High-resolution identification of bacterial-host interactions in atopic dermatitis during flare development and treatment

Grantee: Blaine Fritz, Postdoc, University of Copenhagen

Amount: DKK 2,956,179

Grant category: Research Grants in open competition

Year: 2023

Geography: Denmark

Blaine Fritz’s project investigates the ongoing genetic changes and interactions between bacteria and patients’ skin during development of atopic dermatitis to identify novel putative treatment targets.

Atopic dermatitis (AD) is one of the most common skin diseases, affecting up to 20% of children and 10% of adults. AD presents as localized, itching patches of eczema, frequently first observed during childhood and often persisting throughout the patient’s life.

Dysregulated immune response, microbial imbalances, and skin barrier dysfunction are among several, interacting factors, which invoke and perpetuate AD. In up to 90% of patients, aggressive pathogens such as Staphylococcus aureus displace the protective microbiota of the skin resulting in reduced microbial diversity and increased lesion severity. Clinicians commonly utilize antibiotics to treat bacterial infection in AD, but the efficacy is unclear and antibiotic treatment increases the probability of resistance.

The mechanisms and specific gene targets involved in host-microbial interactions by both commensal (non-pathogenic) and infecting bacteria are not well studied. This project hypothesizes that both protective and pathogenic bacteria on the skin dynamically activate specific host-genes and pathways during progression of an AD flare. To test this hypothesis, Blaine Fritz will utilize an integrated, machine-learning-based approach to identify longitudinal (i.e., over time) changes in gene-expression associated with the presence of specific bacteria during flare and treatment to identify direct, host-microbial interactions.

The findings will aid in elucidating bacteria’s role in AD and may guide antibiotic treatment, as well as identify novel targets for antibiotic-independent treatments.

Developing a vaccine, and characterizing the protective immunity, to prevent skin infection with Streptococcus Pyogenes

Grantee: Jes Dietrich, Senior Scientist, Statens Serum Institut

Amount: DKK 3,920,493

Grant category: Research Grants in open competition

Year: 2023

Geography: Denmark

Jes Dietrich’s project aims to develop a vaccine against a common pathogenic bacterium.

Streptococcus Pyogenes (Group A streptococcus, GAS) is a human pathogen causing billions of infections each year throughout the world. GAS is one of the most important bacterial causes of skin and soft tissue infections worldwide. There is no vaccine against GAS and the optimal immunity to protect the skin against GAS infection is still not fully known.

Jes Dietrich and his team have recently characterized the recognition of all GAS proteins in previously infected human adults and children, and successfully identified several GAS antigens that showed protective potential against a GAS skin infection.

Here, they will follow up on these discoveries. The aim is to produce a vaccine hybrid construct that will target several antigens on the bacterial surface as well as several of the bacterium’s early key immune inhibiting functions. Moreover, they will also investigate the immune correlates of skin protection.

Thus, the goal for this project is to develop a vaccine that protects against a GAS skin infection, and which is ready to proceed towards future clinical trials.

Research Stay at Brigham and Women’s Hospital, Boston, USA

Grantee: Beatrice Dyring-Andersen

Amount: DKK 1,157,196

Grant category: Research Networking

Year: 2023

Geography: Denmark

The main purpose of the research stay is to gain hands-on experience on two state-of-the-art technologies, namely spatial transcriptomics, which enables the investigation of gene expression across a tissue and CRISPR technology, which is an advanced method to edit genes within cells to investigate the function of specific genes in health and disease or to modulate cell functionality. These technical skills will be developed as part of two primary research projects to be conducted during the research stay.

Re:solve Global Health

Grantee: Mette Halborg Thorngaard

Amount: DKK 697,700

Grant category: Education and Awareness Grants

Year: 2023

Geography: Denmark

Re:solve is a not-for-profit global journalistic communication platform managed from Denmark sharing insights and solutions to how we can build more equitable health systems and healthier societies. The purpose of the project granted by Leo Foundation is to create awareness about the burden of skin disease and the burden and complexities of disease stigma through production and publication of two in-depth reports on these topics consisting of a number of articles and other communication pieces. The report on skin disease burden will be supplemented by a high-level roundtable discussion during World Health Assemby 2024, and the disease stigma report by a digital roundtable session and workshop.

Biotech Academy

Grantee: Kaare Skovmand Elnegaard

Amount: DKK 193,136

Grant category: Education and Awareness Grants

Year: 2023

Geography: Denmark

The project supports the 2023 Biotech Academy Camp which is a week-long science camp for 30 high school students in October. The camp combines theory and lab work, and this year’s program is focused on societal challenges. It is free of charge and also covers participants’ transportation to the camp, has been executed annually since 2008, and is run by master’s and bachelor students from the Technical University of Denmark and the University of Copenhagen.

Eksemskolen Kalaallit Nunaat

Grantee: Lone Storgaard Hove

Amount: DKK 970,540

Grant category: Education and Awareness Grants

Year: 2023

Geography: Denmark

The overall purpose of the pilot project is to increase awareness about atopic dermatitis in children in Greenland and facilitate treatment in remote areas by creating an Eczema School targeting health care staff with no expert knowledge on skin diseases, afflicted children, and their close relatives. There is a high prevalence of atopic dermatitis in Inuit children and the geographical conditions make diagnosis and efficient care difficult. The idea is to establish a school concept in four different areas, which is ready to be implemented, run, and financed locally in the future, in part by the initiative alleviating some of the current strain on the Greenlandic healthcare system.

