Deciphering the role of Langerhans cells in the pathogenesis of cutaneous pain
Grantee: Clare Bennett, Professor, University College London, UK
Amount: DKK 3,324,751
Grant category: Research Grants in open competition
Year: 2024
Geography: United Kingdom
Clare Bennett’s project explores the skin’s sensory nerves. These protect us from harm, such as heat or toxins, yet little is known about how they are sustained. Psoriasis is a common disfiguring skin condition, where pain suffered by patients and its impact on mental health and quality of life are frequently overlooked. Understanding how sensory nerves are protected in healthy skin could reveal why this process fails in psoriasis, leading to pain. Langerhans cells (LCs), immune cells in the skin’s epidermis, are known for detecting infections. However, emerging evidence suggests that LCs may also perform non-immune roles that have not been thoroughly studied. This project aims to investigate how psoriasis changes the way LCs interact with the nerves in the skin. Clare Bennett and her team hypothesize that changes in psoriatic skin disrupt protective function, leading to uncontrolled nerve growth. Clare Bennett and her team combine expertise in immunology, neuroscience, and dermatology. They will use advanced microscopy, genetic models, and gene expression analysis in well-established lab models to study LC-nerve interactions and aim to validate their findings using psoriasis patient skin samples. The results of Clare Bennett’s project could fill critical gaps in our understanding of sensory nerve regulation. Ultimately, the hope is to uncover new strategies to reduce pain and improve quality of life for psoriasis patients and potentially those with other skin diseases.
Skin Genetics Consortium
Grantee: Lavinia Paternoster, Associate Professor, University of Bristol, UK
Amount: DKK 4,046,238
Grant category: Research Grants in open competition
Year: 2024
Geography: United Kingdom
Deep phenotyping of T regulatory cells in psoriatic arthritis highlights targetable mechanisms of disease
Grantee: Shoba Amarnath, Reader in Immune Regulation, Newcastle University
Amount: DKK 2,094,632
Grant category: Serendipity Grants
Year: 2024
Geography: United Kingdom
Shoba Amarnath’s project will investigate an unexpected link between regulatory T cells and the development of psoriatic arthritis (PsA).
In Shoba Amarnath’s original studies, based on her LEO Foundation Award in 2019, she sought to understand the role of immune cells in melanoma. As part of these investigations and to compare immune responses between cancer and autoimmunity, Shoba serendipitously found, through single-cell RNA and protein level analysis, that regulatory T cell (Treg) communication pathways with unconventional immune cells were significantly disrupted in psoriatic arthritis (PsA). This unbiased deep phenotyping specifically revealed a novel Treg specific regulatory mechanism in autoimmunity, especially crosstalk with osteoclast precursors (OCPs). It also has identified new targetable proteins in diseases where there is significant bone loss.
The LEO Foundation Award 2024 – Region EMEA
Grantee: Claire Higgins, Reader, Department of Bioengineering, Imperial College London, UK
Amount: USD 100,000
Grant category: LEO Foundation Awards
Year: 2024
Geography: United Kingdom
Dr. Claire Higgins, is a Reader in the Department of Bioengineering at Imperial College London in the UK,
She receives the award in support of her impressive academic achievements and her remarkable leadership within her research group and to future generations of skin scientists. Her research aims to achieve scarless wound healing in human skin by studying the human hair follicle and understanding how it can be used as a model for skin healing.
Impact of ageing on epidermal cell fate plasticity
Grantee: Maria Alcolea, Associate Professor, University of Cambridge
Amount: DKK 3,887,952
Grant category: Research Grants in open competition
Year: 2024
Geography: United Kingdom
Maria Alcolea’s project explores how the plasticity of skin cells is affected by aging. Maria Alcolea and her team will study the molecular pathways that modulate changes in cell behaviour throughout life. The ultimate aim is to identify new targets to improve tissue regeneration and delay the regenerative decline associated with human skin ageing.
The ability of epithelial cells to rewire their program of cell fate in response to tissue perturbations has emerged as a new paradigm in stem cell biology. This plasticity improves the efficiency of tissue repair by enabling differentiated/lineage committed cells to reacquire stem cell-like behavior in response to damage. However, despite obvious implications for skin regeneration, virtually nothing is known about how the plastic capacity of skin cells is affected by ageing, and whether this contributes to changes in the normal physiology of the epidermis at later stages in life.
