Explore our grantees and awardees

Grant category: Research Grants in open competition

Year: 2024

Geography: Austria

Georg Stary’s project aims to investigate interactions between T cells and structural cells, including keratinocytes, in the skin and how this cellular communication may affect the function of the T cells in dermatological diseases.

Human skin is protected by specialized T cells, called tissue-resident memory T cells (TRMs), which are needed to protect against infection at the site of pathogen encounter, but can also mediate inflammation in certain conditions. The exact regulation of TRMs in human skin is not well understood, hence TRM-targeted therapies are currently unavailable.

Georg Stary and his team have discovered that T cells communicate with structural cells of the skin via certain surface molecules and acquire a TRM phenotype after interaction with keratinocytes and fibroblasts. Some of the newly described molecules that instruct T cells to become TRM have not been implicated in the regulation of T cell tissue residency before.

Georg and his team aim to explore how structural cells of the skin instruct the maintenance of human TRM, and how this cellular crosstalk changes during inflammation. Based on preliminary data, they will unravel the function of certain co-receptors in TRM regulation using modern single-cell sequencing technologies on primary tissue from patients and ex-vivo co-culture systems with genetically engineered human cells. Based on this, they will subsequently test the therapeutic potential of targeting T cell-structural cell interactions in a humanized mouse model of TRM-mediated skin inflammation.

This study will not only inform about new mechanisms of human TRM instruction in health and disease and explore options for developing clinical applications targeting interactions with structural cells, but also form the basis for designing clinical studies to treat selected TRM-mediated diseases, such as graft-versus-host disease or psoriasis.

Grant category: Research Grants in open competition

Year: 2024

Geography: USA

The goal of Eliza Pei-Suen Tsou’s project is to understand the importance of aging endothelial cells (a cell type lining blood vessels) in scleroderma.

Scleroderma is an autoimmune disease characterized by inflammation, scarring of tissues and organs, including the skin, and changes in blood vessels throughout the body.

Most patients experience vascular abnormalities as one of the first symptoms, which trigger tissue stiffness and related complications later in the disease. Although these vascular changes are early critical events, the underlying cause of why they occur has not been determined.

Eliza Pei-Suen Tsou and her team found that dermal endothelial cells from scleroderma patients function differently compared to healthy controls. In particular, these cells undergo senescence, which is a process by which a cell ages but does not die off when it should. Over time, large numbers of senescent cells build up in the body. These cells remain active and release harmful substances that may cause inflammation and damage to nearby healthy cells.

In this project, Eliza and the team aim to determine the cause for vascular abnormalities in scleroderma, with a specific focus on how senescence is involved. They hypothesize that endothelial cell senescence is fundamental in causing the disease and might be targeted for therapy. Specifically, they propose that endothelial senescence accounts for the abnormality of endothelial cells in scleroderma, resulting not only in blood vessel changes but also in tissue scarring.

The goal is to determine why the endothelial cells acquire the senescent phenotype, and what this senescent phenotype does to promote the disease.

This project may form the basis for novel approaches to treating scleroderma.

Grant category: Research Grants in open competition

Year: 2024

Geography: USA

Christopher Bunick’s project aims to improve and substantiate our current knowledge of the structure and function of Janus kinases (JAKs) to improve safety and efficacy when developing new JAK inhibitors.

Janus kinase (JAK) inhibitors are small molecule drugs that treat inflammatory dermatological conditions by inhibiting cytokine signaling. Currently targeted diseases include atopic dermatitis, psoriasis, hand eczema, alopecia areata, vitiligo, and hidradenitis suppurativa.

Optimal JAK inhibitor matching to dermatologic disease remains challenging because of cross reactivity among four related JAK kinases: JAK1, JAK2, JAK3 and TYK2. Each possesses catalytic kinase (JH1) and allosteric (JH2) domains (an allosteric domain is a site where binding of a molecule indirectly modulates the function of the protein, here the catalytic activity). Both JH1 and JH2 domains have been targeted for drug development, yet a scientific knowledge gap exists as to how the allosteric JH2 domain regulates catalytic JH1 function and the subsequent downstream activation of signal transducer and activator of transcription (STAT) proteins.

A barrier for JAK inhibitor prescription is its promiscuity; it may target more than one JAK, leading to broader cytokine suppression than desired. This poor selectivity is likely rooted in suboptimal drug discovery procedures emphasizing inhibitory capacity over selectivity, resulting in unexpected real-world side effects, including malignancy, cardiovascular events, and thrombosis.

Christopher Bunick and his team will use AI-based generative modeling, molecular dynamics, computational biophysics, structural biology, and biochemistry to (i) determine how JH2 allosterically regulates JH1; (ii) define the structural basis for enhancing selectivity against specific JAK domains; (iii) elucidate downstream mechanisms regulating STAT signaling; and (iv) elucidate molecular properties of JAKs beyond JH1/JH2 domains.

