GWA studies on common dermatological diseases

Grantee: Professor Gregor B. Jemec, Department of Dermatology, Zealand University Hospital, Roskilde, and Assoc. Professor Ole B. V. Pedersen, Department of Clinical Immunology, Næstved Hospital

Amount: DKK 5,770,000

Grant category: Research grants in open competition

Year: 2018

Geography: Denmark

In this study, the group led by Professor Gregor Jemec of Roskilde Hospital has set out to identify new genes for the development of a long line of common dermatological conditions, including deep skin infections, warts, fungal infections, and eczema.

Many of these common skin diseases are still poorly understood and the treatments often insufficient. A study of the genetics of these disorders will help increase the understanding of the pathogenic mechanisms. The study will have its origin in Denmark and be based on unique national biobanks, national registries, and with extensive genetic analyses done in collaboration with deCODE Genetics, Iceland.

This is possible due to the growing number of Danish large-scale biobanks as well as biobank based scientific studies suited for further genetic studies. The largest genetic study in Denmark is the Danish Blood Donor Study (DBDS) in which the genome wide association (GWA) arrays have been analysed on 110,000 research participants.

In addition to this cohort, Jemec’s group is currently pursuing genetic testing on the Copenhagen Hospital Biobank (CHB) that includes samples from around 350,000 patients. Both of these biobanks have established a collaboration with deCODE Genetics, Iceland – one of the leading genetic research centers in the world.

 

Project Group

Henrik Ullum, Professor, Department of Clinical Immunology, Rigshospitalet

Søren Brunak, Professor, Center for Protein Research (CPR), Copenhagen University

Simon Francis Thomsen, Professor, Department of Dermatology, Bispebjerg Hospital

Claus Zachariae, Professor, Department of Dermatology, Gentofte Hospital

 

International affiliations

Ingileif Jonsdottir, Professor, deCODE Genetics, Iceland

Errol Prens, Professor, Department of Dermatology, Erasmus University, Rotterdam, Netherlands

Christos Zouboulis, Professor, Department of Dermatology, Brandenburg Medical School Theodor Fontane, Dessau, Germany

Development of biomarkers and models for wound infection

Grantee: Mariena van der Plas, University of Copenhagen, Faculty of Health and Medical Sciences, Department of Pharmacy

Amount: DKK 2,745,375

Grant category: Research grants in open competition

Year: 2018

Geography: Denmark

Proper wound healing is a fundamental survival mechanism and dysfunctions cause significant disease, such as seen in infections after burns, trauma and surgery, as well as in non-healing ulcers.

Currently, the prevalence of non-healing wounds is estimated to be over 40 million worldwide, a number projected to rise with 6-9% annually, due to aging of the population and the increasing incidence of diseases that contribute to nonhealing ulcer development, such as obesity and diabetes.

There is a great and unmet need for novel treatments for improved healing, and thus better predictors for wound healing outcomes are essential. Given the importance of innate immunity and microbial interactions for development of impaired wound healing, the aim of this project is to define novel prognostic and diagnostic biomarkers for assessment of wound healing and infection risk.

For this purpose, we will use state-of-the-art techniques for peptidomics mass spectrometry. This unique approach, without the classical trypsin digestion of the samples, will give actual insight in processes occurring in the wound bed, e.g. enzymatic activity, infection, inflammation, and angiogenesis, instead of just reporting the presence of a protein, independent of the state it is in.

Furthermore, we will set up biological models for validation of biomarkers, as well as novel treatments. Together, the outcomes of these studies have the potential to improve diagnostic evaluations of wounds, and will enable us to develop novel treatment concepts for early prevention of infection, leading to improved healing results for large and significant patient groups.

Neutron reflectivity of healthy and atopic dermatitis lesional skin lipid models

Grantee: Kathryn Browning, LEO Foundation Centre for Cutaneous Drug Delivery (LFCCDD), Department of Pharmacy, University of Copenhagen

Amount: DKK 2,234,415

Grant category: Research grants in open competition

Year: 2018

Geography: Denmark

Atopic dermatitis (AD) is a chronic disorder caused by the improper function of the skins barrier layer, the stratum corneum (SC). It is thought to affect between 15 and 30% of children and up to 10% of adults.