Maria Alcolea’s project will investigate the impact of aging in skin cell fate plasticity by making use of a novel in vivo model that enables tracing the fate of epidermal cells from the earliest stages of commitment towards differentiation. Newly developed tools offers a unique opportunity to identify the mechanisms dictating epithelial cell fate plasticity and determine whether aged-associated changes in this process hold the key to understand why the regenerative capacity of our skin declines over time. She will combine the lab’s expertise in in vivo quantitative lineage tracing, single-cell RNA sequencing approaches, and mathematical network analysis. Observations made in in vivo mouse models will be compared to human skin using a novel 3D organ culture.
Maria Alcolea’s project may contribute significantly to the emerging field of epidermal cell plasticity and provide a benchmark for identifying potential targets to partially reduce/reverse skin ageing.
Scarless wound healing: exploiting the regenerative properties of the spiny mouse
Grantee: Sofia Ferreira Gonzalez, Fellow, University of Edinburgh
Amount: DKK 3,995,846
Grant category: Research Grants in open competition
Year: 2023
Geography: United Kingdom
Sofia Ferreira Gonzalez’s project aims to characterize the regenerative capacity of the spiny mouse – the only mammal known to fully regenerate skin with minimal scarring – to optimize future wound treatment in humans.
Skin fibrosis is often a sequela of suboptimal wound healing following significant epidermal and/or dermal injury (burns, trauma, major surgeries). Fibrotic material replaces native skin with dense, non-functional connective tissue, ultimately leading to loss of function. In its mildest form, fibrosis is a minor aesthetic problem, but in the most severe cases it can lead to debilitating skin pathologies that result in limited movement, high morbidity, and prevention of patient reintegration into society.
Current treatments for fibrosis include physical therapy and surgery, but there are no therapies that directly target the underlying cellular and molecular mechanisms of skin fibrosis.
The spiny mouse (Acomys) is, to date, the only mammal capable of skin autotomy (i.e., self-amputation of the skin to elude a predator’s grasp). Fascinatingly, the spiny mouse completely regenerates the lost skin and regrows cartilage and appendages (nails, hair) with minimal fibrotic response.
A multimodal approach addressing the mechanisms driving spiny’s scarless regeneration may provide novel therapeutic opportunities to treat and prevent skin fibrosis.
In this project, Sofia Ferreira Gonzalez and her team investigate three questions: 1) is the spiny mouse’s scarless regeneration depending on specific cell populations, circulatory factors or a combination thereof, 2) which specific pathways are responsible for the scarless regeneration, and 3) how can the research findings be translated into novel therapeutics to improve skin wound healing in humans?
Global Atopic Dermatitis Atlas (GADA)
Grantee: Carsten Flohr, King's College London
Amount: DKK 10,000,000
Grant category: Standalone grants
Year: 2023
Geography: United Kingdom
Atopic dermatitis, also called atopic eczema, or just eczema, is a non-contagious, chronic skin disease, causing dry, patchy, and itchy skin. It affects up to 20% of children and up to 10% of adults. Of all skin diseases worldwide, it is the most common type, with a burden that remains a significant challenge for the people affected, their families, and societies.
Despite progress made in treating severe forms of atopic dermatitis, there is a need for high-quality information showing how many people per country have atopic dermatitis and how severe it is. With strong data, atopic dermatitis can be better understood and treated.
With a grant from the LEO Foundation, the Global Atopic Dermatitis Atlas, or GADA, will help address gaps in current data by creating and maintaining a living online atlas, where the newest research-based knowledge and data on atopic dermatitis, its prevalence, severity, and treatment are available in one place – collected and analyzed in the same way for all countries.
About GADA
The Global Atopic Dermatitis Atlas (GADA) is a worldwide, long-term project. GADA is led by Professor Carsten Flohr (St John’s Institute of Dermatology, King’s College London, UK) and is an initiative established by the International League of Dermatological Societies (ILDS) in 2022 in collaboration with supporting stakeholders:
Skin bacteria lipopeptides: key modulators of keratinocyte immune responses and atopic dermatitis
Grantee: Peter Arkwright, Senior Lecturer, The University of Manchester
Amount: DKK 4,163,557
Grant category: Research Grants in open competition
Year: 2023
Geography: United Kingdom
Dr Peter Arkwright’s project aims to functionally characterize a group of recently discovered anti-inflammatory bacterial substances and investigate their potential therapeutic value in atopic dermatitis.
