Explore our grantees and awardees

Grant category: Research Grants in open competition

Year: 2022

Geography: United Kingdom

The aim of Michael Simpson’s project is to identify potential cellular or molecular targets for acne treatment, based on analysis of genetic variation found in a large pool of acne patients.

Acne vulgaris is a very common skin disease which is characterized by clogging and inflammation of the pilosebaceous unit, which consists of a sweat gland and a hair follicle including the hair itself. While various potential causes leading to the disease have been investigated over the years, the underlying disease mechanisms have not yet been sufficiently elucidated. One common approach to learning more about cellular and molecular causes for development of disease in some people is to investigate changes in the genes that influence the behavior and communication paths of cells – the signaling cascades known to be involved in the disease. Michael and his team have previously identified several areas (loci) in the human genome which are associated with acne.

They now want to study these areas in further detail to better understand the causal molecular and cellular events that lead to acne and hopefully identify targets for treatment. They will use a three-step approach. Firstly, by identifying the genetic variants linked to the disease by analyzing genetic data from more than 60,000 individuals with acne. Secondly, they will cross-link these variations to create a map of the signaling pathways and associated cells responsible. Finally, based on this mapping, they expect to be able to identify targets for future treatments of the disease. If successful, the results may provide the first steps towards a better and more targeted treatment for this very common and socially stigmatizing skin disease.

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: 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.

Grant category: Research Grants in open competition

Year: 2021

Geography: United Kingdom

The aim of this project is to enable quantification of the effects of treating atopic dermatitis (AD) with new therapies. New therapies have similar effectiveness to steroids but are much more expensive. Thus, there is a need for demonstrated benefits and better long-term safety to persuade healthcare providers to fund them.

Optical coherence tomography (OCT) is an ideal tool to quantify the benefits of new drugs for treating AD, whilst checking that they do not cause skin thinning, which is a risk with long-term use of steroids. OCT is a non-invasive imaging technique that uses laser light to provide ultrasound-like images with higher resolution – and OCT avoids the need to perform painful biopsies.

One problem with the current OCT systems is that if the skin inflammation becomes too high, it becomes difficult to quantify because OCT can only image to depths of around 1 mm. This limited depth penetration can potentially be improved by using a longer wavelength of laser light. With the project, Stephen Matcher will quantify the improvement in OCT image quality when using 1600 nm light rather than the current 1300 nm light.

If successful, the project holds a strong potential for use in both clinical trials and clinical practice with a highly needed more patient-friendly tool for measuring drug efficacy in skin diseases such as atopic dermatitis.

Grant category: Research Grants in open competition

Year: 2020

Geography: United Kingdom

The aim of this project is to investigate why skin in the facial region heals faster and often with less scarring than the rest of the body but are still prone for other fibrotic diseases like keloid scars. 

Tanya Shaw hypothesizes that this is due to the dermal cells of the face being of a different origin than cells at other sites of the body. Dermal cells of the face stem from so-called neural crest cells and these cells are known for their fast migration and capacity to develop into a multitude of differentiated cells.   

The approach of the project will be to:  

1. investigate the genetics and epigenetics of keloid scars to determine to what extent they originate from neural crest cells  
2. compare neural crest cell-derived fibroblasts to fibroblasts from other origins in term of plasticity and cell migration  
3. manipulate the neural crest cell features in a mouse wound model to investigate if they are critical for wound healing and scarring.   

If the hypothesis can be confirmed, the project holds a strong promise for improvement of wound healing and scarring.   

Grant category: Research Grants in open competition

Year: 2020

Geography: United Kingdom

The ultimate goal of this project is to contribute to the development of new medicines to treat bacterially induced eczema.

The project is a continuation of previous work supported by the LEO Foundation on the impact of bacterial infection, specifically caused by Staphylococcus Aureus (S. Aureus), on eczema. Here, a single factor secreted by S. Aureus was identified as the primary causative agent for eczema development or flare-up. Furthermore, it was also found that the naturally occurring variant, S. Epidermidis, has an inhibitory effect on eczema-induction.

The objective of the present project is to further elaborate on the disease-preventing effect of S. Epidermidis. First, the team will identify any factor(s) secreted by S. Epidermidis that inhibits eczema and then confirm its role by knocking out any relevant gene(s). Finally, the effect of any identified factor(s) on S. Aureus-induced eczema will be studied.

Grant category: Standalone grants

Year: 2020

Geography: United Kingdom

Psoriasis is a significant, life-long and currently incurable skin disease, which, according to the first edition of the Global Psoriasis Atlas (GPA), affects at least 60 million people worldwide.

The need to understand and uncover how psoriasis impacts both the individual and society at large is in demand. The Global Psoriasis Atlas is a long-term project that seeks to become the ‘go-to’ evidence-based resource within the understanding of psoriasis and its effects on people and society all over the World.

GPA Phase II (2020-2023)

The GPA Phase II  is focused on continued research to establish robust data that address existing knowledge gaps within psoriasis on epidemiology, improving diagnosis, comorbid disease and economic impact.

Furthermore, if sufficient and robust data are available, the plan is to perform a pilot implementation study as part of GPA Phase II.

Addressing these key areas and how they differ between countries and regions will support the aim to provide better access to care for people with psoriasis worldwide.

Background

With a mission to ‘ensure that people with psoriasis, wherever they live in the world, have access to the best available care. The grant for the first version of the GPA was granted to Professor Griffiths and the University of Manchester in 2016.

The LEO Foundation has been main funder of the development of the first edition of the GPA through a 3-year grant of DKK 6,370,000 from 2017 – 2020. The GPA project has in its first three years focused on research into the global prevalence and incidence of psoriasis – resulting in the first edition of the GPA website which can be accessed free of charge here: Global Psoriasis Atlas online

Grant category: LEO Foundation Awards

Year: 2019

Geography: United Kingdom

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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Grant category: Research Grants in open competition

Year: 2019

Geography: United Kingdom

There is a sterile inflammatory response to needle challenge driven by recruitment of inflammatory monocytes to the skin in old humans. This inflammatory response negatively correlates with cutaneous immunity after injection of varicella zoster virus antigens into the skin. Inhibition of the inflammation associated with the injury response, with a p38-MAPkinase inhibitor, reduced inflammatory monocyte recruitment and significantly enhanced antigen-specific immunity.

The aim of this project is to understand how inflammation and inflammatory monocytes inhibit antigen-specific T cells in the skin of old human volunteers.

The following experimental questions will be addressed: 1) Which cells are responsible for the inflammatory response to needle injury and how does the interaction between the infiltrating monocytes and other inflammatory populations amplify the response? 2) How are the inflammatory monocytes recruited to the site of challenge in the skin? 3) How do the recruited monocytes inhibit antigen-specific immunity in vivo in the old? 4) Using biobanked skin biopsy samples before and after the same older subjects have been treated with Vitamin D, we will determine gene expression signatures of how this treatment enhances cutaneous antigen-specific immunity.

These investigations will identify ways to enhance the immunity of older humans to vaccination and also infection and malignancy.