Beneficiaries: Dr. Richard H. Guy, Professor of Pharmaceutical Sciences & Dr. M. Begona Delgado-Charro, Associate Professor of Pharmaceutics, University of Bath, UK

Grant: DKK 3,564,000

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.

Beneficiaries: Amy Paller, MS, MD, IEC President, Professor of Dermatology and Professor of Pediatrics, Northwestern University’s Feinberg School of Medicine, Chicago, IL, USA, 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, NY, USA

Grant: DKK 340,000

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.

Beneficiary: Professor, Dr Nanja van Geel, Department of Dermatology, Ghent University Hospital, Ghent, Belgium

Grant: DKK 735,000

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.

Beneficiary: Prashiela Manga, PhD
, Associate Professor Dermatology and Cell Biology, New York University School of Medicine, USA

Grant: DKK 5,037,192

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.

Beneficiary: Astra, the national Centre for Learning in Science, Technology and Health in Denmark, Copenhagen

Grant: 2,000,000 DKK

Denmark’s largest science conference, the Big Bang Conference, has received two million Danish kroner over the next three years from the LEO Foundation.

Big Bang is the largest Danish science conference and exhibition targeted all who teaches, facilitates or researches in the science and science fields – in primary and secondary schools and higher education.

The conference, held once a year, gathers more than 1,000 people for two involving and inspiring days with relevant keynote speakers, a humming exhibition atmosphere, involving workshops and novel ideas for the continued renewal of science education.

The conference is held next on 23 and 24th March 2017 in Odense Congress Center, Denmark.

www.bigbangkonferencen.dk

Beneficiaries: 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

Grant: 9,980,000 DKK

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.

Beneficiaries: Prof. Catharina (Carien) Maria Niessen, Department of Dermatology, University of Cologne, Germany; and Brenda Figueroa, Gordon Research Conferences, West Kingston, Rhode Island, USA

Grant: DKK 149,099

The 2017 Gordon Research Conference on Epithelial Differentiation and Keratinization (GRC-EDK), to be held May 6-12 in Italy, is the premier international meeting in epithelial biology.

It has been held biennially since 1979 with attendance from leading epithelial biology researchers, leaders from other fields, and early career scientists with innovative and exciting research programs to present and promote the latest conceptual, translational and technological advances in epithelial biology.

Today, the meetings take on stem cell biology, regenerative medicine, inflammatory skin diseases, skin cancer, epigenetics, and global genomics, and the program moreover explores developments in gene therapy, genome organisation, cell competition, stress responses as well as cutting edge advances in intravital imaging.

A third of the speakers are from outside the area in order to fuel new concepts and promote discussion of novel ideas, and more than a third of the oral presentations come from submitted abstracts to accommodate late breaking exciting stories and ensure speaking opportunities for young investigators.

To promote collaboration between academic medicine and industry the meeting also invites speakers from biotech and other academic scientists with strong industrial ties. Finally, the meeting will continue the commitment to trainee mentorship, including a career mentoring panel discussion with special emphases on careers in academia versus industry, and the importance of diversity within science.

Link to the meeting homepage.

Beneficiary: Kevin Grimes, Director, SPARK Programme, Associate Professor, Chemical and Systems Biology, Stanford University, California, USA

Grant: DKK 4,500,000

Bridging the gap between early research and clinical development is a challenging endeavour. There is an inherent risk that early-stage programs will fail during development, no matter how promising the science is.

Such nascent programs are unlikely to attract interest from industry until they have reached significant milestones, and very little funding is available from the NIH, foundations, or private enterprise for this critical transition.

The LEO Foundation SPARK donations at Stanford will help incubate and accelerate dermatology projects. SPARK is a unique partnership between university and industry targeted advancement of Stanford research towards development of new breakthrough therapies. SPARK provides access to specialised knowledge and technical expertise regarding drug and diagnostic development, dedicated core laboratory facilities, and sources of funding to support translational efforts.

The donations will be awarded as a supplement to the existing suite of support and funding from Stanford and will ensure that as many as 15 Stanford dermatology projects will be progressed towards human proof of concept.

It is expected that the grant will foster a renewed and unique focus on dermatology at Stanford University and enable a larger number of orphan drug research projects to reach actual clinical development.

The grant from the LEO Foundation is paid out in three equal portions in 2016, 2017 and 2018.

Learn more about the SPARK Program at Stanford University here.