Teach First Danmark

Grantee: Jesper Christensen

Amount: DKK 1,443,750

Grant category: Education and Awareness Grants

Year: 2023

Geography: Denmark

Teach First is a nonprofit recruitment program that enrolls academics in an employment-based training program to become certified schoolteachers, mainly within STEM fields and in schools in socio-economically disadvantaged areas. The purpose of the project is to double the reach of the program by preparing an expansion to western Denmark and to increase the financial sustainability of the program via economy of scale and increase of schools’ share of costs.

Outside-to-inside: understanding aberrant proteolysis in primary barrier defects as drivers of atopic dermatitis

Grantee: Ulrich auf dem Keller, Professor, Technical University of Denmark

Amount: DKK 2,865,186

Grant category: Research Grants in open competition

Year: 2023

Geography: Denmark

This project of Ulrich auf dem Keller aims to elucidate the potential role of a set of recently discovered proteins in atopic dermatitis that may contribute to disease development.

Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects people of all ages. It is one of the most common skin diseases, affecting approximately 10-20% of children and 1-3% of adults worldwide. AD can be a frustrating and uncomfortable condition that can significantly impact a person’s quality of life.

Despite extensive research it is not fully clear, if AD is primarily caused by a defect barrier function of the skin, allowing uncontrolled entry of environmental allergens that trigger an immune response, or by immunological disorders that in turn weaken the skin’s protective barrier, exaggerating the disease in a vicious cycle. Most likely, both contribute to predisposition and development of AD, but there are differences between patients which call for customized therapies.

Together with basic skin researchers in Switzerland and dermatologists in Germany, Ulrich auf dem Keller has identified proteins in non-lesional skin of AD patients whose activities might impair skin barrier integrity mostly independent of an immune response. This project will use human skin models and advanced protein analytics to understand if and how they might exert these detrimental activities and thereby contribute to predisposition to AD in affected individuals. Moreover, they will test their findings in samples from AD patients with a long-term aim to contribute to new strategies for development of therapeutics as alternatives to frequently applied emollients in barrier repair therapy.

Curing calcinosis: Dystrophic calcinosis in patients with Systemic Sclerosis undergoing treatment with Sodium Thiosulfate – Assessed by novel biomarkers and diagnostic imaging

Grantee: Mette Mogensen, Chief Consultant, Associate Professor, Bispebjerg and Frederiksberg Hospital

Amount: DKK 3,322,500

Grant category: Research Grants in open competition

Year: 2023

Geography: Denmark

This research project aims to synergistically improve patient treatment and improve understanding of the underlying biological and chemical mechanisms of cutaneous dystrophic calcinosis (DC) – a disease causing exaggerated deposition of calcium salts in skin.

These pathological calcifications cause severe ulcerations and pain in patients with systemic sclerosis (SSc) and negatively impact their quality of life. Today, reliable methods of quantifying the distribution, volume and composition of calcium crystal deposits are lacking.

Combining the expertise of data scientists and molecular biologists with medical experts in the field of radiology, dermatology, and rheumatology, Mette Mogensen and her team will create a new approach for quantifying calcium crystal deposits in skin and soft tissue in patients suffering from SSc, which is highly needed to monitor disease progression and potential treatment effects in future clinical trials. Several smaller studies have shown a potential for treating DC using sodium thiosulphate (STS). The aim of this study is to explore the characteristics of DC and investigate how STS treatment effects can be monitored over time with novel biomarkers (from blood and skin biopsies) and by advanced imaging technologies.

The vision is to cure calcinosis and the goal of this project is to increase quality of life for patients by development of an effective, targeted treatment that may offer therapeutic potential to all DC patients globally.

Unravel fibroblast-epithelial crosstalk supporting keratinocytes self-renewal to improve skin graft production

Grantee: Mariaceleste Aragona, Associate Professor, Novo Nordisk Foundation Centre for Stem Cell Medicine

Amount: DKK 3,999,975

Grant category: Research Grants in open competition

Year: 2023

Geography: Denmark

In this project Mariaceleste Aragona, in collaboration with Elena Enzo (University of Modena and Reggio Emilia, Italy), aims at the optimization of skin graft production for regenerative and replacement purpose.

Skin grafts for transplantation purposes are generated from epidermal stem cells. These regenerative therapies are life-saving procedures and have been demonstrated to be successful and safe for the treatment of burns and severe genetic diseases. Long lasting skin regeneration requires the correct amount of stem cells (SCs) in the graft. However, the treatment of large burns or skin replacement therapy in elderly patients are still challenging.

In such situations, the limited area of donor sites, and the physiological reduction of the number of SCs results in insufficient availability of SCs for graft production. A way to efficiently produce more SCs is to enforce their self-renewing – the process of generating more SCs – capacity.

A condition that forces SCs to increase their self-renewal capacity is tissue stretching. In this project, Mariaceleste Aragona aims to generate a comprehensive atlas of the changes occurring in space and time during tissue stretching. Based on this atlas, they will elucidate the signaling molecules instructing SC’s self-renewal and identify options to target such molecules. This knowledge will be used to develop cell culture conditions to ameliorate skin graft productions for clinical application.

Collectively, such insights will provide new fundamental knowledge on the biology of SCs and this approach may improve the clinical success of skin regenerative and replacement therapies to the benefit of patients.