Viral hijacking of embryonic signaling pathways in trichodysplasia spinulosa

Grantee: Andrzej Dlugosz, Professor, University of Michigan, USA

Amount: DKK 3,985,000

Grant category: Research Grants in open competition

Year: 2024

Geography: USA

Andrzej Dlugosz’s project explores how a skin-associated virus called TSPyV can cause a striking hair follicle disorder called trichodysplasia spinulosa. In patients affected by this condition hair follicles on the face and ears are enlarged, structurally abnormal, filled with TSPyV viral particles, and produce spikes instead of hairs. To understand how TSPyV disrupts hair follicle biology Andrzej Dlugosz and his group created genetically engineered mice that express TSPyV viral proteins in skin. These mice produced enlarged and abnormal-appearing follicles and developed follicle-like structures in hairless areas, suggesting that TSPyV can somehow reprogram skin to drive growth of hair follicles which are needed for large-scale virus production. In keeping with this concept, one of the TSPyV viral proteins triggers abnormal activation of an important molecular signal that regulates formation and maturation of hair follicles. The studies will examine hair follicles in trichodysplasia spinulosa using powerful new molecular technologies to better understand the alterations in behavior and maturation of follicle cell types in this disease. They will also investigate how a specific TSPyV protein hijacks an important hair follicle signaling pathway, contributing to the profound changes seen in the skin of trichodysplasia spinulosa patients.

The results of the project have the potential to yield new insights into the regulation of molecular signals controlling formation and growth of hair follicles, based on findings from studying this rare condition.

Langerhans cells (LC) as main drivers of vitiligo: potential targets for novel therapeutic approaches with chemically enhanced RNA aptamers

Grantee: Julián Valero, Assistant Professor, Aarhus University, Denmark

Amount: DKK 3,999,441

Grant category: Research Grants in open competition

Year: 2024

Geography: Denmark

Julián Valero’s project explores an innovative approach for targeted drug delivery into the skin through the utilization of RNA aptamers (RNA snippets that are capable of binding to specific targets with high affinity and specificity). In collaboration with Patrizia Stoitzner and Helen Strandt (Medical University Innsbruck), Steffen Thiel (Aarhus University), Claus Johansen (Aarhus University Hospital) and Niels Schaft (University Hospital Erlangen), Julián Valero and his team will develop chemically modified RNA aptamers to target Langerhans cells (LC) or to block immune responses, aiming to develop treatment options for the autoimmune disease vitiligo. This disease is characterized by the infiltration of autoreactive cytotoxic T cells into the skin causing destruction of melanocytes important for producing skin pigments as UV-protection shield. The project will explore different approaches to dampen the autoimmune process during vitiligo, including the potential of local delivery of (i) anti-inflammatory molecules, (ii) antigenic peptides to reprogram CD4+T cells to regulatory T cells and (iii) immuno-blocking aptamers.

This project may enable development of innovative skin vaccination strategies and local anti-inflammatory treatment. Ultimately, this research holds the potential to alter skin-targeted therapies, enhance immune responses, and mitigate off-target effects by cell-specific delivery of novel vaccines.

Ex Vivo Culturing of the Human Skin Microbiome

Grantee: Beth McLellan, Professor, Albert Einstein College of Medicine, USA

Amount: DKK 4,054,452

Grant category: Research Grants in open competition

Year: 2024

Geography: USA

Beth McLellan’s project, in collaboration with co-PI and Kosaku Shinoda, explores the functional interactions of live or viable bacteria within the skin microbial community, and their implications in skin disease. The project aims to develop a robust ex vivo model, Skin Microbiome in a Test tube (SMT), to study the dynamic biochemical activity of the viable skin microbiome. Preliminary data indicate that the prototype version of the SMT system (v1) is capable of preserving the diversity of skin bacteria ex vivo. The aims are to (1) refine SMT using Propidium Monoazide (PMA) sequencing to exclusively replicate the viable microbiome and (2) investigate the impact of skin microenvironmental factors (e.g., moisture, sebum levels, and skin breakdown) on the composition and biochemical activity of the viable microbiome, using data from non-invasive sensors at multiple skin sites.

With the generation of the improved version of the SMT (v2), the project hopes to create an innovative platform for functional skin microbiome studies, drug screening and pharmacokinetic modeling with an emphasis on microbial viability leading to individualized treatment strategies based on microbiome community profiles. SMT will serve as a foundation for identifying biomarkers, developing microbiome-based therapies, and improving pharmacokinetic predictions.

