Elucidating the stem cell basis for skin field cancerisation
Grantee: Dr Girish Patel, Senior Lecturer at the European Cancer Stem Cell Research Institute, Cardiff University, Wales
Amount: DKK 1,704,758
Grant category: Research Grants in open competition
Year: 2017
Geography: United Kingdom
Gish Patel from Cardiff University in Wales leads an international collaboration of experts in a project that investigates the signalling pathways responsible for malignant transformation of skin epithelial cells. The hope is to identify novel therapeutic targets for future drug discovery and development.
Epithelia are continually exposed to environmental carcinogens and therefore, cancers of epithelial tissues called carcinoma, account for 85% of all cancers and 78% of all cancer-associated mortality.
Many carcinomas arise from pre-malignant transformation as intraepithelial neoplasia, also referred to as field cancerisation (FC). FC can give rise to multiple primary cancers and is a feature of malignancies involving many organs, including the skin.
The team hypothesises that the mechanism in skin FC arises from dysregulation of a particular signalling pathway. This is based on results from a murine model on Epidermodysplasia Verruciformis, where the team uncovered a novel keratinocyte stem cell (KSC) basis for the FC.
This is potentially relevant to FC in other tissues and the team targets utilisation of an innovative multiple-strategy approach to determine a drug-targetable signalling pathway involved in malignant transformation and expansion of this novel KSC population.
The LEO Foundation Award 2016 – Gold Award
Grantee: Dr. Amaya Virós
Amount: DKK 1,000,000
Grant category: LEO Foundation Awards
Year: 2016
Geography: United Kingdom
Presented to Dr. Virós who has made important contributions to the area of skin research by describing mechanisms behind the development of squamous cell carcinoma and melanoma. She has published in top-ranking scientific journals and received a number of prestigious awards, including a recent Wellcome Trust Intermediate Clinician Scientist Fellowship to set up her laboratory at the Cancer Research UK Manchester Institute in the newly-built Manchester Cancer Research Centre, UK, which is based at The University of Manchester.
Dr. Virós will focus her future research on the under-researched area of skin cancer and ageing. Ageing skin appears to have unique properties and patterns of tumour development that may explain the surprising increase in aggressive primary melanoma and mortality from this disease. Her aim is to identify the factors in elderly people that make them more prone to developing melanoma and less likely to survive once they develop the disease.
A longitudinal investigation of skin barrier development from birth and the validation of early predictors of AD risk: the skin testing for atopic dermatitis risk (STAR) trial
Grantee: Dr Simon G. Danby, Independent Research Fellow, University of Sheffield Medical School, Professor Michael J. Cork and Mr J. Chittock, University of Sheffield, and Dame, Professor Tina Lavender and Dr Alison Cooke, The University of Manchester
Amount: DKK 2,115,500
Grant category: Research Grants in open competition
Year: 2016
Geography: United Kingdom
Atopic dermatitis (AD) is one of the most common chronic inflammatory skin conditions and prevalence of the disease seems to grow. Early onset of AD is often followed by development of other allergic conditions such as food allergies, asthma and allergic rhinitis – all together the most chronic diseases of childhood and a major financial burden to health services.
Evidence suggests that a skin barrier defect is the primary event in development of AD.
With this research project, a longitudinal neonate/infant cohort study, the team led by Dr Simon G. Danby seeks to investigate the development of the skin barrier from birth, before the development of AD, to 12 months of age, when the majority of AD cases have developed. The team has extensive experience in the characterisation of the skin barrier in AD patients and in conducting clinical trials in neonates.
In the study, the team will compare three technologies for the quantification of established biomarkers attributed to skin barrier function and AD severity, for their accuracy and feasibility at predicting onset of AD by 12 months of age.
In addition, the team’s multi-analytical approach may provide new insights into skin barrier development in neonates and the identification of tools that could help determine who do and do not go onto develop AD. The study thus has the potential to help drive forth a new generation of patient solutions specifically designed for neonates at risk of developing AD.
International Project on the Global Epidemiology of Psoriasis: Development of the Global Psoriasis Atlas
Grantee: Darren Ashcroft, Professor of Pharmacoepidemiology, The University of Manchester, UK, Chris Griffiths, Professor of Dermatology, Head of Dermatology Research Centre, University of Manchester, UK, & Matthias Augustin, MD, Professor and Director, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg, Germany
Amount: DKK 6,370,000
Grant category: Research Grants in open competition
Year: 2016
Geography: Germany, United Kingdom
The LEO Foundation supports the project “International Project on the Global Epidemiology of Psoriasis: Development of the Global Psoriasis Atlas”.
The atlas (GPA) will be a seminal work with focus on epidemiological research that will allow researchers and medical practitioners to compare incidence and prevalence of psoriasis between populations in different countries and thus yield a global ‘picture’ of the disease burden of psoriasis
The work with the GPA is done in a project group with three of the world’s leading international dermatology organisations: International League of Dermatological Societies (ILDS), a global organisation representing 148 dermatological societies worldwide; International Psoriasis Council (IPC), a not-for-profit organisation comprising leading international psoriasis experts dedicated to advancing knowledge about psoriasis and enhancing care of the disease; and the International Federation of Psoriasis Associations (IFPA), a not-for-profit organisation representing psoriasis patients worldwide.
The mission of the GPA is to provide the common benchmark on the complete burden of psoriasis in all countries and regions throughout the world. The GPA will leverage existing data from publications and registries – and additional studies will be commissioned when gaps are identified.
