Explore our grantees and awardees

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.

Grant category: Research Grants in open competition

Year: 2016

Geography: USA

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.

Grant category: Research Grants in open competition

Year: 2016

Geography: Denmark

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.

Grant category: Research Grants in open competition

Year: 2016

Geography: Denmark

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.

Grant category: Research Grants in open competition

Year: 2016

Geography: Denmark

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.

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.

Grant category: Research Grants in open competition

Year: 2016

Geography: USA

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.