NIHRDataInsights/HRCSData huggingface dataset:
Title: The University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge
Funder: Wellcome Trust

Abstract: Since 2013, the University of Cambridge Metabolic Research Laboratories (MRL) has developed into a world-leading centre for basic and applied research in obesity and related metabolic disease. Underpinning funding from Wellcome, which has provided new clinical research facilities and other crucial core support, has been central to this success. Importantly, this endeavour has been undertaken in partnership with the MRC, who have funded a new Unit, the Metabolic Diseases Unit (MDU), which is embedded in the MRL. The MRL, together with the MRC Epidemiology Unit (Dir. Wareham) and cognate clinical facilities, form the Wellcome Trust-MRC Institute of Metabolic Science (IMS) which operates seamlessly from basic science through to population science, translational research and delivery of ambulatory care within a single co-ordinated institute. The current bid is focused on further developing world-class metabolic research within the MRL through core support for clinical and animal model research as well as underpinning laboratory science at an internationally leading level. Given the centrality of bioinformatics to all contemporary biomedical research, we have placed a particular emphasis on development of this area for the next phase of our evolution.


Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS;METABOLIC AND ENDOCRINE;STROKE;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL
Title: Dietary management of type 2 diabetes in primary care
Funder: Wellcome Trust

Abstract: It is possible to reverse type 2 diabetes - where people return to normal blood glucose control without medications - through significant weight loss, using total diet replacement programmes (“soups and shakes” diets). However, diets using real food may be more acceptable to some people, and potentially more sustainable. My recent study demonstrated that it was possible for nurses to support patients with obesity and type 2 diabetes to adopt a real-food low-carbohydrate diet, helping them lose weight and improve their blood glucose in the short term. However, it is not clear what effects these diets have on appetite (which influences whether they might work longer-term), and whether other patient groups may benefit. I will run an experimental study to investigate the effects of low-carbohydrate weight-loss diets on appetite in people with type 2 diabetes. I will also run a pilot study to test if people with type 2 diabetes without obesity can adopt this low-carbohydrate diet, and whether this improves their blood glucose control. These studies will inform the design of a full-scale trial testing whether low-carbohydrate weight-loss diets are effective for people with type 2 diabetes longer-term, and whether they should be recommended as part of routine care.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: CANCER AND NEOPLASMS;METABOLIC AND ENDOCRINE;STROKE;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL
Title: Healthy, sustainable and equitable: Integrating knowledge on food choice to optimise interventions
Funder: Wellcome Trust

Abstract: Changing diets could lead to substantial benefits both in terms of health and environmental impact, with the urgent need to change food consumption being increasingly recognised. Drawing on evidence from interventions targeting unhealthy diets could accelerate progress towards more sustainable diets by quickly narrowing down the choice of interventions to improve food selections. However, we need to ascertain whether key differences between healthier vs. more sustainable foods (including social norms, preferences and knowledge) impact on intervention effectiveness, and/or contribute to inequalities in responsiveness to these interventions.This programme of work will examine differences in the impact of interventions targeting (a) healthier vs. less healthy foods and (b) more vs. less sustainable foods, and whether impact differs by socioeconomic position (SEP). It will identify key moderators and mediators of the impact of interventions, and the extent to which these contribute to any differential impact by intervention target or SEP.The programme comprises (1) a conceptual review; (2) experimental studies; (3) field studies in worksite cafeterias and in stores; (4) secondary analyses of purchasing data (e.g. from supermarkets). Identifying the moderators and mediators of dietary interventions will help prioritise the most promising interventions for sustainable and equitable diets.

Lay abstract: We urgently need to make food consumption more sustainable. Evidence from interventions targeting unhealthy diets could help quickly narrow down our choice of interventions to increase sustainable food selections. However, we need to ensure that the effectiveness of interventions does not change when targeting sustainability. We also want to identify interventions that work for those in all socioeconomic positions, so these do not increase inequalities. To test this, I will: (1) review the existing literature; (2) conduct a series of experiments; (3) test predictions from the review and experiments by running interventions in cafeterias and stores; (4) examine existing purchasing data (e.g. from supermarkets). My work aims to identify factors that influence how people respond to dietary interventions, providing key insights into how far we can draw on evidence from interventions on healthier diets. This will help identify the most promising interventions to create sustainable and equitable diets.

Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: CANCER AND NEOPLASMS;METABOLIC AND ENDOCRINE;STROKE;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL
Title: Dissecting the role of aryl hydrocarbon receptor in thermogenic adipose tissue
Funder: Wellcome Trust

Abstract: The obesity crisis has reached epidemic proportions and represents one of the most significant global public health challenges. The recent discovery of energy dissipating brown adipose tissue (BAT) in adult humans has raised the possibility of targeting BAT for the treatment of obesity. Indeed, studies in humans and mice have demonstrated an inverse relationship of BAT activity with obesity and metabolic syndrome. I propose to explore the potential of natural dietary compounds that are sensed by the aryl hydrocarbon receptor (AHR) as novel inducers of BAT activity. I will identify the physiological role of AHR in thermogenesis and utilize conditional gene-targeting approaches to define cell-autonomous functions of AHR in specific cell-types within BAT. Importantly, I will determine whether dietary AHR ligands, such as phytochemicals and microbiota metabolites, can induce the thermogenic activity of BAT, promote energy expenditure and improve metabolic disease in the context of obesity. To elucidate the mechanisms by which AHR modulates thermogenic programs, I will identify its direct transcriptional targets in specific cell-types using ChIP-seq and RNA-seq. Together, these studies will provide important insights into the regulation of thermogenesis by specific dietary factors and may facilitate the use of natural AHR ligands for the treatment of obesity.

Lay abstract: Two functionally distinct classes of adipocytes exist in both mice and humans. White adipocytes store energy while brown adipocytes burn energy to generate heat through a process termed thermogenesis. The principal function of brown adipose tissue (BAT) is to protect against hypothermia, but BAT is also considered an attractive therapeutic target for the treatment of obesity through its ability to promote energy expenditure. However, therapeutic agents that promote BAT activity safely are currently lacking. My data suggest a role for the aryl hydrocarbon receptor (AHR), a transcription factor that recognises dietary compounds, in the regulation of thermogenesis. I aim to identify the cellular and molecular targets of AHR in BAT by combining conditional gene-targeting, RNA-seq and ChIP-seq approaches. Importantly, I will determine whether dietary AHR ligands can enhance thermogenesis and improve metabolic disease. These studies may facilitate the use of dietary AHR ligands for the treatment of obesity.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS;METABOLIC AND ENDOCRINE;STROKE;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL
Title: Cellular Force Microscope.
Funder: Biotechnology and Biological Sciences Research Council

Abstract: AFM is a standard tool for measuring the mechanical properties of cells and tissue with sub-cellular resolution. It is widely used to obtain the elastic modulus of cells and to look for variations across different cell types, between different disease states, or due to external perturbation. Our understanding of cell mechanics is increasingly reliant on the capabilities of AFM. However, there is a fundamental issue with measurements as they are currently made, particularly when applied to softer cell types and tissue. Current AFMs are simply not sensitive enough to force or accurate enough in their measurements to perform many of the experiments they are used for, resulting in errors of up to 100s of percent. These are systematic errors for most ways of analysing data, so they do not result in broad distributions, and experiments are repeatable when the same measurement conditions are used, but the actual numbers obtained for modulus are incorrect. The solution is to use much more sensitive cantilevers, meaning both softer and smaller. Such small soft cantilevers are commercially available for a different application, and will be adapted for use in probing cell mechanics. We will address the issue that cantilever deflection is not accurately measured by incorporating a traceable interferometric detection system, providing several advantages for making mechanical measurements of this type. The resulting Cellular Force Microscope will enable accurate measurement of Young's Modulus with errors less than 5% even for the low moduli found in soft animal cells and tissue. We will combine instrument development with application to two challenging systems: measuring the mechanical properties of the very soft cells found in the peripheral nervous system (PNS) namely Schwann cells and neurons, and measuring how the elastic modulus varies across the interior of a bone, a model tissue and important in understanding what controls the site of breast cancer metastasis in bone.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING)
Health categories: CANCER AND NEOPLASMS;NEUROLOGICAL
Title: Understanding the needs of homecare workers supporting people with dementia and cancer
Funder: Chief Scientist Office, Scotland

Abstract: People with dementia, supported by family carers, prefer to live at home, often relying on homecare services as part of their support structure. Many do not think homecare workers understand their specific needs (Alzheimer’s Society 2016). Dementia and comorbid conditions will intensify challenges for homecare workers and the number of people with dementia and cancer is increasing. We want to know (i) what information and education works best for the homecare workforce (ii) what people with dementia and cancer and their family carers expect from homecare worker support and (iii) what they think the difficulties are.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: CANCER AND NEOPLASMS;NEUROLOGICAL
Title: Marie Curie Palliative Care Research Department
Funder: Marie Curie

