Grant category: LEO Foundation Dr Abildgaard Fellowships

Grant category: LEO Foundation Dr Abildgaard Fellowships

Year: 2024

Geography: Denmark

Project title: Checkpoint receptor pathways as new targets for the treatment of skin fibrosis

Fellowship theme: Advanced Therapeutics Research in Skin Diseases

Skin fibrosis results in thick and stiff skin with a limited barrier function. This causes an increased risk of infections, pain and reduced function. No cure is available, and treatment options are limited. Stinne Ravn Greisen’s vision is to improve the treatment of skin fibrosis. To do this, she will advance our understanding of how the immune system and its regulatory pathways contribute to the development of skin fibrosis.

Skin fibrosis is a result of a complex interplay between an overactive immune system and excessive production of proteins supporting the connective tissue. This is exemplified in the systemic autoimmune disease scleroderma, and in localized keloid scarring. She hypothesize that immune regulatory pathways play a central role in the development of skin fibrosis, and in this project, she will: 1. Investigate fibrosis in skin samples from scleroderma skin, keloid scars and healthy volunteers, where she will focus on how immune regulatory pathways affect the interaction between immune cells and production of connective tissue material. 2. Establish a skin model to test potential new treatment options, and to understand how the immune cells work in a complex environment. 3. Use a mouse model to better understand the development of skin fibrosis and to test potential new treatment options.

The complex interaction between the immune system and fibrosis development is still poorly understood, which explains the limited treatment options for skin fibrosis. Stinne Ravn Greisen’s project will contribute to a detailed understanding of the immune mechanisms contributing to skin fibrosis. This knowledge is essential to develop new and better treatments. The outcome of her project will benefit patients with skin fibrosis as a result of scleroderma or keloid scarring but will also increase our fundamental understanding of the fibrotic process which is involved in multiple conditions including systemic inflammatory diseases, cancers, and cardiovascular diseases.

Grant category: LEO Foundation Dr Abildgaard Fellowships

Year: 2024

Geography: Denmark

Project title: Personalized medicine in dermatology: Algorithm assisted early identification of high-risk patients with hidradenitis suppurativa – initiation of prompt treatment in order to avoid disease progression

Fellowship theme: Systems Medicine in Dermatology

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that causes the formation of painful, impairing and suppurating boils. It plagues 1% of the global population at great cost to both the individual and society. While effective treatments exist, the most effective forms are expensive, and their use is restricted to patients with severe disease. Building on his expertise within clinical research, complex data analysis of genetic and environmental risk factors and construction of temporal disease trajectories, Rune Andersen’s research initiative aims at providing HS patients with individual risk assessment of disease progression and development of severe comorbidities.

Rune Andersen’s vision is to initiate personalized medicine within dermatology by creating a tool that can identify HS patients with a high risk of disease progression so that prompt preventive treatment at an early stage can be initiated.

To do so Rune Andersen and his group will take advantage of large established clinical cohorts, and through state-of-the-art techniques within datamining, clinical epidemiology, population genetics, and molecular biomedicine, he will uncover risk factors of individual disease progression and the development of severe comorbidities. This information is to be used to develop and validate predictive algorithms that can help in the transition from treatment to prevention.

Completion of this project will allow Rune Andersen to transition from standard of care to personalized medicine within HS by focusing on prevention of disease progression and comorbidity development rather than treatment. This will improve both patient welfare, and public resource-management and expenditures.

Grant category: LEO Foundation Dr Abildgaard Fellowships

Year: 2024

Geography: Denmark

Project title: Optimizing treatment of psoriasis

Fellowship theme: Systems Medicine in Dermatology

Nikolai Loft’s project is dedicated to revolutionizing the treatment of psoriasis by personalizing approaches based on individual patient characteristics and needs. The focus is on determining the underlying reasons why some patients experience a loss in the effectiveness of their treatment and whether treatment of psoriasis can prevent the onset of psoriatic arthritis (PsA). By identifying predictive markers for these conditions, Nikolai Loft’s project aims to tailor treatment plans that maintain effectiveness over time and mitigate the risk of PsA and thereby improve patient outcomes substantially.