Beneficiaries: 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

Grant: DKK 6,370,000

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.

Beneficiary: Dr Cord Brakebusch, Professor, Section of Molecular Pathology, BRIC, Department of Biomedical Sciences, University of Copenhagen

Grant: DKK 2,140,000

This study seeks new targets to reduce the formation of psoriatic lesions. A novel epigenetic mechanism, which is known to induce IL-23 in psoriasis, is also found in non-lesioned skin and may hold promise.

Psoriasis is a chronic inflammatory skin disease that involves a complex crosstalk between immune cells and skin cells (keratinocytes). While the etiology of psoriasis is basically unknown, many researchers have gauged the elements of this crosstalk – in many models. During this work, they have shown that there are multiple different, yet intertwining mechanisms underlying the disease.

One is that monoclonal antibodies that target the IL-23/IL-17 immune axis have demonstrated impressive clinical efficacy in patients with moderate-severe psoriasis. There are however, still many missing pieces of the puzzle to fully understand how this disease initiates and develops.

Dr Cord Brakebusch’s team has demonstrated that keratinocyte-derived IL-23 is sufficient to cause chronic skin inflammation in mice. Furthermore, they have elucidated an epigenetic mechanism which controls IL-23 expression and it is explained that the epigenetic control mechanism has been shown not just in active psoriasis lesions, but also, albeit to a lesser extent, in normal-appearing skin of psoriasis patients.

This suggests that the epigenetic alterations might precede the development of psoriasis lesions, and the team now wants to identify and validate targets for small molecule drugs that may prevent excessive IL-23 expression by keratinocytes through this epigenetic mechanism.

As a long-term goal for the study and its potential findings Dr Brakebusch and his team hope that topically administrated small molecular weight inhibitors could prevent excessive IL-23 production by keratinocytes – and ultimately aim at reducing the formation of psoriatic lesions.

Beneficiaries: Dr. Ayumi Yoshizaki, lecturer and independent researcher, Department of Dermatology, Graduate School of Medicine, The University of Tokyo & Dr. Yu Sawada, research fellow, Department of Dermatology, Kyoto University and assistant professor, University of Environmental and Medical Health, Kitakyushu

Grants: DKK 500,000 & DKK 250,000

The LEO Foundation has offered “LEO Foundation Awards 2016 in association with JSID” to two young, promising Japanese scientists for their pioneering dermatological research. The awards have been bestowed in collaboration with the Japanese Society for Investigative Dermatology (JSID).

The LEO Foundation Gold Award of DKK 500,000 went to Dr. Ayumi Yoshizaki, and the DKK 250,000 Silver Award went to Dr. Yu Sawada. The award ceremony took place in Sendai, Japan, at the 41st annual conference of JSID on 11 December 2016.

About the awardees

Gold award winner: 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.

Silver award winner: 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.

Beneficiary: Vasileios Bekiaris, Ph.D., Associate Professor, Section for Immunology and Vaccinology, National Veterinary Institute, Danish Technical University, Denmark

Grant: DKK 1,047,816

Psoriasis and most autoimmune diseases are characterised by a deregulated hyper activation of T cells leading to chronic tissue destruction and in many cases significant morbidity. Immune checkpoint receptors (ICRs) negatively regulate the immune system by dampening lymphocyte functionality.

Bekiaris and his team have, as have others, shown that manipulation of these ICRs can alter the outcome of the immune response; a strategy currently successful in cancer immunotherapy.

In this project the team will use the mouse psoriasis-model (IMQ) to test the hypothesis that in vivo activation of specific ICRs will block the induction and progression of psoriasis. In addition, the team aims to characterise the importance of ICR signalling during the course of psoriasis, both at the cellular and molecular levels.

The study will delineate the molecular mechanisms underlying ICR signalling during skin inflammation and potentially create a new pathway for possible future treatment of psoriasis though opening of new targets.

Beneficiary: Charlotte Menné Bonefeld, Associated Professor, Department of Immunology and Microbiology, University of Copenhagen, Denmark

Grant: 2.385.900 DKK

The skin provides the first barrier of defence between the body and the environment. It is one of the largest organs of the human body and is constantly being exposed to pathogens and environmental triggers.

The outermost layer of the skin is the epidermis and it consists of a variety of both immune and non-immune cell types. Among the immune cells within epidermis are the T cells. One of the important characteristics of T cells is that they can develop into memory T cells following their activation.

