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.

Investigating the tumor suppressive functions of Notch signaling during skin cancer initiation and progression

Grantee: Sunny Y. Wong, Assistant Professor, University of Michigan, Ann Arbor

Amount: DKK 2,486,354

Grant category: Research Grants in open competition

Year: 2018

Geography: USA

Basal cell carcinoma (BCC) is the world’s most common cancer and is defined by uncontrolled activation of the Hedgehog (Hh) signaling pathway.

Although previous studies have suggested that elevated Hh may be sufficient for BCC formation, mutations in the Notch pathway are also commonly observed. Furthermore, Notch-deficient mice are susceptible to forming BCCs, and our recent studies have shown that Notch can modulate tumor-drug response.

These studies seek to understand whether Notch affects multiple aspects of BCC tumorigenesis. Using a combination of animal studies and human BCC specimens, we will investigate how Notch modulates tumor progression and stem cell origin.

We will also model in mice a recent clinical trial, where Alzheimer’s patients treated with a Notch inhibitor reported increased incidence of BCC. We hypothesize that Notch may suppress tumorigenesis at multiple levels by controlling cell differentiation, apoptosis and turnover, similar to its function in normal skin and hair follicles.

These studies will ultimately build on the novel premise that BCCs may originate from a precursor lesion. Given that Notch mutations are the most commonly observed genetic aberrations in human skin, a deeper understanding of the tumor suppressive properties of this pathway is urgently needed.

Characterizing the disease memory in atopic dermatitis

Grantee: Patrick M. Brunner, Medical University of Vienna

Amount: DKK 2,920,541

Grant category: Research Grants in open competition

Year: 2018

Geography: Austria

Atopic dermatitis (AD), the most common chronic inflammatory skin disease, typically starts very early in life.

While many patients outgrow their disease, some develop chronic disease for the rest of their lives. Mechanisms responsible, however, are completely unknown, and no biomarker exists that can predict the course of the disease.

Thus, we want to compare skin from young adults that have outgrown their AD, with skin from patients with active disease (namely normal appearing AD under topical glucocorticoid treatment, which can be expected to flare up again after cessation of treatment, thus harbouring a “disease memory”).

Skin from healthy control subjects will serve as baseline comparators. Due to low immune cell numbers in this type of tissue, we want to use in vivo suction blistering of AD patients to obtain (i) skin resident immune cells and (ii) skin proteins. Suction blister fluid will be analysed with low cytometry and single cell RNAseq (for cells) as well as a proteomic multiplex assays (OLINK) for soluble proteins. The blister roof (i.e. the epidermis) will also be harvested, and keratinocytes will be stored in liquid nitrogen for functional experiments.

Results obtained from flow cytometry, single cell RNAseq and proteomic approaches will then be used for such functional in vitro experiments (e.g. co-culturing, skin equivalents, stimulation experiments) in future research projects.

Overall, we hope that the identification of cellular and/or molecular factors influencing the natural course of AD could possibly identify targets for novel therapeutic approaches in AD, that could induce long term remission – or even lead to a cure – of AD.

Compartmentalized and Systemic Interactions of the Skin Microbiome in Cancer Immunotherapy Response

Grantee: Julia Oh, Jackson Laboratory, Farmington, Connecticut

Amount: DKK 2,107,529

Grant category: Research Grants in open competition

Year: 2018

Geography: USA

My vision is to use metagenomics to better predict patient responses to immunotherapy and rationally design microbial adjuvant cocktails and engineered microbes to improve therapeutic outcomes.

However, a central question is the role of the local microbiota vs. systemic effects in potentiating these immunotherapeutics. In skin cancer, we have been studying how the skin microbiome affects predisposition and progression. Specific gut microbes have been implicated in the outcomes for immunotherapy response in melanoma skin cancer, supporting a role of systemic immune interactions via the gut in potentiating immunotherapy response.

