The LEO Foundation Award 2019 – Region Asia Pacific

Grantee: Dr. Tetsuro Kobayashi

Amount: USD 100,000

Dr. Tetsuro Kobayashi is a Research Scientist at the Laboratory for Innate Immune Systems, RIKEN, Center for Integrative Medical Sciences (IMS), Yokohama, Japan.

Dr. Tetsuro Kobayashi receives the award for his research in understanding the interaction between microbes and the immune system in skin.

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The LEO Foundation Award 2019 – Region EMEA

Grantee: Dr. Shoba Amarnath

Amount: USD 100,000

Shoba Amarnath is a Research Fellow at the Institute of Cellular Medicine at Newcastle University, UK

She receives 100,000 USD for her research in the field of immune tolerance in cutaneous inflammation.

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The LEO Foundation Award 2019 – Region Americas

Grantee: Maksim Plikus

Amount: USD 100,000

Maksim Plikus is Associate Professor at the Department of Developmental and Cell Biology, School of Biological Sciences, University of California, Irvine, USA

He receives 100,000 USD for his research in skin stem cells and regeneration.

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Unge Forskere (Young Scientists) 2019-2021

Grantee: Mikkel Bohm, ASTRA, Sorø, Denmark

Amount: DKK 6,000,000

Science is a powerful tool to understand and change the world for the better. The national Centre for Learning in Science, Technology and Health in Denmark – Astra* – wants to strengthen and develop science learning to train a new generation of young people with strong science competencies. It is important for the future of Denmark and our role in a globalized world.

One of Astra*’s activities is Unge Forskere (Young Scientists) which is Denmark’s largest talent competition for children from Danish elementary schools and high schools within STEM (Science, Technology, Engineering, and Mathematics).

The Unge Forskere-competition contributes to both talent development through participation in the competition, and it strengthens the work with innovation, idea development and the natural science method in daily teaching. It is a program that focuses both on the most talented young people, and generally strengthens the natural science identity and general science education among children and young people in Denmark.

Unveiling AMBRA1 as a prognostic biomarker in in vivo pre-clinical models of cutaneous melanoma

Grantee: Daniela De Zio, Danish Cancer Society Research Center, Copenhagen, Denmark

Amount: DKK 2,900,000

The survival rate of patients with advanced melanoma has improved in recent years due to the clinical application of immune checkpoint inhibitors, as well as kinase inhibitors in BRAF/RAS-mutated melanoma cases.

However, melanoma remains a fatal diagnosis as a consequence of emerging resistance mechanisms and the absence of reliable biomarkers that identify high-risk tumour subsets, therefore impacting the stratification of these subsets for novel adjuvant therapies.

In the search for novel oncosuppressors that are altered in melanoma, we have found a promising candidate in the protein called AMBRA1. AMBRA1 has a fundamental role in the positive regulation of autophagy – a process which can elicit both pro- and anti-tumorigenic roles. Additionally, AMBRA1 finely modulates other crucial oncogenic processes, such as cell proliferation, cell invasion, and cell death.

Our preliminary research in a mouse model of melanoma has proven Ambra1 to be a crucial oncosuppressor, whose expression has been found highly altered in a number of human melanoma cells. Thus, by applying melanoma cell and mouse models in combination with systems biology approaches and state-of-the-art technologies, we aim to decipher the response of Ambra1-deficient melanomas to the current therapies.

Moreover, we will investigate the role of Ambra1 in regulating lipid metabolism in melanoma, which has recently been shown to profoundly affect its progression. Additionally, our aim is to assess the prognostic relevance of AMBRA1 in human cohorts of melanoma patients and understand whether AMBRA1 expression correlates with disease progression and whether it influences treatment.

Outcomes from this project will pave the way for novel clinical insight into the prognosis and treatment of melanoma patients.

This project is co-supported by a Young Investigator award from the Melanoma Research Alliance (MRA) in the USA of 224,500 USD (https://www.curemelanoma.org/research/grants/).

Heritability of dermoscopic patterns in melanocytic naevi; a twin study

Grantee: Emmanouil Chousakos, National and Kapodistrian University of Athens, Greece

Amount: DKK 40,400

It is of the utmost importance for diagnosing melanoma on an early stage to identify high risk population groups, which will subsequently receive special screening and follow-up for their melanocytic lesions.

Managing patients with multiple naevi, including atypical mole syndrome patients, can be challenging for the clinicians, despite the introduction of dermoscopy, digital dermoscopy mapping and full body imaging in the everyday clinical practice.

The goal of this study is to prove the heritability of the dermoscopic pattern of melanocytic naevi. Evidence of a strong relation between the genome and the dermoscopic, hence histopathological image can be the fundament of a comparative approach among members of the same family in terms of evaluating their melanocytic lesions and their malignant potential. With this approach we will be able to establish a familial profile of the lesions.

Thermal Imaging in dermatology – Creation of the first database for artificial intelligence-based diagnostics

Grantee: Professor Alexander Navarini, Department of Dermatology and Allergy, University Hospital Basel

Amount: DKK 1,180,760

Thermal imaging is an investigational tool whose advantages are undisputed in engineering, i.e. for the non-destructive testing of composite materials, or in the photovoltaic industry.