Experimental work is often done with mice, but experience shows that there is difference between T cells in humans and mice epidermis – a difference that until recently has been thought related to species diversity.

Recent findings, however, have shown that environmental triggering factors, such as microorganisms or chemical irritants, lead to a dynamic shaping of the type of T cells present in the epidermis. Based on these discoveries, the team led by Charlotte Menné Bonefeld has hypothesised that the difference between T cells in human and mice epidermis are not mediated by species differences, but rather by difference in skin exposure to microorganisms and chemicals that occurs early and throughout the whole life.

Therefore, the team will investigate i) the similarities and differences of T cells in human and mice epidermis, ii) the effect of allergen and infection agents on the phenotype and activity of epidermal T cells and iii) the interplay between epidermal immune cells forming the immunological barrier properties of the skin.

Answering these questions will be crucial for developing better treatments for inflammatory skin diseases as it is very likely that these mechanisms play a central role in the pathogenesis of several inflammatory skin diseases like allergic contact dermatitis, atopic dermatitis and psoriasis.

Beneficiary: Luis Garza, Department of Dermatology, Johns Hopkins School of Medicine, Baltimore, MD, USA

Grant: DKK 330,000

Rosacea affects many people around the globe and treatments could be better and more efficient. Defining new possible treatments will not only satisfy this clinical need, but also offer the opportunity to learn about the pathogenesis of rosacea and subsequent basic knowledge about skin biology.

The discovery of the role of the innate immunity in rosacea has generated many interesting new avenues for investigation.

The team led by Luis Garza points to the fundamental role of keratinocytes in disease pathogenesis as a critical insight given that keratinocytes, more than fibroblasts for example, contribute to innate immunity pathways.

This, they say, begs an interesting question: if keratinocyte turnover is so rapid such that entirely new cells are present every several months, how is the propensity for rosacea so robustly inherited from ‘mother’ to ‘daughter’ keratinocyte?

The team hypothesises that epigenetic lesions are more likely to explain the mostly adulthood acquisition of rosacea and the stability of disease in adulthood rather than DNA mutations. With this project, the team has the potential to generate data that can be used in academics and industry to measure improvements and severity of rosacea through its epigenetic profile.

Beneficiary: Dr Koichi Suzuki, PhD, Professor, Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Japan

Grant: DKK 460,000

Release of double-stranded (ds)DNA from keratinocytes has been linked to the initiation of psoriasis via induction of an immune response. Furthermore, vitamin D has been reported to interfere with this mechanism. Vitamin D analogues are widely used for treatment of psoriasis and have a well-known effect on keratinocyte proliferation and differentiation.

Dr Koichi Suzuki and his Japanese-Chinese team hypothesise that the release of dsDNA may more directly induce the characteristic hyper-proliferation and abnormal differentiation of keratinocytes seen in psoriasis by a TNFα-mediated inflammatory process in keratinocytes.

The team will investigate this hypothesis and the impact of vitamin D by the use of keratinocyte cultures and psoriasis skin samples from patients treated with a vitamin D analogue.

The project may further enhance our understanding of the complex molecular events underlying psoriasis and how vitamin D treatment may intervene in the pathogenic process, potentially revealing new aspects of the mode of action of vitamin D.

Beneficiaries: Joel Dudley, PhD, Director of Biomedical informatics, Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York, USA, and Peter Riis Hansen, MD, DMSc, PhD, Consultant (invasive cardiology), Associate Professor, Department of Cardiology, Gentofte Hospital, University of Copenhagen, Denmark

Grant: DKK 13,100,000

Cardiovascular diseases (CVD), such as myocardial infarction and stroke, are leading causes of death globally. Independent of traditional risk factors, however, psoriasis patients run an increased risk of CVD, adding considerably to morbidity and mortality for this large patient group.

“Inflammation has been proposed as a part of the explanation for the association between psoriasis and CVD. However, when we look at the underlying pathophysiology and molecular drivers of this connection, they are unclear. It is also unresolved whether treatment responses for psoriasis alter the course of CVD. To us, this suggests that the connection with inflammation might be more complex than currently appreciated,” said Joel Dudley, Director of Biomedical informatics at Icahn School of Medicine, Mount Sinai in New York.

Together with Peter Riis Hansen, Department of Cardiology, Gentofte Hospital, University of Copenhagen, Denmark, Dudley will lead a team focused on developing a much needed understanding between the molecular mechanisms of psoriasis and the increase in CVD comorbidity. Understanding these complex interactions between skin and cardiovascular health will lead to insights for future preventive treatments and improved prognosis.