The GPA is a long-term project that seeks to drive continuous improvement in the understanding of psoriasis and to uncover how it affects both the individual and society at large – and will as such play an important part of the overall quest to support research that will someday help researchers find a cause and a cure for psoriasis.
Full thickness skin models from human pluripotent stem cells for identification and testing effectiveness of personalised therapies in atopic dermatitis
Grantee: Dr Dusko Ilic, MD, PhD, Reader in Stem Cell Sciences, Kings College London, Dr Reiko Tanaka, Lecturer, Department of Bioengineering, Imperial College, London, Dr Patrick Harrison, Senior Lecturer, Department of Physiology, University College Cork, Ireland, and Professor Theodora Mauro, MD, Professor of Dermatology, San Francisco Veterans Affairs Medical Center, USA
Amount: DKK 9,980,000
Grant category: Research Grants in open competition
Year: 2016
Geography: Ireland, United Kingdom, USA
This is an exciting project that, with the international group’s extensive research and know-how in mind, has the potential to create an intriguing base for novel personalised treatments for atopic dermatitis (AD). The project moreover holds an innovation potential that may make it stand out in the emerging global bio-economy.
The prevalence of AD, an inflammatory skin disease resulting in itchy, red, swollen and cracked skin, is constantly increasing. Today, it affects 15-30 percent children and 2-10 percent adults worldwide, presenting a significant economic burden to healthcare systems.
There is no cure for AD, only soothing of the symptoms. In the majority of AD patients, the disease is a consequence of a blend of genetic defects of the skin barrier defects and abnormal immune responses influenced by environmental factors.
Until now, the models used to assess the interplay are not particularly predictive. The group behind this project aims to change this by using the latest advances in stem cell science, gene editing and tissue engineering to develop and validate innovative 3D in vitro models of skin – making the models similar to skin in AD patients by emulating full thickness skin of varying barrier integrity; faulty, partially repaired or intact, and immune response composition.
As part of the project, the group will also develop mathematical computer models to accurately address the predictive, prognostic and therapeutic outcome of personalised AD therapy – in order to address co-dependence of the quantitative and qualitative changes in skin barrier and activation of immune cells.
The 3D models will also be made available to test various novel therapeutic approaches for AD treatment in a patient specific manner.
Development and validation of a physiologically-based pharmacokinetic model for dermal absorption
Grantee: Dr. Richard H. Guy, Professor of Pharmaceutical Sciences & Dr. M. Begona Delgado-Charro, Associate Professor of Pharmaceutics, University of Bath
Amount: DKK 3,564,000
Grant category: Research Grants in open competition
Year: 2016
Geography: United Kingdom
The project aims to develop a physiologically based pharmacokinetic model to predict the dermal absorption and disposition of drugs included in complex topical products.
A distinctive feature of the research is the integration of formulation-dependent information derived experimentally, and a deliberate strategy to facilitate the practical implementation of the model for a wide range of drugs.
The long-term goal is to develop a model, which will predict drug absorption and disposition from dermal products thereby facilitating their optimisation and, ultimately, the development of high-performance medicines.
The LEO Foundation Award 2013 – Silver Award
Grantee: Dr. Muzlifah Haniffa
Amount: DKK 500,000
Grant category: LEO Foundation Awards
Year: 2013
Geography: United Kingdom
Presented to Muzlifah Haniffa, Wellcome Trust Clinical Intermediate Fellow in Dermatology at the Institute of Cellular Medicine, Newcastle University, UK.
Dr. Haniffa’s research focuses on dendritic cells; a type of white blood cells also present in the skin that are important in regulating immune responses against microorganisms, cancer and tolerance to self-proteins. Her research has the potential to lead to enhanced vaccination strategies against cancer, such as melanoma, and infections.
Psoriasis and cardiovascular co-morbidity – funding of an overview committee
Grantee: Professor Christopher Griffiths, Faculty of Medical and Human Sciences, University of Manchester
Amount: DKK 900,000
Grant category: Research Grants in open competition
Year: 2012
Geography: United Kingdom
The background to this project – establishing and operating a multidisciplinary international scientific committee on psoriasis and cardiovascular disease (CVD) – is the increased risk of cardiovascular disease and related mortality amongst psoriasis patients.
Research investigating the interface between the two conditions – from epidemiological studies to basic experimental research – may prove key to improving the overall care of psoriasis patients.
Chaired by Professor Christopher Griffiths from the Faculty of Medical and Human Sciences at the University of Manchester in the UK, the committee consists of three dermatologists and three cardiologists, with at least one of each based in the USA.
The committee’s work focuses on:
- How scientific understanding can be improved through new research initiatives
- Building a consensus on biomarkers in research
- The potential relationships between biomarkers and clinical results and the benefits for patients
- Areas of particular interest for further research
- Investigation of cardiovascular side-effects in clinical development projects
The LEO Foundation Award 2008 – Silver Award
Grantee: Dr. William Agace
Amount: DKK 500,000
Grant category: LEO Foundation Awards
Year: 2008
Geography: United Kingdom
Presented to British researcher William Agace. Agace and his research team investigated the underlying control mechanisms for the processes behind the generation and movement of lymphocytes in the intestines, and identified the factors that determine which are activated and where they go in the intestinal system.
Insight gained from William Agace’s research will enable new and more targeted therapies for ailments such as chronic inflammatory bowel disease, a serious disorder with only limited treatment options available today. William Agace earned his MSc at Bristol University in microbiology, and his PhD in immunology from Lund University. In the late 1990’s, he spent three years as a postdoc at Harvard Medical School. In 2006, he was appointed professor of experimental medical research and head of the immunology section at Lund University. He has published more than 35 original articles and several book chapters.