Melanocyte stress response pathways and their role in the onset of vitiligo
Grantee: Prashiela Manga, PhD , Associate Professor Dermatology and Cell Biology, New York University School of Medicine
Amount: DKK 5,037,192
Grant category: Research Grants in open competition
Year: 2016
Geography: USA
Vitiligo, an acquired skin disease in which pigment cells, melanocytes, are destroyed, affects 1-2% of people worldwide. The disease deprives the skin of photoprotection leaving it more susceptible to solar damage and compromised cutaneous immunity – and the disease impacts physical and mental health.
Vitiligo is thought to occur in genetically susceptible individuals after being exposed to environmental triggers. Some individuals develop contact vitiligo after direct exposure to certain chemicals. As disease progression in vitiligo is independent from initiating factors, this subset of individuals makes it possible to study vitiligo at large.
The hypothesis in this project is that melanocytes from healthy individuals can withstand exposure to triggers by initiating a stress response regimen that allows the cell to return to homeostasis. These pathways may be disrupted in individuals who develop vitiligo, leaving melanocytes stressed following challenge, causing them to be targeted for removal by the immune system.
In order to investigate this hypothesis, the project will investigate survival pathways in melanocytes cultured from biopsies taken from pigmented skin from individuals who have developed vitiligo.
Development and validation of scoring systems for outcome measures of vitiligo: an international cooperative initiative
Grantee: Professor, Dr Nanja van Geel, Department of Dermatology, Ghent University Hospital, Ghent
Amount: DKK 735,000
Grant category: Research Grants in open competition
Year: 2016
Geography: Belgium
Clinical trials for vitiligo – a skin disease that causes loss of skin color in blotches – lack uniformity in reported outcomes and the measurements hereof. This lack of uniformity hampers development of general treatment guidelines, as it limits appropriate interpretation and comparison of results. In particular, since vitiligo is without biomarkers, clinical measurement tools are crucial to assess disease extent.
A recently introduced scoring instrument, Vitiligo Extent Score (VES), will play a central role in this international project. The project team comprises researchers from Belgium, Netherlands, France, Italy, and the UK, and their aim is to create a worldwide consensus on measuring disease severity.
The VES was designed to be intuitive, fast and accurate, and the team has successfully performed an initial validation for estimating global disease extent. The aim of this project is to further develop and validate reliable and feasible instruments to assess vitiligo status in order to improve evidence-based therapeutic decisions and develop novel treatments.
Hereafter, the tool will be used for the development of other scoring methods including a patient-reported outcome measure, a physician global assessment, a vitiligo disease activity score, and a digital image analysis system for target lesions.
International Eczema Council
Grantee: Amy Paller, MS, MD, IEC President, Professor of Dermatology and Professor of Pediatrics, Northwestern University’s Feinberg School of Medicine, Chicago, and Emma Guttman-Yassky, MD, PhD, IEC President-Elect, Associate Professor of Dermatology & Immunology, Department of Dermatology, Icahn School of Medicine, Mount Sinai, New York
Amount: DKK 340,000
Grant category: Research Grants in open competition
Year: 2016
Geography: USA
The IEC is convening a meeting at the ESDR in September 2015 to write a position paper on Atopic Dermatitis as a systemic disease.
In March 2016, the IEC will hold a session at the Annual AAD in Washington, D.C. focusing on AD phenotyping – starting to use biomarkers to assess subgroups of AD, which may be relevant to the understanding of disease and treatment decision-making.
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 natural history of skin cancer formation: from normal skin to cancer
Grantee: Associate Professor Kiarash Khosrotehrani, University of Queensland
Amount: AUD 268,239
Grant category: Research Grants in open competition
Year: 2015
Geography: Australia
Associate Professor Kiarash Khosrotehrani from The University of Queensland leads a team that has hypothesized that upon UV irradiation and acquisitions of mutations, only epidermal cells that can rapidly proliferate are likely to give rise to pre-cancerous and cancerous lesions.
This hypothesis will be tested using multicolour lineage tracing to follow simultaneously multiple epidermal clones that will further be microdissected to establish their mutational profile. This study has the potential to fundamentally change our understanding of field cancerisation, cell of origin of squamous cell cancer establishing potentially new therapeutic targets.
Preventing Basal Cell Carcinoma formation by targeting the tumor environment
Grantee: Associate Professor Kiarash Khosrotehrani, University of Queensland
Amount: AUD 415,386
Grant category: Research Grants in open competition
Year: 2015
Geography: Australia
In this study, Associate Professor Kiarash Khosrotehrani of The University of Queensland in Australia proposes to better characterise the molecular nature of the factors provided by fibroblasts to support basal cell carcinoma (BCC) growth in vivo in order to find new targets for therapies that would prevent BCC development. He and his team will also show proof of principle demonstrating that targeting this process can actually prevent BCC development.