The team will employ an array of modern high throughput technologies to bring together information about genetics, immunology, local gene expression, microbiomes, and more standard clinical measures to develop an unprecedented map of factors impacting cardiovascular health in psoriatic patients.

“We will apply sophisticated bioinformatics and network biology techniques to integrate the data and develop a disease network model that will enable both discovery and testing of novel hypotheses concerning biomarkers and pathogenic mechanisms. We believe that this disease network model will serve as a powerful and unprecedented resource for the dermatology, cardiology, and immunology research communities,” said Peter Riis Hansen.

More specifically, the model may facilitate the re-interpretation of data from previous studies and clinical trials, be queried by scientific and clinical investigators to evaluate novel clinical and molecular hypotheses, and inform new understanding of fundamental molecular mechanisms underlying the interplay between skin biology, immune function, and the immune-metabolic-cardiovascular axis.

The resulting disease network model may also uncover molecular mechanisms contributing to increased CVD risk in other immune disorders, such as rheumatoid arthritis, atopic dermatitis, and inflammatory bowel disease.

“We believe that the data generation activities alone would provide tremendous value to the research community, and that developments in data analysis and bioinformatics has the potential to increase exponentially our understanding of molecular mechanisms underlying CVD risk in inflammatory skin disease,” said Peter Riis Hansen.

Beneficiaries: Joel Dudley, PhD, Director of Biomedical informatics, Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York, USA, and Jeanne Duus Johansen, MD, DMSc, Director National Allergy Research Centre, Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Denmark

Grant: DKK 11,100,000

Atopic dermatitis (AD) and hand dermatitis are heterogeneous disease entities and there has yet to be developed a good understanding of their many different clinical aspects. Thus it remains extremely challenging to provide patients with better treatment outcomes and prognosis.

A newly formed team of scientists at Gentofte Hospital in Copenhagen and Mount Sinai in New York has set out to change this.

“Next generation sequencing and advanced bioinformatics technologies give us powerful new opportunities to explore and understand the molecular pathophysiology of atopic dermatitis and hand dermatitis,” said Dr. Joel Dudley, Director of Biomedical informatics at Icahn School of Medicine, Mount Sinai in New York.

“It is a study that has not previously been performed, and we expect to make a breakthrough in the understanding, classification and treatment of these skin diseases. We hope to improve our knowledge and understanding of the molecular basis of atopic dermatitis and hand dermatitis and their relation to clinical features. Consequently, we also hope to pave the way for improved opportunities for managing and preventing disease,” said Dr. Jeanne Duus Johansen from the Department of Dermato-Allergology at Gentofte Hospital.

She and Joel Dudley will lead a trans-Atlantic team of researchers working with high-throughput, genome-wide profiling of multiple of the ‘–omics’ modalities, including genome, transcriptome, epigenome, and microbiome.

The goal is to develop a deeper understanding of how the molecular manifestation of the heterogeneous diseases correlates with clinical variables such as onset of disease and treatment outcomes. The technologies employed by the team can provide comprehensive molecular profiles that can enhance the understanding of the system-wide mechanics and properties of complex biological systems.

Dudley’s team will integrate the ‘-omics’ data sets to clarify the complex biological mechanisms underlying disease. They will do so by connecting molecular profiles with clinical data to identify molecular surrogates of drivers of important clinical features of disease.

The study will build on previous efforts to assemble and characterise a Danish cohort of individuals affected by AD in adulthood and/or hand dermatitis. The proposed study will add important new dimensions of molecular information that will enable new insights into molecular mechanisms and features of disease. Furthermore, the team sees that an incorporation of molecular measures, namely microbiome and epigenome, may offer insight into environmental correlates or determinants of disease.

Finally, the team foresees that the data and results generated may serve as an important new asset to the AD and dermatology research communities.

“We believe that the data and results generated by our study will enable new research directions and insights into AD and dermatological disease. Furthermore, we believe that such future insights would be enabled by the unique availability of the proposed comprehensive multi-omics data set integrated with comprehensive clinical data and assessment of a large patient cohort,” said Dr. Jeanne Duus Johansen.

