Explore our grantees and awardees

Grant category: Research Grants in open competition

Year: 2022

Geography: Denmark

This project, led by Søren Degn, aims to investigate the role of a newly discovered immune cell, the T follicular regulatory cell (Tfr), in controlling systemic autoimmunity.

Søren Degn and his team have discovered that Tfrs are able to maintain tolerance in the skin even in the face of systemic inflammation, which in that case appear to be reversible, but also that if Tfr control in the skin fails, the systemic inflammation becomes irreversible and chronic.

Using a mouse model where Tfrs are selectively deleted, Søren and his team will investigate immune responses and identify which specific self-antigens are targeted when the tolerance maintained by the Tfrs is lost.

Grant category: Research Grants in open competition

Year: 2022

Geography: United Kingdom

This project, led by Francesca Capon, investigates the molecular and cellular mechanisms of dupilumab-associated conjunctivitis (inflammation of the eye), a comorbidity seen in one in three AD patients treated with the drug.

These mechanisms are poorly understood, and Francesca’s team wants to elucidate them by comparing immune profiles in blood samples from affected and non-affected patients. In addition, they will identify inflammatory molecules released by cultured immune cells treated with dupilumab to further understand the key signaling pathways.

The findings will enhance the understanding of dupilumab-induced conjunctivitis and eventually help improve treatment of patients with this condition.

Grant category: Research Grants in open competition

Year: 2022

Geography: USA

This project led by Dr. Nathan Archer investigates the interplay between bacterial colonization and a specific immune cell, the eosinophil, in development of atopic dermatitis (AD).

AD is a very common skin disease, particularly amongst young people, and the associated healthcare costs in the U.S. alone are estimated at USD 5.2 billion. Thus, there is a strong incentive to better understand the disease to improve its treatment.

The cause of AD is still unclear, but one interesting observation is that a specific type of immune cell, the eosinophil, infiltrates the affected areas and correlates with disease severity. The role of these eosinophils in AD remains unknown, but initial observations by Dr. Archer and his team point to a link between skin colonization of a specific bacteria, Staphylococcus aureus, and the observed infiltration – which may lead to both inflammation and itch. This bacteria-immune cell interaction is unusual, and Dr. Archer and his team will investigate the observed interaction in detail, with an aim to provide novel therapeutic targets for the treatment of AD.

Grant category: Research Grants in open competition

Year: 2022

Geography: Ireland

Chronic itch (pruritus) is a major symptom of numerous dermatological and systemic diseases, which substantially impairs patients’ quality of life, resulting in considerable socioeconomic costs. Current treatment options have insufficient efficacy or side effects, and do not treat the underlying cause of itch. Thus, there is a significant unmet medical need for a better efficacy, longer lasting and safer therapy.

Specifically, Jianghui and her team will focus on understanding the role of b-type natriuretic peptide (BNP) signaling, which is known to be pivotal in the development and transmission of itch, yet no effective therapeutics targeting this molecule have so far been developed. To address this knowledge gap, the team will investigate the pathways in detail, validate the involved molecules as potential targets for anti-itch drugs and develop therapeutic candidates that can interrupt several key molecular events of BNP signaling, including release of BNP and its pruritogenic effect.

Grant category: Research Grants in open competition

Year: 2022

Geography: USA

Amanda Nelson’s project investigates the role of two proteins, E-cadherin and p120, in the relatively common inflammatory skin disease Hidradenitis Suppurativa (HS), which is characterized by skin lesions that cause intense pain, odor, drainage and scarring.

The cause of HS remains unclear, and this limits the current treatment options. The current hypothesis is that there is a blockage in the hair follicle unit, which triggers the immune response. Amanda and her team have found that E-cadherin and p120, both important for skin integrity, are lost in HS-affected skin, and their project seeks to understand how this loss may contribute to the hair follicle breakdown and subsequent inflammation. If the link is proven it may provide novel approaches for treatment of HS.

Grant category: Research Grants in open competition

Year: 2022

Geography: Germany

Sarah Hedtrich, who is also Associate Professor at the Faculty of Pharmaceutical Sciences of the University of British Columbia, leads this project focusing on developing novel ways to treat genetic skin diseases through intra-skin delivery methods.

