The function and therapeutic potential of miR-146 family in the suppression of Type-2-cell-promoting environment in atopic dermatitis
Grantee: Ana Rebane, PhD, Head of the RNA Biology Research Group, Institute of Biomedicine and translational Medicine, University of Tartu
Amount: DKK 1,650,000
Grant category: Research Grants in open competition
Year: 2017
Geography: Estonia
Atopic dermatitis (AD) develops because of skin barrier abnormalities leading to activation of keratinocytes (KCs) and development of Type-2-cell- mediated chronic skin inflammation.
While the initial molecular events leading to induction of Type-2-cell-promoting cytokines are not well defined, it has been suggested that activation of the NF-kB pathway in response to environmental and/or intrinsic factors in KCs may be at play.
Concurrently, microRNAs – in particular miR-146a and miR-146b (miR-146a/b) – which are post-transcriptional gene expression regulators modulating various biological processes, have been shown to have an anti-inflammatory function in KCs and in the chronic phase of skin inflammation in AD.
In this project, Dr Rebane hypothesizes that miR-146a/b might inhibit AD-promoting events in the skin as these microRNAs act by targeting multiple factors in the NF-κB pathway.
Dr Rebane aims to study this relation using tissue culture and murine models, and assess the therapeutic potential in the regulation of Type-2-cell-promoting cytokines in the development of AD. In addition, it is planned to describe the expression of miR-146a/b isoforms and novel AD associated miRNAs in the skin of AD patients with the aim of detection of novel therapeutic targets.
The spatial composition and distribution of the cutaneous microbiota in atopic dermatitis and healthy skin
Grantee: Professor Thomas Bjarnsholt DMSc, PhD, Costerton Biofilm Center, Department of Immunology and Microbiology, and Department of Clinical Microbiology, University of Copenhagen
Amount: DKK 2,857,565
Grant category: Research Grants in open competition
Year: 2017
Geography: Denmark
In this study, Dr Bjarnsholt looks at skin microbiota and expects to illuminate consistencies and differences between atopic dermatitis and healthy skin. He will do so with focus on the cutaneous microbial composition and spatial distribution in the different layers in AD relative to healthy skin.
The skin microbiota is recognised to significantly impact human health but remains incompletely characterised in the pathogenesis of common cutaneous conditions such as AD. Understanding the three-dimensional distribution of bacteria within the skin may provide relevant insights regarding transition from healthy to diseased skin.
This study will compare the distribution and composition of the commensal, skin microbiota in dry, moist and sebaceous environments as they relate to early onset in AD patients relative to healthy volunteers.
Tape strips and sub-divided skin biopsies will be sampled and analysed by three informative, supplementary methods, i.e. cultivation, Confocal Laser Scanning Microscopy (CLSM) and Next Generation Sequencing (NGS).
This is foreseen to show how the microbiota changes in immediately adjacent regions of tissue among diseased and healthy individuals. In addition, generation of high-resolution, 3D images by confocal microscopy will allow visualisation and confirmation of the molecular and culture results.
The LEO Foundation Award 2016 – Silver Award
Grantee: Dr. Thomas Wiesner
Amount: DKK 500,000
Grant category: LEO Foundation Awards
Year: 2016
Geography: Austria
Presented to Dr. Thomas Wiesner. Dr. Wiesner is breaking new ground to find new mechanism-based cancer therapies. Following medical school, Dr. Wiesner wrote his thesis on the genomic aberrations of cutaneous lymphoma and completed his residency in dermatology at the Medical University of Graz in Austria. Dr. Wiesner spent five years conducting basic and translational research using cutting-edge techniques within high-throughput sequencing techniques in particular. His work within skin cancer research resulted in key discoveries, in particular concerning the genomic landscape of skin tumours.
Based on his experience as a physician-scientist and his access to high-quality clinical samples, Dr. Wiesner plans to combine high-throughput sequencing technologies, computational approaches and functional assays in order to define the relevant genomic and epigenomic aberrations in skin cancer and pave the way for new mechanism-based cancer therapies.
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.
The LEO Foundation Award 2016 – Silver Award to young scientist in Japan
Grantee: Dr. Yu Sawada, research fellow, Department of Dermatology, Kyoto University and assistant professor, University of Environmental and Medical Health, Kitakyushu
Amount: DKK 250,000
Grant category: LEO Foundation Awards
Year: 2016
Geography: Japan
The LEO Foundation has offered the LEO Foundation Silver Award 2016 to Yu Sawada for his pioneering dermatological research. The award has been bestowed in collaboration with the Japanese Society for Investigative Dermatology (JSID).