The technique consists in measuring and imaging the thermal radiation and to convert this information into temperature maps, or thermograms. Medical applications of thermal imaging exhibit great potential and the field is currently experiencing a renaissance. One reason is probably the recent dramatic improvements of infrared cameras that are now affordable and compact and can even be connected to smartphones.

This project aims to produce a full body thermal imaging scanner for patients to later use as a next generation diagnostic tool, coupled with a 360° 2- and 3-dimensional digital photography device.

Our goal is to create the first open access skin thermograms database, large enough to enable artificial intelligence analysis. Such a tool could be very useful for the quantification and potentially prediction of affected areas in different skin disease such as psoriasis and eczema.

Novel quorum sensing inhibitors for anti-virulence treatment of skin infections caused by pathogenic Gram-positive bacteria

Grantee: Professor Christian Adam Olsen, Department of Drug Design and Pharmacology, University of Copenhagen

Amount: DKK 2,110,500

Staphylococcal bacteria are the most common cause of skin and soft tissue infections (SSTI) and with the rise of methicillin-resistant Staphylococcus aureus (MRSA) minor infections can lead to severe medical conditions.

The increasing antibiotic resistance development demands the search for alternative medicines with differing profiles ranging from prophylactic treatment of small infections to combating life-threatening conditions.

In the present project, we aim to inhibit this quorum sensing through a novel concept and thereby develop pan-staphylococcal inhibitors that are capable of treating the virulence in skin infections without the use of antibiotics.

Targeting the virulence of a bacterial infection rather than the viability of the pathogen represents such an alternative, because it increases the chance of clearance through the human immune system and attenuates disease symptoms while minimizing the risk of emerging resistance.

The expression of virulence factors in Gram-positive bacteria, including staphylococci, is regulated through quorum sensing (QS), which is a mechanism that allows bacteria to change gene expression in response to cell density.

This cell-to-cell communication is mediated by the secretion and detection of molecules termed autoinducing peptides (AIPs).

Functional characterization of dermokine in epidermal differentiation

Grantee: Professor MSO Ulrich auf dem Keller, Department of Biotechnology and Biomedicine, Technical University of Denmark

Amount: DKK 2,603,579

Epidermal renewal and keratinocyte differentiation are pivotal for skin homeostasis and maintenance of the skin’s barrier function, which is impaired in inflammatory skin diseases.

Expression of dermokine, a member of the stratified epithelium secreted peptides complex, is highly upregulated under these conditions, but its functional contribution to epidermal stratification and differentiation remains largely elusive.

We have identified dermokine as a substrate of the wound- and tumor-related matrix metalloproteinase (MMP) 10 in vitro and in vivo, a proteolytic processing event that might play a role in maintaining the phenotype of transient amplifying keratinocytes in hyperproliferative epidermis.

In this project, we will characterize the activity of dermokine and analyze its putative function in keratinocyte differentiation. Using advanced proteomics, we will identify surface binding proteins for dermokine on keratinocytes. Newly identified dermokine-receptor interactions will be characterized and related to signaling pathways that are activated in response to dermokine binding.

To test the hypothesis that MMP10 modulates dermokine activity, we will analyze the full-length protein in comparison to a truncated mutant, resulting from MMP10 cleavage. This mutant will be characterized for altered effects on keratinocyte differentiation, binding to receptor candidates and activation of downstream signaling.

This study will provide insight into the function and mechanisms of action of dermokine in normal and hyperproliferative epithelia and add to current knowledge on MMPs as modulators of extracellular signaling ligands in the skin. Anticipated results will help to devise new strategies for therapeutic intervention with barrier defects in inflammatory skin diseases.

Exploiting the untapped potential of the dermis to provide novel insight into the function of the skin microbiome

Grantee: Assistant Professor Christopher James Barnes, PhD, Natural History Museum of Denmark, University of Copenhagen

Amount: DKK 2,388,289

The skin microbiome has been thought to be highly individual, a kind of ‘microbial fingerprint’.

Yet scratching beneath the surface with DNA metabarcoding different skin compartments, we have found considerably less variation in the bacterial communities of the dermal compartment compared to the outer epidermal, challenging this dogma.

Here, we will extend upon these findings by performing a more comprehensive shotgun metagenomic approach, assessing whether compositional differences in the dermal and epidermal microbiomes effect their functioning.

The invasiveness of biopsies has been a major limitation in sampling of dermal microbiomes. Tape-stripping is a minimally invasive technique that penetrates through the epidermal compartment to the barrier with the dermis, and here we assess whether tape-stripping can substitute biopsies in accessing the potentially more informative, less environmentally variable skin microbiomes.

Finally, we will compare the dermal microbiomes of healthy controls to patients suffering atopic dermatitis (AD). Sufferers of AD have been repeatedly shown to have a perturbed epidermal microbiome, but they also have perturbed immune systems. Here we perform shotgun metagenomic and metatranscriptomic approaches to test for functional differences between the microbiomes of AD patients and healthy controls.

Studying the differences between healthy and diseased dermal microbiomes may ultimately fast-track identifying influential microbes associated with diseases, and their function within them.