However, because many aspects of cutaneous immunity are compartmentalized from systemic immune effects, we hypothesize that the skin microbiome could uniquely impact skin cancer outcomes during immunotherapy by modulating the cutaneous immune milieu.

The LEO Foundation Award 2017 – Silver Award

Grantee: Dr. Christoph Schlapbach

Amount: DKK 500,000

Grant category: LEO Foundation Awards

Year: 2017

Geography: Switzerland

The Silver Award went to Dr. Christoph Schlapbach, dermatology resident at the University of Bern in Switzerland.

“It is a great honour for me to receive the LEO Foundation 2017 Silver Award on behalf of my emerging research team. Together with the generous financial support, this prize motivates and supports our journey towards a better understanding of how the human skin functions,” said Christoph Schlapbach.

The LEO Foundation Award 2017 – Gold Award

Grantee: Dr. Maria Kasper

Amount: DKK 1,000,000

Grant category: LEO Foundation Awards

Year: 2017

Geography: Sweden

The Gold Award went to Dr. Maria Kasper, presently leading a research group at the Karolinska Institute in Stockholm, Sweden.

“Receiving the phone call with the news of the LEO Foundation 2017 Gold award is one of these few unforgettable moments. My friends often call me “skin nerd” since I love everything about skin.  Thus, it’s such a happiness and great honour for me to receive this prestigious prize. I would like to express my deepest thank you to the LEO Foundation, the ESDR, and my lab members who make everyday’s work fun and colorful,” said Maria Kasper.

GLP-1R signaling in T cells in relation to psoriasis

Grantee: Carsten Geisler, Professor and Head of Department, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen

Amount: DKK 2,000,000

Grant category: Research Grants in open competition

Year: 2017

Geography: Denmark

Recent studies of patients with psoriasis and type 2-diabetes have shown intriguing results: administration of glucagon-like peptide 1 (GLP-1) analogues was found to improve the severity of psoriasis. In another study, while not finding a significant beneficial effect of a GLP-1 analogue on disease score as compared to placebo, patients did report a significant decrease in their disease score as compared to baseline.

This has led a Denmark-based group to team up for further investigation of the effect of GLP-1 analogues on psoriasis, based on, among others, an assumption of a direct effect of GLP-1 analogues on the immune system – with the intention of clarifying if there may be a route to new treatment options for psoriatic patients.

More specifically, the team will investigate if the potential immunoregulatory effect of GLP-1R signalling on T cells in psoriatic plaques could be responsible for the patient-experienced alleviation of psoriasis. The team furthermore hypothesizes that vitamin D may play an important role in GLP-1R signaling and is important for alleviation of psoriasis as Vitamin D upregulates GLP-1R on T cells and low serum levels of vitamin D have been reported in psoriatic patients.

The majority of the experiments will be performed by Anna Kathrine Obelitz Rode under supervision of Martin Kongsbak-Wismann and Carsten Geisler, Department of Immunology and Microbiology, University of Copenhagen. Lone Skov, Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen will be co-supervisor on the project. The project will be performed in close collaboration with Charlotte Menné Bonefeld, Department of Immunology and Microbiology, University of Copenhagen.

The clinical studies in humans will be performed at the Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen in collaboration with Lone Skov.

Towards a personalized medicine approach for atopic dermatitis

Grantee: Dr Emma Guttmann, Icahn School of Medicine at Mount Sinai, New York

Amount: DKK 4,700,000

Grant category: Research Grants in open competition

Year: 2017

Geography: USA

Atopic dermatitis (AD) is the most common inflammatory skin disease, with a prevalence in adults of 3% to 10% and a large unmet need for effective therapeutics.

Current clinical trials for AD patients assume a common disease mechanism. However, based on preliminary data, different therapeutics may be required to effectively treat different subsets of AD patients.

Biomarker-based studies show distinct clinical, and particularly molecular and cellular differences between different AD subpopulations such as African American, Chinese, and Indian AD patient populations.

However the characterization of the different and distinct clinical AD phenotypes is still at its very beginning. Indeed, there is high need of appropriate mechanistic studies to create a complete “molecular map” of AD across its different variants and hence to get a step closer for a personalized treatment approach.