Nikolai Loft plans to identify markers that can predict loss of treatment response in patients with psoriasis and markers that can predict development of PsA. The project will capitalize on Denmark’s unique data infrastructure integrating national registries with bioresources. This will involve thorough characterization using existing registry data and additional in-depth immunological and genetic profiling using new biological samples from more than 1000 patients with psoriasis. Additionally, Nikolai Loft and his research group will, based on these findings, assess the PsA protective properties of treatments of psoriasis. The end goal is to develop models that can identify patients at risk of treatment failure or developing PsA enabling adjustments of treatment strategies to mitigate these risks.

Nikolai Loft hopes to be able to reduce the incidence of treatment failure and enhance the quality of life for individuals with psoriasis by enabling more stable and effective treatment regimens. By doing so, he hopes to decrease healthcare costs associated with switching therapies. In the long term, by preventing PsA, this research project seeks to reduce the overall burden of psoriasis and its complications. Ultimately, tailoring treatment to the individual patient’s needs.

Grant category: LEO Foundation Dr Abildgaard Fellowships

Year: 2024

Geography: Denmark

Project title: Uncoupling the contribution of systemic and site-specific immunity in inflammatory skin disorders

Fellowship theme: Advanced Therapeutics Research in Skin Diseases

Patients with skin diseases can often suffer from other conditions like asthma, arthritis and inflammatory diseases of the intestines, suggesting that these diseases may be linked by a common cause. Importantly, there is currently no tool that can be used in the clinic to measure skin disease activity regularly. In the skin, resident memory T cells (TRM) can reside for years, providing protection to old and new infections, but at times, causing inflammatory skin diseases. A portion of these cells are thought to migrate through our bodies via the blood and there is the possibility that these inflammatory T cells can land in other organs and cause disease. Finding these rather rare inflammatory T cells has been difficult.

Wenning Zheng’s research project will focus on using the blood of healthy people and patients with eczema, psoriasis, and psoriatic arthritis (PsA) to find these rare aggressive T cells. Using sensitive new assays and building on her expertise as a computational immunologist, her group at LEO Foundation Skin Immunology Research Center will employ high resolution single cell T cell clones sequencing on donor-matched blood and tissues to understand the propensity for T cells to circulate from the skin, through the blood and into other organs. Since T cells quite specifically recognize antigens through a highly-diverse receptor on their cell surface, Wenning will characterize the diversity of these receptors and combine machine learning and wet-lab methods to identify the nature of antigens that are detected by T cells. It is hoped that by understanding the precise antigens that T cells see, we can develop tools to diagnose and treat skin diseases with greater precision.

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.

Grant category: LEO Foundation Dr Abildgaard Fellowships

Year: 2023

Geography: Denmark

Project title – T-cell derived extracellular vesicles constitute pro-inflammatory packages that drive disease progression in psoriasis

Fellowship theme: Skin Immunology and Inflammatory Skin Diseases

Aida Hansen’s vision is to improve the treatment options for psoriasis patients by contributing to a more detailed understanding of the cellular cross-talk mediating the inflammatory processes in the disease. She aims to investigate a novel concept for cellular cross-talk, mediated by vesicular structures known as extracellular vesicles (EVs), that may drive inflammation in psoriasis.

Aida Hansen’s project builds upon knowledge that psoriasis is mainly driven by pro-inflammatory cytokines, and recently, it was discovered that cytokines are partly packaged into EVs. She hypothesizes that the majority of cytokines implicated in psoriasis are carried in specific subsets of EVs constituting “pro-inflammatory packages”. She will: 1) Do an in-depth investigation of the packaging of cytokines into EVs derived from patients with severe psoriasis, 2) Investigate the functional impact of specific EV-subpopulations in driving the inflammatory response in psoriasis, and 3) Explore the therapeutic concept for neutralizing specific disease-promoting EVs in psoriasis.

Aida Hansen hopes to contribute to a deeper understanding of how cytokines are being transported between cells and the potentially different biological properties of soluble cytokines compared to cytokines packaged into EVs. This is still poorly understood. The outcome of her project may lead to identification of new inflammatory pathways and novel depletion strategies for innovative therapeutic interventions to alleviate symptoms and improve the quality of life for patients with severe psoriasis.