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Grant category: Research Grants in open competition

Year: 2016

Geography: Ireland, United Kingdom, USA

This is an exciting project that, with the international group’s extensive research and know-how in mind, has the potential to create an intriguing base for novel personalised treatments for atopic dermatitis (AD). The project moreover holds an innovation potential that may make it stand out in the emerging global bio-economy.

The prevalence of AD, an inflammatory skin disease resulting in itchy, red, swollen and cracked skin, is constantly increasing. Today, it affects 15-30 percent children and 2-10 percent adults worldwide, presenting a significant economic burden to healthcare systems.

There is no cure for AD, only soothing of the symptoms. In the majority of AD patients, the disease is a consequence of a blend of genetic defects of the skin barrier defects and abnormal immune responses influenced by environmental factors.

Until now, the models used to assess the interplay are not particularly predictive. The group behind this project aims to change this by using the latest advances in stem cell science, gene editing and tissue engineering to develop and validate innovative 3D in vitro models of skin – making the models similar to skin in AD patients by emulating full thickness skin of varying barrier integrity; faulty, partially repaired or intact, and immune response composition.

As part of the project, the group will also develop mathematical computer models to accurately address the predictive, prognostic and therapeutic outcome of personalised AD therapy – in order to address co-dependence of the quantitative and qualitative changes in skin barrier and activation of immune cells.

The 3D models will also be made available to test various novel therapeutic approaches for AD treatment in a patient specific manner.

Grant category: Research Grants in open competition

Year: 2021

Geography: United Kingdom

Claire Higgins’ project aims to develop an early-stage diagnostic tool for scleroderma, a disease caused by an overproduction of collagen in both the skin and connective tissues, leading to a scarring of the skin and internal organs.

Among the early symptoms of scleroderma are poor blood circulation in fingers and toes, and an increased sensitivity to cold, which in many aspects is comparable to the much more common Raynaud’s phenomenon, and hence, scleroderma is often undiagnosed.

Utilizing the fact that certain molecules change expression level during disease (‘biomarker’ molecules), Claire Higgins aims to identify scleroderma-specific biomarkers in the liquid between individual skin cells, i.e., in the skin interstitial fluid. The identified biomarkers will be used to develop a non-invasive and painless test for general practitioners (GPs), enabling fast diagnosis – within minutes – and thereby differentiation between patients suffering from scleroderma and Raynaud’s phenomenon. Thus, patients will be able to get the most relevant intervention as early as possible. The actual diagnostic test will be developed along with the biomarker identification.

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: 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.

Grant category: Standalone grants

Year: 2019

Geography: Denmark

Researchers in immunology, cell biology and cancer were first movers in single-cell sequencing when they demonstrated a huge potential of this novel technology to unravel novel cell populations and disease heterogeneity.

This approach has gained further momentum fueled by new, exiting studies in neurobiology and rheumatology. So far, single-cell sequencing has not been used in relation to skin diseases – with few exceptions such as our new study on single-cell sequencing in cutaneous T cell lymphoma (CTCL) – the first paper of its kind – which was rapidly followed by three additional papers on single-cell sequencing in CTCL.

Moving from investigating an average of molecular changes in thousands or millions of cells to the study of changes in the transcriptome in single cells is critical to obtain a deeper and more precise understanding of disease heterogeneity and novel disease mechanisms. In other words, single-cell sequencing is expected to become the novel golden standard in all areas of research related to immunology and inflammation including the scientific focus area of the LEO Foundation Skin Immunology Research Center.

The “package” provides the sufficient capacity to conduct state-of-the-art single-cell analysis in the key areas of the LEO Foundation Skin Immunology Research Center. In order to get maximal advantage, value, and rapid implementation of the instruments, we will employ a novel protocol for this platform to run up to 5 different modalities (mRNA, TCRab, TCRgd, surface proteins, sample hashing and CRISPR lead sequences) in parallel to top-tune the technology.

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.