Aplasia cutis pathogenesis provides key insights into skin and skin appendage biology

Grantee: Alexander Marneros, Associate Professor of Dermatology, Massachusetts General Hospital, United States

Amount: DKK 3,998,854

Grant category: Research Grants in open competition

Year: 2025

Geography: USA

To elucidate novel mechanisms that orchestrate skin formation Alexander Marneros have focused on a genetic skin disease that manifests with scalp skin wounds at birth, aplasia cutis congenita (ACC). Alexander and his team found that the genes KCTD1 and KCTD15 are mutated in patients with ACC. These genes form a complex that inhibits the activity of AP-2 transcription factors. Inactivation of these genes in neural crest cells (NCCs), from which the mesenchymal cells of the midline cranial sutures are derived, results in ACC. The data provide evidence that keratinocyte growth factors are secreted by these mesenchymal cells to promote the formation of the overlying epidermis. A key open question is now to understand the precise pathomechanisms that are downstream of this KCTD1/KCTD15 – AP-2 signaling axis, which Alexander and the team will explore in this proposal. These experiments are expected to provide exciting new insights into how skin formation is controlled, which likely has important clinical relevance for multiple skin diseases.

Memory ILC2s in atopic dermatitis

Grantee: Itziar Martinez Gonzalez, Assistant Professor, Karolinska Institutet, Sweden

Amount: DKK 3,753,750

Grant category: Research Grants in open competition

Year: 2025

Geography: Sweden

Atopic dermatitis (AD) is a common skin condition, characterized by itchy, inflamed skin. Identifying the allergens that trigger AD can be challenging, suggesting that allergen independent immune mechanisms are at play in AD. One key player in non-specific immune responses is a type of lymphocyte called ILC2. Itziar Martinez Gonzalez discovered that ILC2s in human skin can remember previous activations and induce a more severe inflammation upon subsequent triggers. Memory ILC2s could be important in triggering the recurrent flare-ups seen in AD. Now, Itziar Martinez Gonzalez aims to understand how memory ILC2s contribute to AD by studying how they are regulated at the cellular level and how they interact with their environment in the skin. Itziar and her team will also investigate if memory ILC2s play a role in the development of other allergic diseases associated with AD, like asthma. By studying how memory ILC2s function in AD, Itziar and the team hope to identify new ways to treat this chronic and often debilitating condition.

Uncovering the role of glutamine metabolism in host defense against bacterial skin infections

Grantee: Nathan Archer, Assistant Professor, Johns Hopkins School of Medicine, United States

Amount: DKK 3,957,833

Grant category: Research Grants in open competition

Year: 2025

Geography: USA

Staphylococcus aureus is the primary cause of skin infections and is a serious public health threat due to the emergence of antimicrobial-resistant strains as well as the failure of all vaccine clinical trials to date. Thus, there is an unmet need for new therapeutic strategies as alternatives to antibiotics and vaccines. Nathan Archer’s proposal aims to solve this problem by interrogating how our immune cells orchestrate protective responses against S. aureus infections. Specifically, Nathan and his team discovered that the amino acid, glutamine, is critical for host defense against S. aureus in the skin. They will use advanced “omics” approaches to understand how glutamine promotes host defense in specific immune cells in the skin using preclinical infection models as well as clinically infected skin. The goal of this study is to identify previously unrecognized immune pathways that can be targeted to augment host immunity against antimicrobial-resistant S. aureus and potentially other skin pathogens.

Systematic Profiling of Cytokine Responses for Targeted Treatment of Inflammatory Skin Diseases

Grantee: Thierry Nordmann, Dr. med. Dr. phil. nat. (MD/PhD), Max Planck Institute of Biochemistry, Germany

Amount: DKK 3,962,323

Grant category: Research Grants in open competition

Year: 2025

Geography: Germany

Chronic inflammatory skin diseases affect a quarter of the world’s population, but accurately diagnosing and effectively treating these conditions remains a challenge. This is largely because we do not fully understand how skin cells respond at the protein level to the numerous inflammatory signals. In Thierry Nordmann’s project, he and his team will create such a molecular dictionary using “omic technologies”, characterizing how skin cells react to a wide range of inflammatory signals (cytokines). Just as a language dictionary allows us to interpret the meaning of words, their molecular dictionary will enable us to understand the complex language of inflammation in diagnostic biopsies of the skin. In combination with artificial intelligence, they will use this dictionary to select the optimal therapy for the individual patient suffering from an inflammatory skin disease. This has the potential to improve patient outcomes while reducing side-effects and costs of ineffective therapies.