Abstract: Background Our vision and our mission statements directly mirror those of the Marie Curie charity which supports the majority of our work. Vision A better life for people and their families living with a terminal illness. Mission To help people and their families living with a terminal illness make the most of the time they have together by delivering and disseminating world class research. Summary Our strategic plan sets out how we plan to improve the quality, quantity and impact of the research that we undertake. Over the next five years, we will: • Maximise the dissemination and impact of our research • Value our existing staff and train the next generation of palliative care researchers • Focus our research onto our core areas of strength: i) Palliative care in seldom-heard groups – seldom-heard groups includes those groups of patients who have not traditionally found it easy to access palliative care services and includes those with dementia, children and young people, non-malignant diseases (particularly liver disease) and the homeless or vulnerably housed. ii) End of life care - This involves a particular focus on the management of the last few weeks and days of life. Particular issues around this phase of a terminal illness include the need for accurate prognostication, the importance of clear and empathetic communication and the optimum management of symptoms (agitation, pain, fatigue). • Obtain more external peer review funding


Research activity codes: 7.2 END OF LIFE CARE;7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT)
Health categories: CANCER AND NEOPLASMS;NEUROLOGICAL
Title: The role of dendritic cells in immune checkpoint inhibition in brain metastases
Funder: Medical Research Council

Abstract: Despite the great promise of anti-PD-1 and anti-CTLA-4 therapies in melanoma, ~44% of melanoma patients fail to respond and the efficacy in triple negative breast cancer (TNBC) remains limited. Thus, a better understanding of the underlying mechanisms is required to enable the improvement of therapy. This should include improvement of the efficacy in the brain, as brain metastases (BrM) develop in up to 60% of metastatic melanoma and ~35% of TNBC patients, and are associated with very poor prognosis. Recent clinical trials provided evidence for the efficacy of anti-PD-1, anti-CTLA-4, and their combination in melanoma BrM. Importantly, due to the distinct immune-specialized characteristics of the tumour microenvironment in the brain, such as lack of lymphatic vessels in the brain parenchyma, immunosuppressive characteristics of tumour draining lymph nodes (TDLNs) and the blood-brain barrier, the molecular mechanisms need to be addressed in the specific context of BrM. My study will focus on dendritic cells (DCs) as the major antigen-presenting cell type, and thereby complement the studies on T cells, NK cells, microglia and macrophages in the context of immune checkpoint blockade in BrM that are currently ongoing in the lab. I will use recently established tumour transplantation and hematogenous models of melanoma and TNBC BrM, in which clinically observed intracranial efficacy of anti-PD-1/anti-CTLA-4 combination can be faithfully recapitulated. I will determine which DC population is critical for the intracranial efficacy of immune checkpoint blockade, how DC migration to the TDLNs differs between intra- and extracranial tumour site, and whether DCs at the two locations differ in their molecular profiles. Key findings will be validated on human BrM tissue obtained from patients that underwent immunotherapy as compared to immunotherapy-naïve patients. This is expected to reveal potential strategies for the enhancement of anti-PD-1/anti-CTLA-4 efficacy.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS;NEUROLOGICAL
Title: SenseCheQ: Community-based sensory testing for early identification of Chemotherapy Induced Peripheral Neuropathy.
Funder: Medical Research Council

Abstract: Chemotherapy induced peripheral neuropathy (CIPN) affects 30% of patients receiving chemotherapy to treat cancer. CIPN presents with numbness and pain in a glove and stocking distribution. There is no effective preventative or therapeutic treatment, and the only mitigation is chemotherapy dose reduction/switching, which is a difficult clinical decision. Detection of CIPN relies on patient report and clinical examination which lacks sensitivity in early CIPN. Quantitative Sensory Testing (QST) is the 'gold standard' assessment of sensory function but it is not in routine clinical use for pragmatic reasons. To enable early detection of CIPN we propose to develop an easy-to-use sensory testing device "SenseCheQ" to allow patients to monitor their nerve health at home. This will provide early, accurate assessment of sensory function to detect nerve damage and potentially avoid chronic neuropathic pain. This will be achieved with iterative and modular device development cycles through collaboration with bio-electronic engineers and patient partners. SenseCheQ will safely deliver automated QST protocols (warmth detection, cool detection and vibration detection), with simplified data capture and be able to transmit that information remotely. This project will synergise with the APDP PAINSTORM consortium, who will prospectively recruit a cohort of patients due to undergo chemotherapy. This cohort will undergo formal QST during their treatment as well as clinical monitoring. A subgroup of these patients (n=20) will have home QST with the SenseCheQ, within a feasibility study, with measures obtained before treatment starts and at intervals during their chemotherapy. This parallel collection of QST data will enable direct comparison of the device with clinical sensory phenotyping. The project maps the path for delivery of a novel device capable of giving patients and clinicians better and earlier information to optimise and personalise their cancer treatment.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS;NEUROLOGICAL
Title: Use of 'Axon-like' Nanofibers to quantify Glioblastoma cells migration
Funder: Wellcome Trust

