Grant category: Research Grants

Grant category: Research Grants

Year: 2025

Geography: USA

Darier Disease (DD) is an incurable skin disease caused by pathogenic variants in one copy of a calcium pump called SERCA2, sometimes accompanied by neuropsychiatric symptoms and seizures. The disorder typically appears in teenagers and comes and goes in response to various forms of stress, resulting in painful lesions due to loss of epidermal tissue integrity, vulnerability to infection, and loss of self-esteem. Even though the underlying genetic basis of DD was discovered >25 years ago, treatments are still limited to non-specific drugs with distressing side effects, antibiotics, and behavior modification. We identified a unique vulnerability of DD cells caused by their failure to turn on a metabolic pathway that protects normal cells against stress. We aim to revive this protective pathway to restore normal metabolism in DD cells, and in so doing, enhance tissue integrity and the ability to repair DNA and prevent damage to the remaining good calcium pump.

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.

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.

Grant category: Research Grants

Year: 2025

Geography: USA

Most vaccines and textbook models assume that special immune messengers called cytokines (such as IL‑6 or interferon‑α) are needed to tell T cells what to become. These cytokines are normally triggered by adjuvants in vaccines or by the immune system sensing pathogens. Our new findings overturn this view. We discovered that Langerhans cells—immune sentinels in the skin—can trigger strong antibody responses even in the steady state, when those cytokines are absent. Instead of relying on inflammatory messengers, they use surface “grip” proteins (integrins) to fine‑tune the conversation with T cells. This cytokine‑independent pathway may explain how the immune system quietly learns from the skin microbiome and maintains balance, while errors in this mechanism could underlie autoantibody diseases such as pemphigus or lupus. Our first goal is to confirm these findings. Once established, they will guide new strategies for vaccines or treatments that prevent chronic inflammatory skin disease.

Grant category: Research Grants

Year: 2025

Geography: USA

Human skin pigmentation is highly variable among world populations and determines skin sensitivity to ultraviolet radiation, susceptibility to skin cancer, vitamin D production, and other outcomes. Much of this variability is determined by genetics. Using genetic analyses among diverse native Africans, we and our collaborators linked skin pigment variation with levels of expression of a gene called TMEM138. Inactivating mutations in TMEM138 or about 200 other genes cause developmental disorders called ciliopathies in which the primary cilium – a cell structure not known to impact pigmentation – fails to form properly. This proposal seeks to use cultured skin pigment cells called melanocytes and reconstituted human skin to better understand the molecular mechanisms by which TMEM138 specifically, and the primary cilium more generally, regulates pigment formation. Our study will provide new insights into skin pigment physiology and diseases and into how ciliopathy classes differ.

Grant category: Research Grants

Year: 2025

Geography: Australia

Skin diseases affect millions worldwide, yet research and treatment often rely on animal models that do not fully capture human biology. In this project, we will use patient-derived stem cells to grow miniature 3D models of human skin, called organoids. These living models mimic how skin develops, functions, and responds to disease, allowing us to study rare genetic conditions directly in the lab. By comparing patient organoids with genetically corrected “healthy” controls, we will uncover the biological mistakes that cause disease and identify new treatment targets. We will also test whether these organoids can predict how patients respond to therapies, offering a path toward safer and more effective medicines. This research aims to set a new standard for dermatology by reducing reliance on animal experiments, accelerating drug discovery, and improving care for people living with severe skin disorders.

Grant category: Research Grants

Year: 2025

Geography: USA

Immunotherapy has transformed cancer treatment, helping the body’s immune system attack tumors. Unfortunately, these powerful drugs often cause side effects when the immune system also attacks healthy tissues. The skin is one of the most commonly affected organs, leading to rashes and other painful conditions that can force patients to stop life-saving therapy. Our project aims to understand why this happens. We recently discovered that certain immune cells, called CD8 T cells, are activated by bacteria living on the skin and then attack healthy skin cells during treatment. We will study how these bacteria and immune cells interact and test new ways to prevent this process. By uncovering how microbes trigger skin damage, our research could pave the way for safer cancer immunotherapies, helping patients stay on treatment longer while avoiding harmful side effects.

Grant category: Research Grants

Year: 2025

Geography: Switzerland

Chronic wounds or hypertrophic scars affect a large percentage of the population world-wide, but the therapeutic options are still limited. The development of innovative wound therapeutics requires a thorough understanding of the mechanisms underlying normal and impaired healing. This project will study a new regulatory mechanism in wound healing – the transfer of metabolically highly active cell organelles (mitochondria) between different cell types and the functional consequences for wound healing. We will use state-of-the art cell culture and mouse models to determine if mitochondrial transfer has beneficial effects on recipient cells and if this promotes the wound healing process. Through collaboration with clinical partners, we will determine the importance of our findings for normal and impaired healing in humans. The results will pave the way for the development of new wound therapeutics that target mitochondrial transfer or proteins regulated by this process.

Grant category: Research Grants

Year: 2025

Geography: Netherlands

Mycetoma is one of the world’s most neglected diseases – a slow growing skin infection that causes severe pain and deformities. It affects people in poor, rural areas across more than 20 countries, spanning five continents. The fungal form, eumycetoma, can lead to lifelong disability, and, in many cases, amputation. It is often accompanied by social stigma and mental health challenges, further isolating patients. Current treatments are toxic, unaffordable, and must be taken for up to a year – often with poor results. One major reason better treatments haven’t been developed is that there is no reliable way to test new drugs before trying them on humans. Wendy Laureijssen-van de Sande’s project will develop the first mouse model that closely mimics the human form of the disease. This will enable researchers to test new antifungal compounds more safely and effectively, laying the path for better, faster and more affordable treatments for patients who urgently need them.

Grant category: Research Grants

Year: 2025

Geography: Australia

Autoimmune bullous disease is a condition where the patient’s immune system attacks their skin, causing painful blistering. Some patients develop blisters in the mouth, leading to difficulty eating and malnutrition or inflammation in the eye, which can cause blindness. There is no cure. Treatment involves suppressing the immune system but can lead to side effects and increased infections. Joanne Reed’s research will use new technology to investigate patient blood and skin samples left over from biopsies performed for diagnosis. The technology enables patient samples to be evaluated at an unprecedented level of detail to identify and study the immune cells and genes responsible for disease. This information will be used to develop a test that can predict patients at risk of severe symptoms to enable early intervention before permanent organ damage occurs. The detailed analysis of the disease-causing cells will also inform the development of new drugs that can specifically target these cells.