Explore our grantees and awardees

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.

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.

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.

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?

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.

Grant category: Research Grants in open competition

Year: 2016

Geography: Brazil, USA

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.

Grant category: Research Grants in open competition

Year: 2016

Geography: Austria

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.

Grant category: Research Grants in open competition

Year: 2016

Geography: Denmark, USA

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.

Grant category: Research Grants in open competition

Year: 2016

Geography: Denmark, USA

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.

Grant category: Research Grants in open competition

Year: 2016

Geography: Japan

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.