Staphylococcus aureus is unique in being the only bacterial species that consistently triggers flares in atopic dermatitis (AD). In previous work, also supported by the LEO Foundation, Dr Peter Arkwright, Dr Jo Pennock, and their team at the University of Manchester discovered “Sbi” as the unique factor produced by this bacterium that initiates AD in skin cells. Recently, they have identified factors produced by skin bacteria that completely block Staphylococcus aureus-induced AD, both in the lab and in an eczema mouse model. These factors are small, stable chemicals, made up of both fats and small proteins (lipopeptides).
In a collaboration with Professor Hiroshi Matsuda and Professor Akane Tanaka in Tokyo, Japan, they will apply lipopeptides derived from different bacteria to the skin of mice with AD to determine which are most effective at reducing the clinical dermatitis, itch, and skin damage. They will also explore how these factors work, using cell, protein, and lipid staining techniques. By purifying and characterizing these chemically stable immunosuppressive lipopeptides it is hoped that promising candidates identified here can be taken forward into clinical trials to develop novel therapies for AD.
The LEO Foundation Award 2023 – Region EMEA
Grantee: Dr. Lavinia Paternoster, Associate Professor, University of Bristol
Amount: USD 100,000
Grant category: LEO Foundation Awards
Year: 2023
Geography: United Kingdom
Dr. Lavinia Paternoster is Associate Professor at the University of Bristol in the UK.
She receives the award for her research pushing the boundaries of our knowledge on the genetic landscape of skin diseases. Lavinia Paternoster’s work has led to significant breakthroughs in the understanding of atopic dermatitis, psoriasis, and other complex human disorders.
Global Psoriasis Atlas Phase III (2023-2026)
Grantee: Professor Chris Griffiths, University of Manchester
Amount: DKK 11,160,157
Grant category: Standalone grants
Year: 2023
Geography: United Kingdom
Psoriasis is a life-long and currently incurable immune-mediated skin disease affecting more than 60 million people worldwide. In addition to its cutaneous, stigmatizing manifestations, the disease is associated with other major medical conditions including depression, cardiovascular disease, diabetes, arthritis and cancer and can be construed as life-ruining. As such it represents a significant public health challenge. Despite remarkable advances in treatment options in some parts of the world, psoriasis continues to affect the quality of life of patients and impact health economics negatively.
GPA Phase III (2023-2026)
The GPA Phase III is focused on continued improvement of the understanding of the epidemiology of psoriasis and its incidence and prevalence at the global level. This third phase aims to build upon the previous achievements of the GPA Phase II. Here ambitions include:
- An extensive update to the GPA’s large international dataset to create and launch edition 3 of the GPA.
- To strengthen collaboration with the dermatology work stream of the Global Burden of Diseases (GBD).
- To conduct new epidemiological studies to enhance the GPA.
- To conduct new studies to improve knowledge about the comorbid disease burden of psoriasis.
Background
With a mission to ‘ensure that people with psoriasis, wherever they live in the world, have access to the best available care’, Professor Griffiths and the University of Manchester initiated the development of a Global Psoriasis Atlas in 2016. The GPA is a long-term iterative project, which was initiated in close collaboration with the WHO and international dermatology and psoriasis organisations.
The LEO Foundation has been main funder of the development of the 1st edition of the GPA through a 3-year grant of DKK 6,370,000 from 2017 – 2020. The GPA project has in its first period (GPA Phase I) focused on research into the global prevalence and incidence of psoriasis – with the 1st edition of the GPA website launched on World Psoriasis Day 29 October 2019.
The LEO Foundation was also the main sponsor of GPA phase II, with a three-year grant of DKK 8,000,000 from 2020-2022. In this phase, the atlas-initiative has had a special focus on increasing its global outreach, including studies of psoriasis in Latin America, Malaysia, and Taiwan as well as on increasing and validating data on the association of psoriasis and cancer. Another important element of Phase II was to design and test a clinical diagnostic tool for health-care professionals globally, taking into account the different expressions of the disease, depending on skin colour.