary adrenal insufficiency if undiagnosed, and adrenocortical carcinoma if unresectable by surgery, are rare but lethal.

The Department of Endocrinology at Barts Health NHS Trust has grown substantially in recent years, becoming an internationally renowned centre of excellence, linking clinical and academic staff in SMD to facilitate translational research and clinical trials. Clinical cases of great variety and complexity from the entire UK and abroad are investigated and managed within an integrated inpatient ward facility and a designated outpatient investigation unit. Paediatric endocrinology is closely integrated with the adult department’s activities, providing comprehensive care for young patients with endocrine disease.

Awarded £1,467,258

Barts Charity’s investment will support an ambitious programme of translational research and therapeutic innovation, facilitating it into becoming the world’s leading centre for clinical care and translational research in adrenal disease in adults and children. This will impact on treatment and quality of life not only for the 1,000 patients with adrenal disorders attending our clinics annually, but also for patients with adrenal disease worldwide.

Confocal microscope image of two immunolabelled human neuroblastoma cells, Dr Paul Chapple

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Recruiting excellence in cancer research and precision medicine Professor Nick Lemoine, Professor Jack Cuzick, Professor Jude Fitzgibbon, Professor Stephen Duffy, Professor Hemant Kocher, Dr Tatjiana Crnogorac-Jurcevic, Professor Trevor Graham, Professor Louise Jones, Professor Attila Lorincz and Dr Ranjit Manchada Awarded ÂŁ5,167,249

The overall aim of this programme is to recruit internationally recognised senior faculty across various disciplines of cancer research and ultimately increase the critical mass in the area of cancer research at Barts and The London School of Medicine and Dentistry at Queen Mary University of London. This programme focusses on recruiting team leads in the three thematic areas of (1) Cancer prevention and risk reduction, (2) Screening and early diagnosis, and (3) Cancer genomics and evolution, and will provide the necessary infrastructure for these posts over a period of 3 years.

The themes (4) Targeting Tumour Cells and (5) Targeting the Tumour Stroma, that form the second part of this proposal were officially approved by the Charity in December 2017 and March 2018 respectively.

This programme will build upon and accelerate the international reputation of the Barts Cancer Centre (BCC).

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The BCC receives infrastructural funding from Cancer Research UK (CRUK) as one of the Charity’s designated research centres, which supports core research facilities within the building (for example microscopy and animal facilities), as well as providing studentships and other financial support for research. The CRUKBCC funding is based around the five key research themes listed above, that each represent areas of broad research excellence within the institute.

The programme combines skills, abilities, experience and expertise that are specific only to SMD. It will help to build a unique interdisciplinary environment with translational research at its core delivering, wide-ranging and ambitious goals for the benefit of many hundreds of patients within Barts Health NHS Trust and the wider community in the short term and many thousands of patients in the long-term.

BARTS CHARITY

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Cancer genomics and evolution at Barts Cancer Institute A YEAR IN GRANTS 2018 – 2019

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Barts Brain Tumour Centre Professor Silvia Marino and Mr Edward Mckintosh

Awarded ÂŁ1,568,179

Brain tumours kill more people under the age of 40 than any other cancer, and 80% of people diagnosed with a brain tumour die within 5 years. Malignant gliomas are the most common intrinsic brain tumours in adults. They grow highly invasively, cannot be completely resected by surgery and are resistant to conventional anticancer treatments. The overall survival of patients with a newly diagnosed glioblastoma is only 14 months. In fact, survival of these patients has not improved over the last 20 years, a rare exception to the general trend of cancer survival in the UK. This award wishes to build upon the success of the Charity's previous seed funding of ÂŁ200,000 which enabled the Brain Tumour Research Centre to secure additional funding.

When the Centre was established, its main focus was to research the molecular and cellular mechanisms regulating the development and growth of gliomas. The applicants now wish to develop a clinical platform at SMD and Barts Health to ensure basic science discoveries can be swiftly taken to the clinic and more effective experimental treatments can be offered to patients.

Glioblastoma cells growing in a plastic dish, Professor Silvia Marino

This aim will be achieved by building a translational research platform to allow the inclusion of Barts Health patients in research trials, leading to a significant increase in the amount of experimental treatments available to patients.