Skin diseases caused by specific genetic defects (genodermatoses) are often rare but can be severe and even life threatening – like epidermolysis bullosa. To cure such diseases, the genetic errors which cause the diseases would need to be corrected. In recent years there have been major advances in targeted gene editing – not least with the CRISPR/Cas system which allows for both tissue- and cell-specific correction.

However, while the skin is readily accessible it has two features which impede such treatment: Firstly, the skin’s barrier function makes efficient delivery difficult, and secondly, as the skin is an epithelium with rapid turnover of the cells, a persistent cure involving gene editing must reach the stem cells which lie at the base of the epidermis, the outer layer of the skin.

Sarah and her team, with expertise in both dermatology, gene editing and topical drug delivery, aim to develop such a delivery system for gene correction treatments using microneedles and nanocapsules, and will investigate its efficiency in both human skin samples and bioengineered skin (disease) models.

Grant category: Research Grants in open competition

Year: 2022

Geography: Denmark

The project by Tim Tolker-Nielsen aims to identify novel chemical compounds as potential drug leads for treating bacterial involvement in atopic dermatitis. The present project builds on findings from another LEO Foundation grant, which discovered a central factor, Sbi, responsible for the virulence (the ability to cause disease) of the bacteria Staphylococcus aureus in atopic dermatitis flares. As this factor appears to be unique to that bacterium it can be targeted with minimal impact expected on beneficial commensal (i.e. non-pathogenic) bacteria. Tim and his team will utilize existing libraries of chemical compounds to screen for lead candidates that can prevent the production of Sbi and which may be developed into a future treatment for atopic dermatitis flares.

Grant category: Research Grants in open competition

Year: 2021

Geography: USA

Among the biological treatments approved for the treatment of psoriasis, is ustekinumab, which is a monoclonal antibody targeting the shared p40 subunit of two cytokines, IL12 and IL23.

This project aims to improve psoriasis treatment by understanding why some psoriasis patients respond well to treatment with ustekinumab (responders) and others do not (non-responders). Interestingly, some non-responders to ustekinumab still respond well to inhibition of the IL23 pathway alone via the unique p19 subunit.

The pattern of differentially expressed genes among responders and non-responders may enable prediction of which intervention will be most beneficial for the individual patient. The plan is to compare single-cell transcriptomic analyses from both responders and non-responders to identify treatment response-linked gene expression patterns, so-called ‘endotypes’.

One size does not fit all for these biological therapeutics, and the goal is for the research to contribute to the development of a ‘companion diagnostic’, which is a diagnostic test used as a companion to a therapeutic drug to determine its applicability to a specific person, and thereby to personalized medicine in psoriasis.

Grant category: Research Grants in open competition

Year: 2021

Geography: United Kingdom

This project, led by Edel O’Toole, aims to give new insights into the rare genetic skin disease, steatocystoma multiplex (SM) that may contribute to the development of a new treatment for affected individuals.

SM is a debilitating and embarrassing disorder, which presents as multiple smooth, yellow skin lumps or cysts distributed on the arms, trunk, neck, and underarm area. The lesions usually appear in the teenage years and for the severely affected patients with 100s to 1000s of cysts, these are a major burden causing disability and pain with frequent inflammation often mimicking infection.

The most common genetic defect is found in the gene coding for Keratin 17, a protein expressed in nails, hair follicles, skin on the palms and soles, and in sebaceous glands. The cysts in SM are believed to arise from the lining of these glands. The team will use single cell RNA sequencing and look at gene expression in individual cells lining the cyst and from the surrounding tissue, to understand the genetic differences.  In parallel, the O’Toole group will engineer cells from the sebaceous gland with and without the defect in the Keratin 17 gene. These cells will be used to form 3D skin models and cysts that mimic SM. Finally, drugs that target pathways of interest identified from the RNA sequencing will be used to ‘treat’ the 3D model, thereby adding to the many insights around SM expected from this project.

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.