Beneficiary: Igor Vujic, MD, Assistant Professor, Sigmund Freud University & Department of Dermatology, Rudolfstiftung Hospital, Vienna, Austria

Grant: DKK 265,000

The Austrian-American team behind the study, led by Dr. Igor Vujic, aims at identifying more specific and sensitive biomarkers in order to better detect and monitor progression of malignant melanoma – a common and deadly skin cancer that is difficult to treat, and that accounts for numerous deaths each year.

In the clinic, physicians face two main problems around malignant melanoma: detection of early disease, and monitoring of disease progression, recurrence and its response to therapies. The existing melanoma biomarkers are not very specific and only rarely help.

Melanoma cells, however, produce a specific set of RNA molecules of which some are excreted and found in the blood stream – ready for identification and use as biomarkers. Recent technical advances make it possible to extract and analyse serum RNA and identify the cell of origin.

The team will mainly concentrate on non-coding RNAs, a new class of molecules known to be very specific for certain diseases such as cancer. Preliminary studies have identified and confirmed 237 interesting candidates through RNA-Seq TCGA (The Cancer Genome Atlas) data.

In the course of the study, the team will perform RNA-Seq studies on serum samples from melanoma patients and healthy individuals to find differences in RNA quality and quantity to be used as melanoma serum-markers. The team will moreover test changes of the amount of these specific RNA molecules in melanoma patients over time to discover if they can be used as disease progression biomarkers.

Beneficiaries: Douglas E. Brash, PhD, Professor, Departments Therapeutic Radiology and Dermatology, Yale School of Medicine, New Haven, CT, USA, and Etelvino Bechara, PhD, Professor, Institute of Chemistry, University Sao Paulo & Federal University, Sao Paulo, Brazil

Grant: DKK 281,000

The LEO Foundation has granted support to a conference on chemiexcitation in human disease to be held at the Cold Spring Harbor Laboratory, Long Island, NY. The initiative will bring together a select group of internationally renowned scientists with the goal of combining expertise from several fields to explore the ramifications of a previously unrecognized mode of disease – chemical excitation of electrons (“chemiexcitation”).

Chemiexcitation is a high-energy biophysical process that underlies bioluminescence, but it had not been observed in mammals until a finding that chemiexcitation sent melanocytes down the path to melanoma when two key enzymes were activated by ultraviolet light.

The insight driving the conference is that the same chemistry will occur wherever nitric oxide, superoxide, and melanin are present at the same time, so chemiexcitation may also be a hidden step in diseases where sunlight is not involved.

The three chemical reactants co-occur during inflammation and ischemia-reperfusion injury, so chemiexcitation may underlie skin cancers arising in burn scars and it may operate during wound healing, hypertrophic scarring, skin flap reconstructive surgery, and skin aging. The same reactants are also present in neurodegenerations such as Parkinson’s Disease and Alzheimer’s, in deafness induced by noise or drugs, and in macular degeneration.

A first outcome of the 3.5 day conference will be a white paper outlining plausible chemiexcitation pathways for the diseases or pathologic reactions as well as identifying promising avenues of scientific investigation and feasible routes to blocking chemiexcitation.

A second outcome will be a website to provide a technical foundation for new colleagues – including young scientists. Modified versions of slides from the conference will be posted, including a recollection of what is already understood in each area, and presented as a list of principles and expositions in the style of Molecular Biology of the Gene. The website will also present lists of resources and the chemistry, biology, and pathology questions that are still in need of an answer.

Beneficiaries: Dr Simon G. Danby, Independent Research Fellow, University of Sheffield Medical School, UK, Professor Michael J. Cork and Mr J. Chittock, University of Sheffield, UK, and Dame, Professor Tina Lavender and Dr Alison Cooke, The University of Manchester, UK

Grant: DKK 2,115,500

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.

Beneficiary: Dr Emma Guttmann, Icahn School of Medicine at Mount Sinai, New York, NY, USA

Grant: DKK 11,500,000

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?

Beneficiaries: 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

Grant: DKK 708.500

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.

Beneficiaries: 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

Grant: DKK 2,558,500

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.

Beneficiaries: Anders Johannes Hansen, PhD, Associate Professor, University of Copenhagen, Denmark, Robert Gniadecki, MD, Professor, Dermatology Department, Bispebjerg Hospital, Copenhagen, Kim Holmstrøm, R&D Manager, Department of Biomedical Technology, Bioneer A/S, Denmark, and Nicola Segata, PhD, Assistant Professor and Principal Investigator, Computational Metagenomics, CIBIO, University of Trento, Italy

Grant: DKK 5,035,000

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.