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Barts Charity Rising Stars Lectureships Professor Mauro Perretti, Professor Steve Thornton and Professor David Kelsell

Awarded £6,137,969

Barts Charity has partnered with Barts and The London School of Medicine and and Dentistry at Queen Mary University of London for a transformational programme to recruit a new generation of lead researchers for the next decade.

The grant will support SMD’s plan to appoint 16 lecturers and support them in their career progression towards independence.

The new lecturers will underpin innovative research in the strategic areas of expertise in cardiovascular medicine, cancer, inflammation, trauma and population health sciences. They will be offered a flexible start-up package including a research assistant and consumables. Their time will be 100% devoted to research.

The programme will build capacity in junior academic positions, ensuring continuity to the quality of academic research conducted at SMD. SMD will support and nurture the new junior academics with the aim to develop well-established researchers and therefore increase the REF2021 headcount submission at the same time maintaining the high quality of research performed and outputs produced.

William Harvey Research Day posters A YEAR IN GRANTS 2018 – 2019

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Large Project Grants

Fluorescence microscopy of muscle microcirculation, Dr Tamara Girbl 12

BARTS CHARITY

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A YEAR IN GRANTS 2018 – 2019

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Establishment of HeartOME1000 Dr Ben O’Brien, Dr James Moon and Dr Gaby Captur

Awarded £278,127

Discovering new effective medicines for treating patients with heart disease is challenging. This is because groundbreaking drug discovery is only possible through the study of hundreds of heart muscle samples from patients, but such samples are difficult to collect.

to address this. They have the expertise, infrastructure, and track-record to safely biopsy hundreds of cardiac patients at the time of their planned heart surgery.

Biopsying the heart in large numbers is not straightforward, however the team at Barts Heart Centre – one of the world’s largest cardiac centres – are best positioned

For the first time, HeartOME1000 will link and analyse clinical, imaging, genetic, small molecule, and heart sample information of 1000 patients with heart conditions. Results will help the applicants discover new forms of treatment, improve diagnosis and delivery of care in cardiology.

Barts Heart Centre staff uniform

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Assessing regenerative potential of myogenic progenitors derived from CRISPR-corrected human iPSCs for treating muscular dystrophy Dr Yung-Yao Lin

Awarded ÂŁ250,401

Muscular dystrophies are debilitating genetic diseases characterised by progressive weakness and wasting of skeletal muscle, which is responsible for voluntary movements and breathing. Gene mutations lead to loss of muscle fibres and their replacement with fat and connective tissue.

in a DMD mouse model. In parallel, they will elucidate molecular mechanisms that enhance skeletal muscle regeneration in the cellular model of DMD.

Current standards of care can delay loss of ambulation, cardiac and respiratory problems, but patients develop progressive weakness leading to immobility. Some muscular dystrophies even cause premature death.

The team aims to advance gene-corrected cell therapy for muscular dystrophies. They will tackle several hurdles using established isogenic pair of Duchenne muscular dystrophy (DMD) patient-specific and gene-corrected pluripotent stem cells, which are capable of generating an unlimited supply of skeletal muscle stem cells.

Furthermore, they will assess whether gene-corrected muscle stem cells contribute robustly to regenerated muscle fibres, replenish the muscle stem cell pool and do not form tumours after engraftment

Generation of human skeletal muscle and muscle stem cells in a dish, Amaia ParedesRedondo and Dr Yung-Yao Lin

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Depression and psychiatric illnesses in renal dialysis patients

Improving neurosurgical operative efficiency with a novel digital robot

Professor Kam Bhui, Professor Magdi Yaqoob, and Dr Livia Arauja de Carvalho

Mr Alex Alamri and Mr Dimitrios Paraskevopoulos

Awarded ÂŁ248,449

Awarded ÂŁ495,000

Depression affects about a quarter of people treated with renal dialysis for end stage kidney disease (ESKD). Untreated depression can lead to premature death and poorer quality of life. Antidepressants and psychological therapies can improve depression. ESKD patients do not usually receive these treatments because physical symptoms and cultural expressions of distress can mask depression, antidepressants may not work well, and patients may be too unwell to agree to take them or cope with their side effects.