Early protein biomarkers in childhood atopic dermatitis

Grantee: Ann-Marie Schoos, Clinical Research Associate Professor, Herlev and Gentofte Hospital/COPSAC, Denmark

Amount: DKK 3,501,080

Grant category: Research Grants in open competition

Year: 2024

Geography: Denmark

Ann-Marie Schoos’ project explores atopic dermatitis (AD), which affects about 1 in 5 children. The disease burden of AD varies; some outgrow their disease while others have persistent symptoms. The reasons behind these different outcomes are not well understood and are not addressed by current treatments. Biological markers (biomarkers) can help us understand the disease better and, ideally, help predict, prevent, or treat it more effectively. Proteins can be used as biomarkers and appear in the blood due to secretion or cell damage. While there have been studies identifying such biomarkers (using proteomics) in adults, there is limited research on children, especially in relation to the early stages of AD. To understand the processes involved in early development of AD, Ann-Marie Schoos’ project will explore a novel, large-scale panel of blood-borne proteins measured before and after disease development (at birth, 6 months, 18 months, and 6 years of age) in the well-characterized COPSAC2010 cohort. The children of this cohort have been followed intensely throughout childhood with longitudinal (i.e., over time) measurements of inflammation, allergy, immune data, and genetics among others.

Ann-Marie Schoos’ project hopes to show that a simple blood test in early childhood can predict which children are at high risk of developing AD and who will have a severe and persistent disease course. This could lead to personalized prevention or treatment strategies, improving the quality of life for these children.

Defining how skin microbial communities shape T cell function using a novel antigen-tracking technology

Grantee: Erin Chen, Assistant Professor, Broad Institute of MIT and Harvard, USA

Amount: DKK 3,929,293

Grant category: Research Grants in open competition

Year: 2024

Geography: USA

Erin Chen’s project aims to address the fundamental question: how do we translate the composition of our body’s colonizing microbes (our microbiome) into insight about immune function? Commensal bacteria (commonly known as just “commensals”) colonize our skin, over our entire lives, and generate the vast majority of microbe-host encounters, with largely unknown consequences. Erin Chen’s project focuses on commensals’ interactions with T cells because these cells critically impact many aspects of health and disease. Unlike infections, where a single pathogen invades into the tissue, commensals colonize within complex communities and communicate to the host immune system across an intact skin barrier. How the immune system decodes signals from each member of this community is unknown. Erin Chen and her team will address this by colonizing mice with defined communities of commensals and tracking the commensal-derived antigens along with the strain-specific T cells. To do this, they will develop novel methods to detect commensal-derived antigens within the host tissue, at high resolution. By varying the abundance and composition of community members, they aim to discover novel antagonistic, synergistic, and emergent properties of commensal-specific T cells. This work will provide visibility into a currently invisible process: how a lifetime of commensals on our skin are constantly sculpting our T cell function, which ultimately impacts our susceptibility to infections, autoimmunity, and cancer.

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

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.

Researchers Communicate (Forskerne Formidler)

Grantee: Vibeke Hjortlund, Videnskab.dk

Amount: DKK 2,500,000

Grant category: Education and Awareness Grants

Year: 2024

Geography: Denmark

Videnskab.dk will further develop the existing initiative Forskerne Formidler (Eng. Researchers Communicate), now with an expanded international focus. The overall purpose of Forskerne Formidler is to provide easy access for the public to the science that shapes the world, directly from the scientists themselves. With a continuation of the program and platform it will focus on the development of three different areas: new genres and improvement of quality for existing, courses and training in dissemination for scientists, and international distribution, collaboration and network within academic journalism.

Videnskab.dk is Denmark’s leading popular science media with around 1 million monthly users. The media is an independent source of daily science news, features and other quality content in many different formats.

Forskerne Formidler is supported by the LEO Foundation alongside the Novo Nordisk Foundation, the Lundbeck Foundation, and the Augustinus Foundation.

Read more about Forskerne Formidler

Dr Abildgaard Fellowship 2024

Grantee: Stinne Ravn Greisen, Assistant Professor, Dept. of Biomedicine, Aarhus University

Amount: DKK 12,000,000

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.

Dr Abildgaard Fellowship 2024

Grantee: Rune Kjærsgaard Andersen, Postdoc, Dept. of Dermatology and Allergy at Herlev and Gentofte Hospital, Copenhagen University Hospital

Amount: DKK 12,000,000

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.