Abstract: Background: Out of all brain tumours types in adults, Glioblastoma Multiforme (GBM) is the most common and aggressive. Migrating GBM cells infiltrate brain tissue by spreading along nerves and render therapeutical intervention and surgery problematic. novel approaches are desperately needed to target these cells and that’s our focus. Approach: My project aims to mirror the internal conditions that a cancer cell ‘experiences’ in the human brain with artificial nerve-like substrates. We will first measure the capacity of GBM cells to migrate on human nerve fibres. Then we will investigate the relevant biological signals needed for GBM cells migration. Finally, we will mirror these signals with proteins and coat plastic material in the form of fibres acting as ‘fake-nerve’ tracks for cell migration. Impact: This artificial material will enable us to study how GBM cells differ from healthy cells and from patients to patients. This will be used for future screens to identify novel therapeutics by slowing down the migration of the GBM cells. Moreover, combined with existing catheters in clinical use, the fibres will form the basis for novel medical devices. They could act as a ‘decoy nerve trap’ to extract the infiltrating cancer cells for diagnostics and for therapies.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS;NEUROLOGICAL
Title: Towards a randomised primary chemoprevention trial of curcumin in children and young adults with familial adenomatous polyposis
Funder: Children with Cancer UK

Abstract: FAP is an autosomal dominant condition caused by a germ-line mutation in the Adenomatous Polyposis Coli (APC) gene. Affected individuals are predisposed to developing cancer, most commonly of the gastrointestinal tract. Colonic adenomas typically develop during the mid-teenage years and almost all patients will develop colorectal cancer (CRC) if they are not identified and managed at an early stage. The safest preventive strategy is currently surgical resection of the colon when polyposis develops usually when patients are between 15 and 25 years of age. Up to half of patients may experience complications following this surgery. Chemoprevention is the administration of natural or synthetic compounds to delay or prevent carcinogenesis. There are extensive pre- and early clinical data demonstrating that curcumin (an extract of the spice turmeric) is a safe and effective chemotherapeutic agent at reducing the polyp burden in models of FAP. We ultimately propose to design and conduct a clinical study to assess whether curcumin treatment delays the need for surgery and/or prevents cancer in young patients with this disease. Research into clinical trial protocols has demonstrated that where trials require informed consent, assessing patients' perceptions at the initial stage leads to better outcomes. We therefore aim to conduct a questionnaire study of patients and parents of children affected by FAP. In addition national FAP specialists and potential collaborators shall be surveyed. The data obtained shall be used to inform the design of the proposed clinical study.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: CANCER AND NEOPLASMS;ORAL AND GASTROINTESTINAL
Title: Does cognitive behaviour therapy enhance swallowing outcomes in head and neck cancer? A feasibility study
Funder: Department of Health (England)

Abstract: Head and neck cancer survivors endure major swallowing problems following treatment, impacting on health and well-being. This study aims to develop a cognitive behavioural(CBT) model, addressing the way people manage and think about dysphagia, to be delivered in combination with traditional swallowing therapy. The intervention will be piloted on a small cohort of patients. Expected outcomes include a CBT model of dysphagia, a swallowing intervention package and a study design for a definitive trial. The projected benefits are an earlier return to oral feeding, improved compliance with therapy, improved swallowing-specific quality of life and problem-solving approach to dealing with symptoms


Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: CANCER AND NEOPLASMS;ORAL AND GASTROINTESTINAL
Title: Development and preliminary testing of a tailored pre-treatment swallowing intervention package for patients with head and neck cancer.
Funder: Department of Health (England)

Abstract: Head and neck cancers and its treatment result in severe difficulties in eating, drinking and swallowing. A pre-treatment intervention programme may help patients engage in rehabilitation and form basic habits which could enhance swallowing function and recovery after treatment. This study aims to develop and test a tailored swallowing intervention package which includes a swallowing assessment, targeted exercises and specific behaviour change techniques. The feasibility of the intervention will be examined in this small scale study. The results will inform a subsequent larger study to assess effectiveness. An effective intervention will optimise swallowing recovery and quality of life after treatment.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: CANCER AND NEOPLASMS;ORAL AND GASTROINTESTINAL