This project may pave the way for better and safer treatment of skin diseases using JAK inhibitors.

Grant category: Research Grants in open competition

Year: 2024

Geography: USA

Julia Oh’s project aims to develop a novel and more physiological approach to studying how microbes interact with human skin cells and the effects of this interaction on overall skin health.

The human skin microbiome – encompassing hundreds of bacterial and fungal species – has essential roles in maintaining skin health. Skin microbiome dysfunction can contribute to diverse skin infections, inflammatory disorders, and skin cancer.

It is important to both identify the microbe–skin cell interactions that go awry in skin disease and to evaluate the therapeutic potential of new approaches for treating skin diseases. However, a detailed mechanistic understanding of how various skin microbes interact with human cells to maintain skin health or promote skin disease is currently lacking.

The goal of Julia Oh’s project is to determine how diverse skin microbes impact the essential functions of skin cells. However, there are few experimental models that allow us to investigate the diversity of skin microbes in a physiologically relevant way.

To enable a detailed investigation of microbe–skin cell interactions and their effects on skin health, Julia Oh and her team will model microbial colonization in cultured skin tissue that is genetically modified to investigate skin cell mechanisms. Then, using metabolomics and computational models, they will identify microbial metabolites to reveal microbial mechanisms.

This new approach could broadly enable biomedical researchers to determine how microbe–skin cell interactions impact skin functions, immunity, and susceptibility to diseases arising from microbial infection, and inform potential preventative and therapeutic strategies that harness the microbiome.

Grant category: Serendipity Grants

Year: 2023

Geography: Denmark

Vasileios Bekiaris will investigate how an observed adverse impact of a drug candidate in psoriasis may be converted to a potential treatment of cancer.

Vasileios Bekiaris and his team have been studying the mechanisms by which psoriasis is induced for several years, and their goal was to find ways to suppress it. They have discovered a molecule that is necessary for the generation and function of the immune cells responsible for causing psoriasis. Moreover, they have access to a drug that targets and neutralizes this molecule, and therefore they thought that it could potentially inhibit psoriasis. Contrary to what they expected, the drug induced inflammation and exacerbated psoriasis instead of treating it. It is known that for many cancers, inflammation promotes favourable protective immunity and helps the efficacy of immunotherapy. Using a mouse melanoma model, Vasileios Bekiaris and his team have managed to generate data suggesting that the pro-inflammatory drug could in fact suppress tumour growth.

Vasileios Bekiaris will therefore investigate the drug’s potential in cancer treatment and, if successful, may open possibilities for a new immunotherapy against skin cancers. Vasileios Bekiaris and his team also believe that this data will continue their contribution towards understanding how skin inflammation is mediated.

Grant category: Serendipity Grants

Year: 2023

Geography: Austria

Beate Lichtenberger investigates the mechanisms behind cutaneous calcinosis caused by over-activation of Hedgehog signaling in the dermis to improve treatment options.

Cutaneous calcinosis (CUC) is a debilitating condition characterized by the abnormal deposition of calcium salts in the skin and subcutaneous tissues, leading to pain, impaired mobility, and disfigurement. Despite its significant impact on patient quality of life, effective therapeutic interventions for CUC remain lacking, and there is no model system to study the disease. Beate Lichtenberger and her team serendipitously discovered that over-activation of Hedgehog (Hh) signaling in dermal fibroblasts leads to calcium precipitates and inflammation in limb and tail skin of mice, recapitulating the human disease

Beate Lichtenberger will elucidate the underlying mechanisms driving calcium deposition, inflammation, and tissue damage in cutaneous calcinosis. Furthermore, she will perform single cell RNA sequencing (scRNA-Seq) of human CUC tissue to assess which cell types apart from fibroblasts contribute to the pathogenesis and how

By advancing the understanding of the pathogenesis of CUC and developing targeted therapeutic strategies like repurposing of existing Hh inhibitors, Beate Lichtenberger’s project has the potential to revolutionize the treatment landscape and significantly improve the lives of individuals afflicted by this condition.

Grant category: Serendipity Grants

Year: 2023

Geography: Italy

Marta Giacomello aims to elucidate the role of a newly discovered mitochondrial fission protein in organelle maturation by exploring its impact on melanosome development and lipid droplet formation.

Melanogenesis, the process of synthesis and storage of the pigment responsible for skin color, melanin, occurs at specialized cell organelles named melanosomes. The mechanisms underlying melanin synthesis are not fully understood, but recent data suggest that mitochondrial physiology influences melanogenesis. Marta Giacomello and her team discovered that a mitochondrial fission factor, serendipitously found at the melanosome-mitochondria interface, controls the size of early melanosomes and melanin levels independently of its role in mitochondrial morphology.