The need to develop drugs and drug delivery vehicles which effectively, and possibly specifically, interact with the compromised skin of AD patients is of great importance.

However, to date most pre-clinical trials utilise healthy skin, excised from surgical procedures, to investigate the penetration and interactions of drugs targeted to skin disease. This approach does not accurately represent lesional or diseased stratum corneum.

This project aims to develop models of the stratum corneum to compare the lipid multilayer structure and interactions of healthy and atopic dermatitis (AD) lesional stratum corneum. Key to the success of these models is access to a wide variety of skin lipids not commercially available and crucial to the realistic self-assembly of the lipid multilayers observed in SC.

An example of a currently unavailable lipid is the long chain esterified ceramides, Ceramide[EOS], which has been linked to the formation of long periodicity phases and lower permeability in SC and is often deficient in AD patients.2-4 These lipids will be obtained by extraction, separation and purification of ceramides from pig skin SC. Lipid mixtures of ratios found in healthy and AD lesional skin will then be self-assembled on a solid support and investigated for interactions with drugs and drug delivery vehicles using neutron reflection, which offers unique opportunities for angstrom level structural resolution and, through selective deuteration, the ability to highlight specific components of the system to improve contrast.

Local targeted immunotherapy for treatment of squamous cell carcinomas

Grantee: Merete Hædersdal, Bispebjerg Hospital

Amount: DKK 2,358,825

Grant category: Research grants in open competition

Year: 2018

Geography: Denmark

Squamous cell carcinoma (SCC) together with basal cell carcinoma comprises the absolute majority of non-melanoma skin cancers, affecting 150,000 persons in Denmark, equivalent to 3% of the population.

SCC’s cost is consequently substantial, reflected by notable patient morbidity, heavy socioeconomic burdens and significant mortality in immunosuppressed populations.

In oncology, systemic immunotherapies with PD1 and CTLA4 antibodies have had revolutionizing impact on clinical cancer treatment. Recognizing the immense potential of these strategies also for SCC, our vision is to pioneer a new local treatment approach by harnessing the immune system to combat SCC, while at the same time avoiding side effects associated with systemic treatment.

In a three-tiered translational project, we thus aim to deliver PD1 and CTLA4 antibodies through the skin using ablative fractional laser (AFL), effectively opening the door to implementation of topical SCC immunotherapy. The project is executed in collaboration with the Wellman Center at Harvard Medical School and Center for Cancer Immune Therapy at Herlev Hospital. The 3-year research plan comprises preclinical studies on biodistribution and pharmacokinetics in healthy skin, a proof-of-concept study in a well-established murine model for human SCC, and an explorative clinical study in SCC patients from the skin cancer clinic at Bispebjerg Hospital. For patients, topical immunotherapy may constitute a safe treatment with decreased morbidity and the prospect of potentially reduced risk of future SCC occurrence. This in turn will lower the socioeconomic burden of repeated treatments for a large cancer patient group, including high-risk immunosuppressed patients such as organ transplant recipients.

Investigating the role of human periostin in healthy skin and severe eczema

Grantee: Jan J. Enghild, Aarhus University

Amount: DKK 3,045,231

Grant category: Research grants in open competition

Year: 2018

Geography: Denmark

Severe eczema, also known as atopic dermatitis (AD) is the most common inflammatory skin disease resulting in itchy, inflamed, and swollen skin that is very susceptible to infection. It is estimated that 15-20% of all children and 2-10% of adults are affected, without effective treatment.

Because of this, significant public health burden and the lack of safe and effective treatments, there is a need for novel targeted therapeutics that can help manage symptoms and improve the quality of life for the patients.

The protein periostin is expressed in the skin and is implicated in AD. Significantly, studies have shown that the elimination of periostin in an AD mouse model reduces or completely removes the symptoms making periostin an apparent therapeutic target. However, the physiological functions of periostin remains unclear and a reduction or elimination of the protein in the skin could have severe side effects.

Therefore, a deeper understanding of the physiological role in healthy and diseased skin must be established. The interdisciplinary research team behind this project propose to address these issues and establish the function of periostin using in vitro and in vivo experimental setups including primary cell cultures, zebrafish, mouse models and human specimens combined with advanced biochemical methods. Novel therapeutics are urgently needed, and this project aim is to establish a strategy for the development of new treatment paradigms for AD, leading towards novel, innovative therapeutic strategies.