Dr. Emma Guttman and her team at Icahn School of Medicine at the Mount Sinai Medical Centre, NY, USA, will seek a first time investigation to provide a systems biology approach for AD aiming to produce a molecular map of AD across its different subtypes.

The project integrates cellular and molecular biomarkers of lesional, but also non-lesional, skin and systemic inflammation to classify adult AD patients based on ethnic phenotypes, disease severity and age differences.

The proposal will set the stage for personalized therapy approach for AD based on skin and blood biomarkers and pathogenic variation of AD phenotypes related to severity, race/ethnicity and age.

Epidermal and Dermal Stem Cells in Psoriasis

Grantee: Markus Frank, MD, Associate Professor, Harvard Medical School, Boston Children’s Hospital, Boston, Massachusetts; Christine G. Lian, MD, Assistant Professor, and George F. Murphy, MD, Professor, both Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts

Amount: DKK 3,000,000

Grant category: Research Grants in open competition

Year: 2017

Geography: USA

Despite decades of research, the root cause of psoriasis remains unknown and targeted approaches to cure psoriasis have to date been elusive.

Psoriasis is a physically and psychologically devastating skin disorder affecting more than 7.5 million Americans, with global prevalence ranging up to 4.6%. The disease causes profound physical, emotional, and social burdens translating into massive healthcare costs.

Theories of the biological mechanisms behind the disease range from genetic and epigenetic deviations to acquired defects involving a plethora of cellular and mechanistic culprits, including epidermal cell kinetics, endothelial-leukocyte interactions and perturbations in dermal nerve fibres, mast cells, lymphocytes and dendritic cells.

However, even if it is clear that a multiplicity of cellular pathways is involved, the primary events that initiate and drive disease remain unknown.

The team behind this study proposes a novel hypothesis that psoriasis is driven by immune-mediated dysregulation of stem cells within the epidermal and dermal compartments.

In the course of the study, the team will, for the first time, test the skin stem cell hypothesis of psoriasis causation with a highly-focused goal of defining the primary event(s) in lesion formation, thus providing a foundation for future pre-clinical targeted therapeutic approaches designed to actually cure psoriasis.

The pro-autophagic tumor suppressor AMBRA1 as a novel therapeutic target for melanoma

Grantee: Professor Francesco Cecconi, Head of the Cell Stress and Survival Unit (CSS), Danish Cancer Society Research Center (DCRC), Copenhagen

Amount: DKK 3,820,000

Grant category: Research Grants in open competition

Year: 2017

Geography: Denmark

The LEO Foundation has supported this project in appreciation of the fact that malignant melanoma has the highest death toll among skin cancer.

If and when melanoma is not diagnosed and treated early, the cancer may develop and spread to other parts of the body, where it becomes harder to treat and potentially fatal. Therefore, work to find new therapeutic targets for this particular aggressive cancer type is of extreme importance.

Professor Cecconi and his team have extensive and comprehensive expertise on the molecular ‘switch’ AMBRA1, believed to play a significant role in the body’s own defense against diseases such as cancer.

As an example, professor Cecconi was the first to identify the AMBRA1 gene and has been unraveling its multiple functions over the last 10 years. In particular, he has already demonstrated AMBRA1 playing a role as tumor suppressor in vivo, and preliminary data indicates the gene’s supposed role as a therapeutic target in cancer. Very intriguingly, most AMBRA1 mutations were found in melanoma patients.

The LEO Foundation finds this project to be innovative and commends its multidisciplinary approach, putting together different fields of research ranging from cell biology, mouse genetics, biophysics, computational biology and CRISPR/Cas9 technology.

Prof. Cecconi is member of the European Consortium Mel-Plex (Horizon 2020 Marie Curie Action), which includes several international researchers with the common aim of tackling melanoma – and these existing collaborations with melanoma experts will be of great importance in order to accomplish the project.