These findings have the potential to translate in effective prevention strategies, allowing field therapy of normal looking skin to avoid the development of new BCCs. Such finding will have strong health benefits in terms of morbidity associated with multiple surgeries, years of healthy life enjoyed by individuals and finally in terms of economic cost.
Young Scientists
Grantee: Mikkel Bohm, Young Scientists (Astra)
Amount: DKK 3,000,000
Grant category: Research Grants in open competition
Year: 2015
Geography: Denmark
The talent competition, Young Scientists, is developing talents in both kids and young people in science.
It is believed that science is a powerful tool to understand and change the world for the better. The competition’s aim is to contribute to society in a meaningful way by inspiring a new generation and giving them engaging experiences with science.
The LEO Foundation has found this work important and supports the competition over three years.
Psoriasis in children
Grantee: Professor Lone Skov, Department of Dermato-Allergology, Gentofte Hospital
Amount: DKK 4,500,000
Grant category: Research Grants in open competition
Year: 2014
Geography: Denmark
Psoriasis is a chronic inflammatory skin condition with a prevalence of 2-3% in northern Europe. While considerable research exists on adults with psoriasis, there is little research on the condition in children. Identifying key factors associated with psoriasis in childhood may lead to more effective control and possibly even prevention of the condition.
The study aims to determine environmental and genetic risk factors relating to the development of psoriasis in children, the nature of stress related to the child and family, and quality of life. The project also aims to determine the link with risk factors of co-morbidity and the effect of early intensive treatment.
The study is led by Professor Lone Skov, Department of Dermato-Allergology, Gentofte Hospital, Denmark. The team will explore the following hypotheses:
- Risk factors for early onset of psoriasis can be predicted
- Early debut of psoriasis has a significant impact on quality of life and individual and family-related stress
- Early intensive treatment leads to remission
- There is already an increased risk of co-morbidity in children with psoriasis
- Age at debut, risk factors and co-morbidity are related
to the genetic risk.
The study offers a unique possibility to access data from children with psoriasis shortly after diagnosis, which in turn can pave the way for new and improved tools for assessing the impact of the condition on quality of life in a well-controlled study design.
Identification and Characterization of Key Itch Mediators and Receptors in Human Pruitus
Grantee: Professor Martin Steinhoff, University of California San Francisco
Amount: USD 388,225
Grant category: Research Grants in open competition
Year: 2013
Geography: USA
Itch is probably the most common symptom in dermatology and it is associated with a significant impact on the patient’s life.
A team led by Professor Martin Steinhoff, University of California San Francisco, has set out to develop novel targeted therapies for chronic itch in humans.
Besides the lesional and non-lesional as compared to healthy skin, the project team will also identify critical itch mediators and/or receptors that are expressed (and activated) in human dorsal root ganglion (DRG) and spinal cord tissue. To address this, mediators will be identified as well as receptors associated with human itch, and thereby the team will be able to define “biomarkers” for the different pruritic human diseases.
The project will be the first-of-a-kind study to analyse the expression and distribution of key itch mediators and receptors in human skin, human DRG and human spinal cord, and will therefore provide a significant basis for future translational research that targets these mediators/receptors in the different subtypes of itch.
Moreover, it is the first time that it will be tested whether several new itch pathways that have been described in murine skin models are relevant, i.e. can be translated, in human disease state.
Care for chronic skin diseases with a patient-centric approach
Grantee: Professor Lieve Brochez, University of Ghent
Amount: EUR 330,000
Grant category: Research Grants in open competition
Year: 2013
Geography: Belgium
Skin cancer is currently the most frequent type of cancer. At present, life-time risk is estimated at one in six and, with an ageing population, this is expected to increase even more. It is assumed that early detection allows better cure rates and more cost-effective treatment, and skin cancer thus seems suitable for screening initiatives. However, questions remain about the cost–benefit ratio.
This study is led by Professor Lieve Brochez of the University of Ghent, Belgium. It aims to calculate the actual cost of skin cancer in Belgium, the expected cost with an ageing population and how much early detection of skin cancer could affect these costs.
The team will use the results to develop an internationally applicable health-economic model. The model will allow other European countries to use local data, enabling data to be compared across Europe.
Secondly, the study will evaluate a new skin cancer screening approach to compare the yield of this type of screening to the yield of systematic screening in an asymptomatic population within a well-defined population.
Quality of life will be assessed for all screened persons with skin cancer and/or actinic keratosis in order to generate patient-centric data to evaluate the burden of skin cancer.