Explore our grantees and awardees

Grant category: Research Grants in open competition

Year: 2023

Geography: Norway

Ludvig Sollid’s project aims to improve the understanding of the pathogenic immune responses in dermatitis herpetiformis and hereby design and investigate potential new therapeutics for the disease.

Dermatitis Herpetiformis (DH) is a chronic autoimmune bullous skin disease characterised by itchy blisters localised at specific surfaces of the body. DH can be considered a cutaneous manifestation of the gluten sensitive condition Coeliac Disease (CeD). The treatment for DH, as it is for CeD, is a life-long gluten-free diet and therefore novel treatments are sought for.

The diagnosis of DH is made by detection of granular IgA deposits in the dermis layer of the skin. These IgA deposits are immune complexes involving the autoantigen transglutaminase 3 (TG3) which is expressed in the epidermis, the outmost layer that sits above the dermis.

In this project Ludvig Sollid and his team aim to dissect the immunopathogenesis of DH, specifically addressing the mechanism for the generation of TG3 autoantibodies. Based on a model for the generation of autoantibodies to another transglutaminase (transglutaminase 2, TG2) in CeD, they will explore whether B cells carrying B-cell receptors isolated from DH patients, can bind complexes of TG3 and gluten peptides and thereby present gluten peptides to T cells so that T-cell help is provided.

Specifically, they will characterise the substrate binding site of TG3, identify the preferred gluten peptide substrates for TG3, and also characterise, in detail, the structural basis for binding of DH autoantibodies including antibodies that augment TG3 activity.

Based on these new insights, the team will design TG3 inhibitors which have potential therapeutic usage for treatment of DH along with a TG2 inhibitor which recently proved efficacious for treatment of CeD.

Grant category: Research Grants in open competition

Year: 2023

Geography: Netherlands

Arjan van Laarhoven’s project aims to improve the treatment of patients infected with mycobacteria by looking at the patient’s individual immune responses to the infection and combining this with optimized treatment with antibiotics.

Non-tuberculous mycobacteria (NTM) can cause debilitating skin and soft tissue infections (SSTI). NTM SSTI incidence rises with an aged population and increased use of immunosuppression. These infections require treatment with multiple antibiotics for minimally 4-6 months. Still, non-response or worsening of skin lesions occurs frequently, because antibiotics fail or too much inflammation occurs.

Arjan van Laarhoven and his team hypothesize that differences in the patients’ immune systems, so-called ‘patient endotypes’, drive these diverging treatment courses. Currently, the involved immune processes in the skin are not identified for NTM SSTI. In addition, it is unknown what antibiotic concentrations in the skin are needed to kill the NTM.

In this study, the team will investigate the individual immune response in the skin of NTM SSTI patients by measuring the activity of genes in individual cells, and how these cells interact. They will compare this to the immune cells in the patients’ blood and will use the combined information to understand how patients differ in their immune response to the infection. These findings will be related to the clinical response to antibiotic treatment.

After eight weeks of antibiotic treatment, a second biopsy will be taken, in which measurement of the number of live mycobacteria and the local skin drug concentrations of azithromycin and clofazimine will be repeated.

By providing targets for optimizing treatment with both antibiotics and anti-inflammatory or immunostimulating drugs, this project aims to improve the outlook for NTM SSTI patients.

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.

Grant category: Research Grants in open competition

Year: 2023

Geography: USA

Ralf Paus’ project aims to elucidate the role of the fragrance linalool in the development of frontal fibrosing alopecia (a type of involuntary hair loss).

Frontal fibrosing alopecia (FFA) is an ever more common, disfiguring inflammatory hair disease of primarily post-menopausal women. Since many FFA patients are allergic to fragrances like linalool, contained in 63-90% of personal care/household products, Ralf Paus and his team investigated whether this lead fragrance can promote core FFA pathogenesis events in human scalp hair follicles (HFs), which express “smell” (olfactory) receptors (ORs) for this fragrance, and indeed linalool induced overexpression of a key inflammatory “danger/distress” signal (MICA), reduced the pool of HF stem cells, and transformed some of them into fibroblasts (EMT).