The team aims to demonstrate that the identified mitochondria fission factor is a common regulator of organelle maturation, which exerts its specific effect based on its subcellular localization and interaction partners. They will first investigate its role in melanosome maturation, and then to generalize its function by extending the analysis to lipid droplets.

By elucidating how the identified fission factor switches from its mitochondrial to its melanosomal function, Marta Giacomello may generate milestone findings in the field of melanogenesis, and proof-of-concept evidence for its general role as a master regulator of organelles’ fission and maturation. Potentially, the results of this project could lead to breakthroughs in the fundamental understanding of cell biology.

Grant category: Serendipity Grants

Year: 2023

Geography: Denmark

Søren Degn will investigate a novel link between age-related B cells (ABCs) and cytotoxic CD8+ T cells.

Søren Degn and his team have discovered a new and unexpected link between a type of immune cells that normally produce antibodies (B cells) and a type of immune cells that are responsible for eliminating the body’s own cells when they are infected or become cancerous (CD8+ T cells). Their preliminary findings indicate that this link may play an important role when the immune system is erroneously activated, when an infection cannot be cleared, or when a cancer is established. It is not known which exact signals are responsible for the communication between these two cell types, and whether it occurs directly or via a third-party messenger. However, it is known that it occurs in the spleen, an important immune organ, which filters the blood and prevents infections, but also plays a critical role in autoimmune diseases.

The intention of Søren Degn is to understand the cellular and molecular mechanisms behind this novel link. An increased understanding may enable new therapeutic strategies in the future across a range of important diseases such as inflammatory skin disorders, autoimmune diseases, and cancer.

Grant category: LEO Foundation Dr Abildgaard Fellowships

Year: 2023

Geography: Denmark

Project title: Staphylococcus aureus drives inflammation and disease activity in atopic dermatitis – novel approaches to old problems 

Fellowship theme: Skin Immunology and Inflammatory Skin Diseases

Terkild Brink Buus’ vision is to develop better strategies to manage Atopic Dermatitis (AD) and improve patient lives by increasing our understanding and providing vital insights into the underlying biology. AD is a debilitating disease affecting more than 30% of Danish children at great cost to patients, parents, and society.

Terkild Brink Buus’s project addresses the role of bacteria and their toxins in causing severe worsening of the AD. Building on his expertise in complex data analysis and research on aberrant T cells and skin inflammation, Terkild Brink Buus will explore how T cells – a vital part of our immune system – are hijacked by bacterial toxins to aggravate AD and how this can be counteracted by novel treatments.

Terkild Brink Buus hopes to increase our understanding of how bacteria and their toxins affect the skin and worsen the symptoms of AD patients. His research will provide the basis for initiating clinical trials of new treatment approaches targeting bacteria in AD patients as well as guidelines for how to determine which patients are most likely to benefit. Finally, he will provide several novel laboratory and analytical techniques that will be of high value to future research within inflammatory skin diseases.

Grant category: LEO Foundation Dr Abildgaard Fellowships

Year: 2023

Geography: Denmark

Project title – ILnext: Unravelling the potential of ionic liquids as next generation cutaneous drug delivery systems

Fellowship theme: Skin Physiology and Cutaneous Drug Delivery

Stine Rønholt’s vision is to explore new ways to treat chronic skin issues (like eczema) directly on the skin. Today, such diseases are primarily treated by immunosuppressants, that upon systemic exposure can weaken the immune system. Atopic dermatitis is effectively treated by a type of medicine called JAK inhibitors, administered as tablets. Yet, direct administration of JAK inhibitors via the skin is hampered by the skin’s tough outer layer.

Stine Rønholt’s project will develop a new technology that treats eczema directly on the skin. To do so, Stine Rønholt is using a novel approach, “ionic liquids,” which can increase the drug solubility allowing for high dose treatment. Much like how sugar dissolves in water. This approach will help to deliver more medicine into the skin, targeting and treating eczema more effectively. Stine Rønholt’s goal is to figure out how to make this work for two specific JAK inhibitors, baricitinib and abrocitinib. Focus here is currently directed towards understanding how the ionic liquids used work together with the drugs, as well as what happens to the skin when the drug is applied. Even though the drug needs to be transported across the skin to where it is going to work, the technology should not cause any irritability to the skin. Special biophysical techniques are to be used to study all these things closely.

Stine Rønholt hopes to be able to deliver a high amount of medicine directly to a problem area without any uncomfortable procedures by using this approach. This could enhance treatment and lower the frequency of medicine required. Additionally, insights gained from Stine Rønholt’s project may pave the way for a new and improved method of addressing skin issues in a more efficient manner.