The award ceremony took place in Sendai, Japan, at the 41st annual conference of JSID on 11 December 2016.
Dr. Yu Sawada currently holds the position as a research fellow at the Department of Dermatology in Kyoto University and assistant professor at the University of Environmental and Medical Health in Kitakyushu. Dr. Sawada’s research focuses on establishing and implementing a new therapeutic paradigm for the improvement of inflammatory skin diseases through medical treatment in combination with specific lifestyle alterations such as diet, sleep and physical exercise.
The LEO Foundation Award 2016 – Gold Award to young scientist in Japan
Grantee: Dr. Ayumi Yoshizaki, lecturer and independent researcher, Department of Dermatology, Graduate School of Medicine, The University of Tokyo
Amount: DKK 500,000
Grant category: LEO Foundation Awards
Year: 2016
Geography: Japan
The LEO Foundation has offered the LEO Foundation Gold Award 2016 to Ayumi Yoshizaki for his pioneering dermatological research. The award has been bestowed in collaboration the Japanese Society for Investigative Dermatology (JSID).
The award ceremony took place in Sendai, Japan, at the 41st annual conference of JSID on 11 December 2016.
Dr. Ayumi Yoshizaki is a lecturer and an independent researcher in the field of dermatological autoimmune diseases based at Department of Dermatology, Graduate School of Medicine, The University of Tokyo. Dr. Yoshizaki has his own research group, an impressive list of publications and is well acknowledged by the Japanese dermatological and scientific communities. His future research is focused on autoimmune diseases related to the skin, particularly systemic sclerosis (SSc). His lab uses highly innovative techniques to explore the role of auto-reactive B cells in SSc at the single cell level. He is a rising star that very well could establish himself as a leader in his field globally.
Influence of microbes on development of skin diseases
Grantee: Anders Johannes Hansen, PhD, Associate Professor, University of Copenhagen, Denmark, Robert Gniadecki, MD, Professor, Dermatology Department, Bispebjerg Hospital, Copenhagen, Denmark, Kim Holmstrøm, R&D Manager, Department of Biomedical Technology, Bioneer A/S, and Nicola Segata, PhD, Assistant Professor and Principal Investigator, Computational Metagenomics, CIBIO, University of Trento, Italy
Amount: DKK 5,035,000
Grant category: Research Grants in open competition
Year: 2016
Geography: Denmark, Italy
By combining new data from the human skin microbiome with existing knowledge of pathophysiology and clinical phenotypes of Atopic Dermatitis, AD, Actinic Keratosis, AK and non-melanoma skin cancer, the team will seek to establish a novel understanding of these diseases.
Recent microbiome analyses have revealed that mammalian body surfaces are colonized by vast numbers of bacterial communities, which motivates the exploration of the role of the microbiota in normal and diseased skin. There are indications that the skin microbiome plays a key role in both inflammatory skin disease and non-melanoma skin cancer.
The vision for the team’s research endeavours is to explore the microbiome for the identification of new targets for treatment, and for the development of improved treatment modalities for patients with AD, AK and non-melanoma skin cancer.
The team’s explorations will potentially also lead to the development of better and more specific and sensitive diagnostic and prognostic methods for monitoring skin disease.
The Danish-Italian team will work from a unique microbiome discovery platform established at the University of Copenhagen (UCPH) within the GenomeDenmark Cancer & Pathogen project. The platform utilizes procedures enriching various types of microbes combined with state of the art DNA and RNA sequencing and bioinformatics data analysis.
Skin barrier dysfunction and thymus size during the first year of life as predictors for atopic dermatitis
Grantee: Jacob P. Thyssen MD PhD DmSci, Trine Danvad Nilausen MD, Lone Skov MD PhD DmSci, Dep. Dermatology and Allergology, Herlev-Gentofte Hospital, Hellerup, Denmark, Caroline Ewertsen MD PhD, Department of Radiology, Rigshospitalet, Copenhagen, Denmark, Charlotte Bonefeld PhD, Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, Pal Szecsi MD DmSci, Department of Clinical Biochemistry, Herlev-Gentofte Hospital, Hellerup , Denmark, Sanja Kezic PhD, Coronel Institute, AMC, University of Amsterdam, The Netherlands, and Christoph Riethmüller PhD, nAnostic Institute, Centre for Nanotechnology, University of Münster, Germany
Amount: DKK 2,558,500
Grant category: Research Grants in open competition
Year: 2016
Geography: Denmark, Germany, Netherlands
The study is foreseen to increase the understanding of the skin barrier and immune system in atopic dermatitis.
