From Flexibility to Dysfunction: The Impact of Oxidative Stress on the Structural Integrity of Skin Elastin
Grantee: Andrea Heinz, Associate Professor, LEO Foundation Center for Cutaneous Drug Delivery, University of Copenhagen, Denmark
Amount: DKK 3,987,617
Grant category: Research Grants in open competition
Year: 2025
Geography: Denmark
Elastin is a structural protein essential for human life. It provides the elasticity needed for organs like skin, lungs, and blood vessels, allowing your skin to stretch, your lungs to expand for breathing and your blood to flow smoothly. As we age, factors like oxidative stress can make elastin stiffer, reducing the skin’s elasticity and accelerating the aging process. This can lead to skin conditions, such as thickening and furrowing or increased fragility. This project uses advanced analytical techniques to investigate how oxidative damage affect elastin’s structure and stability, starting with its building block, tropoelastin, and extending to skin elastin. Our goal is to understand how these alterations contribute to elastic fiber breakdown and tissue dysfunction. Ultimately, this knowledge will help us understand how elastin damage drives disease and tissue degeneration, which could lead to better treatments that protect tissue elasticity and improve overall health.
SERS-Enabled Wound-Sampling Patches for Rapid Infection Monitoring
Grantee: Gohar Soufi, Postdoc, Technical University of Denmark, Denmark
Amount: DKK 3,999,657
Grant category: Research Grants in open competition
Year: 2025
Geography: Denmark
Millions of people suffer from infected wounds each year, which can lead to serious complications or even death if untreated. Current methods for diagnosing wound infections are slow and require specialized laboratories. Our project aims to create a simple, portable device that uses advanced materials to detect infections quickly and accurately right at the patient’s bedside. This technology could revolutionize how infections are diagnosed, helping doctors start treatments sooner and improving patient outcomes.
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.
ATHENA- Artificial Intelligence Towards Holistic Evaluation of Skin Nanotexture Alterations
Grantee: Edwin En-Te Hwu, Associate Professor, Technical University of Denmark, Denmark
Amount: DKK 3,992,314
Grant category: Research Grants in open competition
Year: 2024
Geography: Denmark
The ATHENA project will explore the untapped potential of stratum corneum nanotexture (SCN, the nanoscale morphology of the outermost skin layer) to advance research and clinical evaluations of challenging-to-diagnose conditions: psoriasis, hand eczema (HE), and actinic keratosis (AK). Edwin En-Te Hwu’s MIDAS group has previously demonstrated that deep learning models could classify atopic dermatitis severity through SCN with high accuracy. Building on these findings, ATHENA aims to identify disease phenotypes across ethnicities and skin phototypes to optimize treatment strategies. ATHENA will: a) collect 1,050 stratum corneum tape strip samples from five countries across four continents, b) build a large dataset of 13,500 SCN images, c) develop self-supervised deep learning models to correlate SCN with skin conditions, and d) explore and identify robust SCN biomarkers for skin diseases. The non-invasive stratum corneum tape strip sampling method is painless and repeatable, causing no tissue damage and allowing frequent monitoring of therapy and disease progression. This method enables patients to collect samples at home for remote analysis, facilitating early detection and intervention to reduce social and economic burden.
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.
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.
Epidemiology and genetics of rosacea and co-morbidities
Grantee: Ole Pedersen, Chief physician, Professor, Zealand University Hospital, Køge
Amount: DKK 2,715,598
Grant category: Research Grants in open competition
Year: 2024
Geography: Denmark
Ole Pedersen’s project aims to determine the genetic basis of rosacea and the causal connection between rosacea and its comorbidities.
Rosacea is a common chronic inflammatory skin disease of the face, which may manifest as a bulbous nose, central erythema, flushing, inflammatory papules/pustules, or broken vessels in addition to diverse eye involvement. Severe rosacea has a large impact on the patients’ quality of life, social and psychological well-being and has been linked to many systemic comorbidities including cardiovascular, psychiatric, neurological, and cancer diseases.
Ole Pedersen’s project aims to identify the genetic pathways of rosacea and determine the causal connection and modifiable risk factors to previously reported systemic comorbidities. He has recently developed a rosacea classification tool and applied it to a deep phenotyped cohort of ~55,000 Danes allowing for detailed analysis of association between rosacea, risk factors and co-morbidities. In addition, Ole Pedersen has facilitated genotyping of 500,000 Danes that can be used for genome wide association study meta-analysis with other genetic cohorts from Iceland, Finland, UK and USA to perform the so far largest genetic study on rosacea. Based on this analysis, his project will determine the genetic correlations and perform Mendelian randomization analysis of the causation between rosacea and comorbidities.