Dissecting the Role of Immunometabolism in CD4+ T Cell Skin Residency

Grantee: Tiffany Scharschmidt, Professor & Vice Chair of Research, The Regents of The University of California San Francisco, United States

Amount: DKK 3,416,251

Grant category: Research Grants in open competition

Year: 2025

Geography: USA

Tiffany Scharschmidts seek to understand how CD4+ T cells adapt to and survive in the skin. These cells are crucial for maintaining skin health but also drive diseases like atopic dermatitis and psoriasis. Despite this, we have much still to learn about the biology of CD4+ T cells residing in skin. To fill this gap, Tiffany and her team will use advanced single-cell techniques to study the metabolism of CD4+ T cells in both mouse and human skin. Preliminary data suggest these cells rely on glycolysis, and they aim to explore this further and identify other important metabolic pathways. In the first part of the study, they will use innovative mouse models and CRISPR-Cas9 technology to pinpoint key metabolic needs and regulators. In the second part, they will extend their findings to human skin, examining CD4+ T cells in both healthy and diseased states. The goal is to uncover how metabolism influences skin immune function, which could lead to new treatments for chronic inflammatory skin diseases.

Deciphering the coronin 1 pathway for selective inhibition of inflammatory skin diseases

Grantee: Jean Pieters, Principle Investigator, Biozentrum, University of Basel, Switzerland

Amount: DKK 3,989,627

Grant category: Research Grants in open competition

Year: 2025

Geography: Switzerland

Inflammatory skin diseases such as atopic dermatitis and psoriasis are debilitating and chronic conditions characterised by the appearance of rashes and scaly plaques. The symptoms are caused by overactivation of the immune system in which T cells play a key role. Current treatments are known to suppress the entire immune system or target pathways required for appropriate immunity and therefore are associated with significant risks for infections and cancer. Jean Pieters and his laboratory has recently defined a pathway that is selectively involved in T cell-mediated inflammatory skin disorders while being dispensable for normal immunity. Within this project Jean Pieters and his team aims to investigate the molecular mechanisms involved, and explore the potential of targeting this pathway as a therapeutic strategy for the suppression of skin inflammation while maintaining overall immunity. The results from this work may allow the delineation of hitherto unexplored and steroid-sparing therapies for inflammatory skin disorders.

Unraveling Skin Origins: Developing In Utero Gene Manipulation Tools to Decipher Ectoderm and Mesoderm Contributions to Skin Health and Disease

Grantee: Emma Andersson, Associate Professor, Karolinska Institutet, Sweden

Amount: DKK 3,990,001

Grant category: Research Grants in open competition

Year: 2025

Geography: Sweden

The versatile and complex functions of skin depend on its intricate structure, which comes from different cell origins during embryonic development. Despite its importance, we know little about how these origins shape skin health and disease across the body, partly because existing tools for studying skin are slow, expensive, and use many animals. Emma Andersson’s project aims to solve this by developing a fast and efficient way to study skin in different parts of the body, using a technique called in utero nano-injection, in mice. This method lets us precisely target and modify skin cells in developing mouse embryos, focusing on key regions like facial skin and body dermis. By creating new tools to study deeper cell layers in detail, Emma Andersson and her team can uncover how they work in normal conditions and diseases. This breakthrough would save time, reduce animal use, and open new doors for understanding and treating skin disorders.