Thus, Ralf Paus and his team hypothesize that linalool causes overexpression of MICA and excessive chemokine secretion by stimulating specific ORs; this attracts MICA-responsive immune cells that induce bulge immune privilege (an anatomical area relatively protected from inflammatory immune responses) collapse and stem cell death or EMT, leading to hair loss and scarring.

In Aim 1, they will probe this hypothesis in organ-cultured healthy human HFs, and non-lesional scalp skin of linalool-sensitized FFA patients. In Aim 2, they will dissect mechanistically by OR1A1 or OR1C1 silencing (i.e., preventing certain ORs from being expressed) which linalool-induced, FFA-promoting events depend on OR signaling.

If they can confirm that linalool can promote or even initiate core FFA pathogenesis events, namely in sensitized individuals, this will identify a novel immunological stem cell damage mechanism and could have major consumer protection and preventive medicine implications.

Grant category: Research Grants in open competition

Year: 2023

Geography: USA

Patrick Brunner’s project aims to better understand the role of eosinophils, a type of granulocyte, in inflammatory skin diseases.

Granulocytes are key components of the innate immune system, that can react rapidly to various infectious agents and noxious stimuli. Despite their central role in host defense, their mechanistic relevance to human skin disease is still only insufficiently understood. Particularly eosinophils are prominently found in various inflammatory skin conditions associated with type 2 immune skewing (i.e., a response governed by T helper cells type 2 and a characteristic set of released cytokines, like IL-4 and IL-13). These include atopic dermatitis, bullous pemphigoid, hypereosinophilic syndrome (HES), urticaria, allergic reactions including DRESS (Drug reaction with eosinophilia and systemic symptoms), or parasitic infestations.

IL-5 is believed to be a key growth and differentiation factor for eosinophils. While IL-5 blockade is effective in e.g., HES, urticaria and DRESS, it is largely ineffective in atopic dermatitis or bullous pemphigoid, suggesting substantial functional eosinophil heterogeneity across these conditions. However, underlying mechanisms remain entirely unexplored, due to the difficulty in isolating and propagating these cells.

By using novel high-throughput analysis techniques such as single-cell RNA sequencing (scRNAseq) and spatial transcriptomics, complemented by functional in vitro experiments, Patrick Brunner and his team want to characterize eosinophils from skin and blood of patients with classic type 2 diseases, and define their in-situ skin tissue niche (i.e., microenvironment).

With this study, they hope to better understand eosinophil heterogeneity across skin diseases, define yet unrecognized subtypes within the human immune system, and help to develop better future treatment approaches.

Grant category: Research Grants in open competition

Year: 2023

Geography: USA

Shadmehr (Shawn) Demehri’s project aims to elucidate the potentially beneficial role of polyomavirus infections in lupus.

Lupus is a major autoimmune disease characterized by the immune system’s attack on the body’s tissues and organs. Lupus affects over 5 million individuals worldwide, with an estimated 16,000 new cases diagnosed annually in the United States alone. Chronic inflammation caused by lupus impacts the skin, kidneys, and brain. Despite significant progress in understanding the pathophysiology of autoimmune diseases, lupus patients continue to experience substantial morbidity affecting their quality of life.

Polyomaviruses are small DNA viruses that are commonly found in nature. In immunocompetent individuals, polyomaviruses persist at low levels in the host after the primary infection, usually without causing any noticeable symptoms. Clinical research suggests that lupus patients with polyomavirus DNA in their urine may exhibit reduced kidney inflammation and lupus antibodies.

These clinical observations, together with preliminary findings by Shawn Demehri and his team, suggest a potential protective role for commensal (i.e., naturally occurring and non-pathogenic) polyomaviruses in lupus. To investigate the role of polyomavirus as a novel lupus therapy, the group aims to: (a) elucidate the mechanisms by which polyomavirus suppresses inflammation, (b) examine the impact of polyomavirus on lupus development, and (c) determine the potential of polyomavirus to enhance the therapeutic effects of current lupus treatments.

By exploring these avenues, they hope to uncover new insights into the potential use of polyomavirus as a therapeutic strategy for lupus.

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.

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.

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.

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.