Brain surgery is lengthy and requires extended focus and concentration from surgeons. They rely heavily on excellent visual information from operating microscopes to view brain anatomy.

Inflammation is common in ESKD patients and may cause depression. This project reviews the evidence for and tests a new approach to assess and treat depression in ESKD patients. The team will consult patients and carers, and compare markers of inflammation in patients who are not depressed, depressed without inflammation, and depressed with inflammation. They will test if patients with inflammationrelated depression respond better to antidepressants, or anti-inflammatory drugs and anti-depressants.

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Current microscopes are large and cumbersome, and this means the surgeon must stop frequently, re-adjust and re-focus the microscope for a better view, increasing operating time by up to 10%. The surgeon’s assistant also needs to re-adjust whilst the surgeon waits, or the movement will shake the view, which is potentially dangerous. It is also difficult to use instruments during surgery.

Height-mismatches mean that surgeons have to contort themselves into difficult postures, affecting focus and concentration, increasing operating time and putting them at long-term risk of occupational injury.

This funding has supported the purchase of the Modus V digital robot, a state of the art hands-free, robotic operating microscope that can track surgical instruments. This means that surgery is faster, more precise, more ergonomic and will provide gold-standard care for patients and surgeons.

BARTS CHARITY

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Mr Edward McKintosh performing an Awake Craniotomy using the Modus V microscope A YEAR IN GRANTS 2018 – 2019

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Leukaemia and Lymphoma 3D digital diagnostics: A unique novel approach to the future of pathology differential diagnoses

Joint protective actions of omega-3 derived lipid mediators

Dr Timothy Farren and Dr Tom Butler

Dr Lucy Norling

Awarded £267,900

Awarded £231,527

Quantitate analysis of bone marrow is crucial for the diagnosis, stratification and prognosis of leukaemia and lymphoma.

The funding of a Digital Slide Scanner to the Department of Immunophenotyping at The Royal London Hospital makes the department the first in the UK to have access to this type of technology for the digital examination of chromosomes for genetic aberrations.

It is well known that eating a healthy balanced diet is key to maintaining good health, however much less is known about how a bad diet can make diseases including arthritis worse. Recent research has shown that omega-3 fats (abundant in fish oils) can be converted within the body into very effective molecules (e.g. ‘resolvins’) that help switch off inflammation and repair tissue. The underlying hypothesis is that insufficient amounts of these molecules are generated in people that eat a western diet which lacks omega-3 fats.

This innovative technology will allow access to real-time digitised slides of patients’ samples allowing for rapid diagnosis. In addition, it will permit the lab to continue their research programme into the validation of digital pathology for wider use.

This project aims to assess why a western diet worsens arthritis and determine how omega-3 fats switch off the aggressive behaviour of cells within the joint and switch on cartilage and bone repair mechanisms to help restore joint function.

This is important as current treatments for arthritis relieve pain and swelling, yet do not prevent the main cause of disability, which is cartilage damage and joint deformity.

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An arthritic knee joint, Dr Lucy Norling A YEAR IN GRANTS 2018 – 2019

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Identify biomarkers for skin cancer risk prediction and prevention Professor Catherine Harwood and Professor Daniel Pennington

Skin cancers are common human malignancies. Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer with over 50,000 UK cases each year. CSCCs are usually treated by surgery but represent a significant burden for patients and healthcare resources. Most CSCC develop from actinic keratoses (AK), pre-cancers caused by sun exposure.

Less than 1% of AKs progress to CSCC and some regress without treatment.

However, factors determining AK fate are poorly understood and so personalised AK treatment is not yet feasible. As immune-suppressed patients develop CSCC at increased frequency, this project will explore whether immune system status in AK provides a marker and potential driver of progression to CSCC. This would improve our understanding of AK and identify changes that predict skin cancer risk and inform new targets for skin cancer prevention.