Exploring Autoimmune Skin Diseases with Immune-Integrated 3D Skin Models

Grantee: Jonathan Brewer, Professor, University of Southern Denmark, Denmark

Amount: DKK 3,992,375

Grant category: Research Grants in open competition

Year: 2024

Geography: Denmark

Jonathan Brewer’s project, conducted in collaboration with Dr. Mike Barnkob, aims to advance skin biology by developing a much-needed human skin model with immune components, enabling detailed study of skin responses to stress and disease. By creating both normal and diseased skin models, with a focus on Cutaneous Lupus Erythematosus (CLE), Jonathan Brewer and his team will investigate the immune processes underlying CLE skin manifestations and provide a platform for developing targeted treatments. These models will also allow Jonathan and the team to study how skin and immune cells respond to UV radiation and mechanical forces, both of which play a significant role in CLE, where such stimuli can exacerbate skin lesions. A key innovation is the use of MERFISH technology, which maps gene activity within individual cells. This will reveal how specific genes are activated or suppressed in response to stimuli, providing insights into how skin adapts over time at the single-cell level. By comparing normal and CLE skin models, they will identify unique pathways involved in disease progression in CLE, offering potential targets for new therapeutic strategies.

The results of the project will be 3D skin models that mimic the structure and environment of human skin, enabling a wide range of experimental applications, including more rapid and ethical drug discovery. The project will also deliver the identification of pathways and molecular regulators involved in CLE and skin responses to UV and mechanical stimuli, supporting targeted treatment development and improved patient outcomes.

Wearable Sensor to Enhance Diagnostics and Health Equity in Allergic Contact Dermatitis

Grantee: Aydogan Ozcan, Professor, The Regents of the University of California, Los Angeles, USA

Amount: DKK 2,854,181

Grant category: Research Grants in open competition

Year: 2024

Geography: USA

Aydogan Ozcan’s project explores a potential alternative to the current diagnostic standard in allergic contact dermatitis (ACD) —patch testing —which has remained largely unchanged since its development over a century ago. It seeks to transform the diagnosis of ACD by developing a novel wearable sensor capable of remote monitoring and early detection. The sensor will be designed to measure changes in the skin’s optical properties, offering a more efficient, convenient, and comfortable alternative to the traditional method of patch testing. Aydogan Ozcan’s project includes the creation of skin phantom models’ representative of diverse skin tones to rigorously test the wearable sensor, followed by a phased human study.

The results of the project could enable more convenient, equitable, and cost-effective diagnosis in ACD, thereby improving patient outcomes. Additionally, this technology holds the potential to be adapted for the monitoring of other skin conditions, representing a significant advancement in the field of dermatology.

A new model for autoantibody formation in systemic sclerosis

Grantee: Rasmus Iversen, Postdoc, Oslo University Hospital, Norway

Amount: DKK 3,966,274

Grant category: Research Grants in open competition

Year: 2024

Geography: Norway

Rasmus Iversen’s project explores the hypothesis that complex formation between self- and non-self-antigen can drive pathogenic T cell-B cell interactions and autoantibody formation in autoimmune diseases like Systemic Sclerosis (SSc). Inspired by previous work on celiac disease, Rasmus Iversen and his team will use the function of the B-cell antigen as a starting point to decipher disease mechanisms. In SSc, the T-cell antigen(s) are unknown, but there is disease-specific production of autoantibodies to centromere proteins (CENPs) with CENP-B being a major B-cell antigen. To investigate autoantibody formation, Rasmus Iversen and the team will isolate CENP-B-specific B cells from blood of SSc patients. In the first step (WP1), they will characterize the cells’ phenotypes in detail. The cells will then be used for generation of recombinant CENP-B-specific monoclonal antibodies (mAbs) in WP2. These mAbs will be used for studying interactions between the immune system, CENP-B and target DNA. In WP3, they aim to identify DNA fragments of commensal bacteria that can form complexes with CENP-B and potentially drive T cell-B cell interactions.

The results of Rasmus Iversen’s project may provide Insight into disease mechanisms and can potentially lead to discovery of new therapeutic targets in e.g. systemic sclerosis (SSc), which is a serious autoimmune disease that affects the skin and internal organs.