Through international collaboration with scientists who perform state of the art and pioneering analyses on skin samples as well as national collaboration with immunologists and radiologists, the team will seek to evaluate non-invasive and easily collectable biomarkers that can predict the risk for atopic dermatitis.
The study has the potential to provide insight in atopic dermatitis pathogenesis and the value of promising pre-atopic dermatitis biomarkers that indicate both inflammation and skin barrier barriers dysfunction. This could be used to develop an algorithm that can better predict the onset of atopic dermatitis.
The team’s work may thus substantially increase the understanding of skin biology in neonates, both normal and diseased. The study will also provide a basis for not only future large-scale observational studies, but also randomised controlled studies evaluating the efficacy of preventive skin barrier restoration or anti-inflammatory treatment in selected groups, potentially reducing the incidence and complications of the most common skin disease in childhood.
The Human Skin Immune Atlas: Three-dimensional reconstruction of serial histology and computational image analysis of dermal immune populations in normal and diseased skin
Grantee: Philip L. Tong, PhD, Department of Dermatology, Royal Prince Albert Hospital, University of Sydney, Australia, Dr Ben Roediger and Professor Wolgang Weninger, Centenary Institute, Newtown, Australia, and Dr Weimiao Yu, Institute of Molecular and Cell Biology, A*STAR, Singapore
Amount: DKK 708,500
Grant category: Research Grants in open competition
Year: 2016
Geography: Australia, Singapore
This research project, led by Dr Philip Tong from the University of Sydney, has the potential to represent a technological advancement in the field of human skin immunological research. By use of 3D histological reconstruction and computational image analysis, the aim is to develop the world’s first Human Skin Immune Atlas of dermal immune populations in normal and diseased skin.
The members of the team assembled for this project are already established experts in the fields of skin immunology, microscopy, inflammation and computational analysis, and the project will have an international platform with sites across Asia and Oceania.
The skin is a complex organ, wherein topographical and micro-compartmental specialisation of the immune system has been demonstrated. The general spatial understanding of the skin immune system has been advanced through the use of transgenic laboratory animals with live imaging tools. These, however, have yet to be validated in humans. The work realised in this project may provide fundamental insights into the human skin immune system.
Moreover, the data generated may have wide reaching implications for the development of better in vitro skin substitutes, validation of in vivo microscopic skin imaging tools for human use and improved quantification of skin inflammation in clinical trial settings.
Skin and blood biomarkers of atopic dermatitis in different paediatric age groups
Grantee: Dr Emma Guttmann, Icahn School of Medicine at Mount Sinai, New York
Amount: DKK 11,500,000
Grant category: Research Grants in open competition
Year: 2016
Geography: USA
Atopic dermatitis (AD), or atopic eczema, is the world’s most common inflammatory skin disorder. Its prevalence has increased during the past few decades and can now be found to be more than 20% in children and 10% in adults.
For children, there is an unmet need for improved therapy for moderate to severe AD and it is likely that therapeutics with proven safety and efficacy in adults will move towards to trials in children. There are, however, when gauging the pathogenesis and characteristic biomarkers related to AD, significant differences between children and adults.
Dr. Guttmann’s study purports to shed light on these differences to enlarge the understanding of biomarkers and to clarify when children transition to the adult biomarker pattern that predicts responses. Correlating the validity of biomarkers in adults with AD vs. different age groups of children and adolescents with AD (including 5-12 and 12-17 years olds) is a critical step before engaging in large clinical trials.
Given the challenge in obtaining biopsies from children during clinical trials, defining a set of biomarkers in blood will prove extremely valuable in these large patient populations. More specifically, the study will address the following questions:
- What are the cutaneous biomarkers in AD in children and adolescents of different age groups and how do these compare with disease activity, epidermal barrier function, and known biomarkers in both infancy/early childhood and adult AD skin?
- Are there useful biomarkers in the blood of children and adolescents with AD that compare well with skin immune and barrier biomarkers, and could these enable a less invasive means to follow biomarker changes and direct skin therapy than skin biopsies?
- At what age do children acquire an “adult” AD phenotype?