Ole Pedersen’s project may provide new understanding of disease pathogenesis and the link to systemic comorbidities, paving the way for developing new treatments and early targeted interventions.
Structural dissection and dynamic insights into the molecular switch of mast cells and basophils: a blueprint for novel urticaria therapies
Grantee: Rosaria Gandini, Assistant Professor, Aarhus University
Amount: DKK 3,462,144
Grant category: Research Grants in open competition
Year: 2024
Geography: Denmark
Rosaria Gandini’s project investigates the molecular details of the IgE-FceRI complex and its functioning on mast cells and basophils in order to improve treatment opportunities for urticaria.
Urticaria, a common inflammatory skin disorder characterized by itchy wheals, angioedema, or both, manifests in acute (AU) and chronic (CU) forms. It significantly impairs patients’ quality of life, causing sleep disturbances due to pruritus, fatigue, and anxiety. The symptoms arise from the activation of skin mast cells and basophils, leading to the release of histamine and other inflammatory mediators. This activation is initiated by cross-linking and clustering of the complexes between immunoglobulin E (IgE) and its high-affinity receptor, FceRI, which is expressed on the surface of these cells.
The FceRI-IgE complex hence acts as a powerful molecular switch, which initiates the inflammatory cascade and thus provides an attractive target for drug intervention. The structural basis of this activity, however, remains open.
Rosaria Gandini’s project aims to determine the structure of the FceRI-IgE membrane complex using state of the art Cryo Electron Microscopy (cryo-EM).
Successful elucidation of the molecular details of the entire complex and its conformations will allow identification of specific regions on FceRI for targeted intervention. This knowledge will deepen the understanding of the interaction of antibodies with Fc receptors in general and may pave the way for the development of specific and effective treatment of urticaria and related disorders.
Protein stability and misfolding in keratin disorders
Grantee: Rasmus Hartmann-Petersen, Professor, University of Copenhagen
Amount: DKK 2,600,678
Grant category: Research Grants in open competition
Year: 2024
Geography: Denmark
Rasmus Hartmann-Petersen’s project aims to characterize all possible missense variants (changes in genes which introduce a different amino acid in the resulting protein) in human keratins and investigate the importance of these variants in associated diseases.
Keratins are intermediate filament proteins that form a cytoskeletal network within cells. They are expressed in a tissue-specific fashion and form heterodimers, which then further oligomerize into filaments. Variants in several keratin encoding genes are linked to a range of hereditary disorders, including several epidermal skin diseases. On the molecular level, some pathogenic keratin variants appear to cause aggregation of the keratins.
In Rasmus Hartmann-Petersen’s project it is hypothesized that most keratin-disorders are protein misfolding diseases, i.e. diseases where the underlying genetic variants cause misfolding of the encoding protein. Rasmus and his team aim to explore this hypothesis by using computational tools, including large language models (a specific form of AI). They will test the validity of the computational predictions through focused cellular studies on selected keratins and identify components regulating keratin turnover.
The results will highlight the underlying molecular mechanisms for keratin-linked human disorders and provide predictions on the severity of all possible (both known and yet unobserved) coding variants in human keratin genes. The results could be of diagnostic value, but may also highlight the cellular protein folding and protein quality control machinery as potential therapeutic targets.
Architecture of the Herpes simplex replication machinery and its inhibitors
Grantee: Eva Kummer, Associate Professor, Copenhagen University
Amount: DKK 4,902,307
Grant category: Research Grants in open competition
Year: 2024
Geography: Denmark
Eva Kummer’s project targets to improve our understanding of the replication machinery of the skin-infecting herpes simplex virus (HSV) in order to improve and expand treatment opportunities.
HSV is one of the most widespread viral infections. The virus persists lifelong in the nerve system of the host and causes recurrent infections with mild to severe symptoms.
Since decades, treatment of herpes infections has exclusively targeted the viral replicative DNA polymerase (an enzyme that copies the viral DNA) using nucleoside analogs. However, resistance to current nucleoside analogs is emerging necessitating the search for alternative targets.
A major caveat in developing anti-herpetic compounds is a lack of structural information of other components of the herpes simplex replication system, which are likely strong candidates for targeted drug development. Eva Kummer and her team will use cryo-electron microscopy to visualize the architecture and working principles of the protein complexes that drive herpes simplex replication. They will also aim to clarify how novel anti-herpetic drugs block the viral replication machinery and why naturally occurring resistance mutations inhibit their action.
Overall, the project will generate structural and functional insights of the HSV replication strategy and potentially improve and accelerate anti-viral drug design.