Factors maintaining tertiary lymphoid aggregates in Discoid Lupus Erythematosus

Grantee: Timothy Vyse, Professor, King's College London, UK

Amount: DKK 3,941,580

Grant category: Research Grants

Year: 2025

Geography: United Kingdom

Discoid lupus (DLE) is an autoimmune disease giving rise to disfiguring facial lesions, with limited drug options. DLE lesions contain dense accumulations of B and T lymphocytes, but the reasons they develop, persist and recur is currently unknown. DLE’s systemic counterpart, SLE, affects many organs throughout the body. We can utilise the overlap between these related conditions to ask whether similar mechanisms might operate in both DLE and SLE. In systemic lupus, engagement between co-stimulatory molecules on the T and B cell surface drives B cell survival and produces a co-stimulatory effect. We will investigate whether a similar mechanism operates in lesion-resident B cells to promote lesion persistence and identify the cell surface molecules implicated. We will discover whether specific immune cofactors in the skin prevent cessation of the costimulatory signal. If successful, blocking co-stimulatory signals on B cells from DLE may provide the basis of future drug discovery.

Decoding the evolution of anti-fungal immunity in the human skin

Grantee: Christina Zielinski, Professor, University of Cambridge, UK

Amount: DKK 3,985,414

Grant category: Research Grants

Year: 2025

Geography: United Kingdom

Fungal skin infections affect up to a quarter of people worldwide. They can also recur, spread and become life-threatening, especially in immunocompromised patients. This shows that our immune system does not always develop lasting and efficient protection. In particular, we don’t know why protective immune memory works so well against viruses but fails against fungi. Our project will study how special immune cells called T cells respond to fungal infections in the skin. By following patients with fungal skin infections over time, and comparing skin and blood samples, we will track how these immune cells are generated, maintained, or lost and what molecular weapons they use to fight the infection. We will use state-of-the-art and unique methodologies from our laboratory, allowing in-depth analysis of millions of T cells simultaneously at single-cell resolution. These insights could reveal new ways to strengthen our natural defenses and lay the foundation for future therapies.

Dissecting the role of the ageing tissue microenvironment in inflammatory immune responses within human skin

Grantee: John Connelly, Professor, Queen Mary University of London, UK

Amount: DKK 3,501,669

Grant category: Research Grants

Year: 2025

Geography: United Kingdom

The normal healthy functions of our skin significantly decline with age, and these changes increase the risk of infection, chronic wounds, inflammatory diseases, and cancer. Therefore, understanding the biological mechanisms underlying skin ageing is essential to protect against age-related diseases and maintain healthy skin function. The aim of this project is to dissect the cellular, biochemical, and mechanical processes of skin ageing and to directly test how they impact key functions, including tissue homeostasis and immunity. We will take advantage of state-of-the-art imaging and genomic methods available within our institution to profile the ageing process, and advanced 3D culture models of human skin will be used to test key genes and biochemical pathways. The results will provide fundamental insights into human skin ageing, and over the long term, they have the potential to identify key therapeutic targets for counteracting or preventing age-related skin diseases.

A 3D printed solution to the Fingertip Unit problem

Grantee: Oisín Kavanagh, Senior Lecturer, Newcastle University, United Kingdom

Amount: DKK 1,293,996

Grant category: Research Grants

Year: 2025

Geography: United Kingdom

Medicated creams and ointments are used to treat millions of people every day. Despite this, inconsistent drug delivery remains a long-standing issue. While Finlay’s Fingertip Unit was introduced in 1973 to address this gap, there is still a challenge in delivering consistent doses of topical medicines for small lesions, such as those seen in paediatrics. This issue is particularly relevant today with the introduction of incredibly potent topical medicines. Oisín Kavanagh’s project aims to design an adjustable adapter that enables patients to accurately control the amount of medication they apply to their skin. During the design process, Oisín Kavanagh and his team will collaborate with patients and their carers to ensure that this product meets their needs.

Skin bacteria control of sensory function in response to environmental perturbations

Grantee: Simone Di Giovanni, Professor, Imperial College London, United Kingdom

Amount: DKK 3,997,382

Grant category: Research Grants

Year: 2025

Geography: United Kingdom

Skin innervation is our sensory interface with the ever-changing environment undergoing fluctuations in temperature and humidity. Sensation needs to account for these fluctuations to regulate sense of touch, pain, movement, learning and memory, sexual and social conduct. More than 100 million bacteria that reside on the human skin are the first line of response to environmental perturbations. Variable humidity, salinity, temperature, and oxygen affect bacteria metabolism and diversity. Simone Di Giovanni therefore hypothesise that bacteria are required for sensory function affecting complex behaviours in response to perturbations in temperature and humidity. This bears implications for human physiology, health and resilience on earth.

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

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

Year: 2024

Geography: United Kingdom

This project concerns establishing a consortium for research in the genetics of skin diseases, which are the 4th leading cause of disability globally. Lavinia Paternoster and the group behind the Skin Genetic Consortium (SGC) will use population-scale genomic datasets from across the globe to conduct well-powered human genetic studies to discover disease mechanisms, identify and prioritize drug targets, and improve the accuracy and utility of skin disease diagnoses for epidemiological research. Recent years have seen a dramatic increase in the number and diversity of population biobanks across the globe. The SGC will leverage these resources to undertake genome-wide association studies for an extensive set of skin conditions. Sample sizes in excess of 4 million will increase power for gene discovery in many previously understudied skin conditions. Furthermore, cross-disease analyses will be performed to identify shared disease mechanisms, potentially revealing drug re-purposing opportunities. The SGC brings together experts in genetic epidemiology, clinical dermatology and cohort custodians. This first phase of the SGC will uncover key biological insights and drug target evidence for an initial set of common skin conditions.

The project aims to generate a platform for uploading and harmonizing data, performing streamlined genetic analysis and open distribution of results. With further funding the SGC will expand to increase participant diversity, extend analyses to rare variants and generate additional molecular functional genomics data for experimental validation and clinical translation of results.

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

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

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?

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

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.