Skin Proteomic Atlas – a spatially and cell-type resolved landscape of protein expression in the human skin

Grantee: Matthias Mann and Beatrice Dyring-Andersen, University of Copenhagen

Amount: DKK 100,000

Grant category: Education and awareness grants

Year: 2018

Geography: Denmark

The skin is an amazing and complex organ that comprises multiple layers and cell types that are functionally distinct.

The aim of this study is to characterize the molecular composition of the healthy human skin by creating an atlas of all the proteins expressed in healthy skin as a function of their spatial location as well as its major cell types.

This atlas, comprising the identification of a global proteomic composition of human skin, will provide an important resource to the community studying the physiology and cell biology of the skin and serve as a basis for future studies comparing the proteomes of inflammatory and oncologic skin diseases.

Publication of the skin atlas will be accompanied by a freely accessible and well-advertised web page portal where information on proteins of interest and their protein profiles in the layers of the skin will be easily available.

LEO Foundation Skin Immunology Research Center

Grantee: University of Copenhagen

Amount: DKK 250,000,000

Grant category: Strategic grants

Year: 2018

Geography: Denmark

Diseases of the skin affect a quarter of the population, more than a billion people, at any given time. Despite impressive progress, especially in the area of immunology in skin diseases, the pace of innovation is not sufficiently high and new treatments are slow to reach patients.

Here, we propose to create a LEO Foundation Skin Immunology Research Center (Skin Immunology Center) that will become a beacon for skin research in Denmark and worldwide.

The Center will identify key questions relating to disease heterogeneity, new pathological mechanisms, and novel therapies of inflammatory skin diseases. With the ultimate aim of helping people with skin diseases in the best possible way, we will launch a focused effort employing cutting edge technologies to advance biological insights and translate basic discoveries to ‘proof of principle’ and then to ‘first in man’ applications (‘bench-to-bedside’). Importantly, observations and questions arising in the clinic will be taken back to the laboratory (‘bedside-tobench’). This team science concept and ecosystem with seamless translation and back-translation between basic biology and the clinic will animate the spirit of the Center from day one.

The Skin Immunology Center will be headquartered at the 12th floor of the Mærsk Tower, the new flagship building at the Faculty of Health and Medical Sciences, University of Copenhagen.

We will bring together the immunology of the skin, its diseases and comorbidities, ‘omics’ technologies, experimental models, and strong clinical integration to develop new stratification paradigms and therapies towards precision medicine. People will form the basis of the success of the Center and we will both empower existing scientists and strategically hire new talent. We will build a pipeline of future top researchers through excellent educational activities. In this way, the Center will incubate and form a new generation of multidisciplinary skin immunology researchers, ready to reshape the field for decades to come.

From the start, we will collaborate across specialties, institutions and geographies. The Skin Immunology Center will aim to have a total of 60 members in the core member research groups when fully operational, a critical mass allowing it to contribute significantly to raising the level and quality of research and education in inflammatory skin diseases.

The existing LEO Foundation Center for Cutaneous Drug Delivery will become an associated and collaborating partner. The Skin Immunology Center will integrate and advance basic and clinical science approaches to skin disease and develop future leaders in the field, while increasing knowledge and awareness of skin and skin diseases among medical professionals, patients and the public.

Bloom Festival 2019

Grantee: Svante Lindeburg, Golden Days

Amount: DKK 500,000

Grant category: Education and awareness grants

Year: 2018

Geography: Denmark

Bloom – at the core:

Bloom is an innovative festival about science and nature, which enlighten us on the Universe, the World and Ourselves. Framed in the lush Søndermarken at Frederiksberg in the heart of the capital city of Denmark, where some of the World’s greatest scientists, poets and philosophers have found inspiration through history, Bloom emerges each Spring as a sensual, experimental and thought-provoking festival version of natural sciences.

Prepared and communicated by some of the brightest scientists, thinkers, and artists of our time from here and abroad. By uniting the best from the world of festivals with the best from the scientific world, Bloom arm wrestles with Life’s greatest questions and over two days invite the audience to debates, talks, laboratories, conversations and nature walks under open skies.