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Awarded ÂŁ489,534

Histology of cancer tissue

BARTS CHARITY

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Building an antibody engineering platform to advance antibody therapeutic innovation

High-dose vitamin D to prevent progression from upper respiratory infections to asthma attacks (the Rescue-D study): A feasibility trial

Dr Ahuva Nissim and Dr David Collier

Professor Adrian Martineau, Professor Christopher Griffiths and Professor Aziz Sheikh

Awarded £287,793

Awarded £125,991 The development of innovative therapies for various diseases is an increasingly important research goal for for SMD and Barts Health.

The production of Monoclonal antibodies (mAbs), has become a major asset for the treatment of various diseases including cancer, cardiovascular, inflammation and autoimmune disease. MAbs represent an almost limitless source of therapeutic and diagnostic reagents as they can be synthesised to bind to and treat almost any substance.

This grant is to build specialised antibody ‘libraries’ to support the development of novel antibody-based drugs for use in patients within Barts Health and beyond.

Antibody libraries are constructed using the genomic information found in proteins to allow for fast, high throughput screening of therapies for a specified target. The phage display technique is a widely used method for this type of protein engineering. The use of patient-derived libraries will enrich the repertoire of antibodies produced, allowing for safe and efficient translation into the clinic.

The UK has one of the highest rates of asthma deaths in Europe and Barts Health paediatricians have highlighted asthma as a local public health emergency.

Current approaches to prevention and management of asthma attacks are unsatisfactory. The team previously showed that taking vitamin D supplements not only boosts the immune system to prevent colds and other infections, but also cuts the risk of asthma attacks. As many people forget to take daily vitamin supplements, an alternative approach could be to take a big ‘rescue’ dose of vitamin D at the first sign of a cold to prevent it developing to trigger an asthma attack. With this award, the team will perform a feasibility study before seeking funds for a large definitive trial to test this new approach. This project will increase the understanding of the disease by examining how early intervention with vitamin D modifies the immunological process of acute viral infection and the development of asthma attacks.

A YEAR IN GRANTS 2018 – 2019

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Screening for stunting in East London

Human tissueresident immunity to intestinal fungi

Professor Andrew Prendergast, Professor Leo Dunkel and Dr Helen Storr

Dr Neil McCarthy and Professor James Lindsay

Awarded £499,186

Awarded £131,389

Poor growth in childhood can be due to underlying medical causes or socioeconomic disadvantage. In the UK, children are measured at ages 4 and 10 years through the National Child Measurement Programme (NCMP).

However, pre-school children do not have heights measured systematically, measurements are often not recorded if they are done, and there is no referral system for growth failure.

This project adds research capacity to the applicant’s team and helps establish a new laboratory in the field of anti-fungal immunology at SMD. It will support the development of the new lab and maximise the potential of the Principal Investigator's MRC Career Development Award.

This project is a pilot study that aims to develop a screening tool that would enable early referral and treatment of underlying medical disorders. A multidisciplinary team of academics from across three institutes at SMD has been assembled, including expertise in child health and growth, endocrinology, primary care, school engagement and screening. This project will allow the targeting of pre-school interventions for children whose poor height growth predicts reduced future educational attainment.

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Changes in the balance of gut bacteria have been linked with recent rises in many chronic diseases, but we know very little about how human health is influenced by the fungus that also lives in our intestines.

Children with inflammatory bowel disease (IBD) have increased amounts of intestinal fungus, and patients with inherited problems in anti-fungal immunity suffer from severe gut inflammation. Dr McCarthy recently discovered that human gut tissue can be protected against fungus by a cell type called 'Vδ2' which is common in people but missing in mice. Vδ2 cells are activated by an immune system protein called BTN which detects a bacterial chemical called HMBPP. The proposal will investigate this newly discovered mechanism of anti-fungal immunity in IBD and aims to test whether intestinal Vδ2 cells can prevent fungus growth in the gut in order to protect us against IBD.

BARTS CHARITY

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Mould assay, Dr Neil McCarthy

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Scanning Electron microscopy of a pancreatic cancer cell cultured in a hydro at Barts Cancer Institute

12 Cock Lane London EC1A 9BU 020 7618 1717

bartscharity.org.uk

Barts Charity is a charity registered in England and Wales, no. 212563, and a company registered in England and Wales, no. 7168381, whose registered office is the above address.

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