Grant category: Research Grants in open competition

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.

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.

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.

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.

Grant category: Research Grants in open competition

Year: 2024

Geography: Japan

Kenji Kabashima’s project explores the hypothesis that skin possesses the capacity for independently initiating acquired immune responses. More specifically, it aims to investigate the hypothesis that “skin functions as a site for induction of diverse immune responses” by leveraging the inducible skin-associated lymphoid tissue (iSALT) previously discovered by Kenja Kabashima and his team. The objectives are to establish a novel method for local immune manipulation utilizing iSALT and to elucidate the mechanisms underlying the induction of various immune responses within the local skin environment. To achieve these goals, an innovative approach is proposed: combining verification of iSALT existence in human skin, functional characterization of iSALT, application of 3D bioprinter technology, development of human skin organoids, implementation of cutting-edge skin imaging techniques, and utilization of multi-omics analyses. The expected outcomes include elucidation of molecular mechanisms governing immune regulation in local skin areas, potential applications in treating immunological and inflammatory skin diseases, and insights into managing skin malignancies.

The results of Kenji Kabashima’s research have the potential to significantly advance our understanding of skin immunology and open new avenues for therapeutic interventions in dermatological conditions.

Grant category: Research Grants in open competition

Year: 2024

Geography: USA

Maria Teves’ project explores mechanisms behind formation of dermal fibrosis, which is a hallmark of several skin disorders, including systemic sclerosis (SSc). Despite the identification of various contributing factors, the precise molecular mechanisms underlying skin fibrosis in SSc remain poorly understood and there is no effective treatment. In order to uncover these mechanisms and develop new therapeutic strategies, the project focuses on primary cilia (PC), which are specialized solitary cellular organelles involved in molecular signaling. Recently, Maria Teves and her research group discovered links between altered PC to SSc pathophysiology, revealing significant alterations in PC and PC-associated gene expression in skin biopsies from SSc patients. Furthermore, it was found that profibrotic signaling can be triggered both in vivo and in vitro by the genetic ablation of PC-associated genes or by pharmacological agents that damage PC. Building on this critical evidence, the project will test the hypothesis that PC represent novel therapeutic targets for SSc skin fibrosis. A comprehensive approach is proposed to define molecular contributions of PC to the pathogenesis of skin fibrosis and assess the potential of PC-targeted therapies for mitigating fibrotic phenotypes.

Maria Teves’ experiments may lay the groundwork for advanced understanding and possibly treatment and future clinical advances for people suffering from fibrotic skin conditions.

Grant category: Research Grants in open competition

Year: 2024

Geography: USA

Anand Ganesan’s project explores the activation of the innate immune system in rosacea, a chronic skin condition which affects 5% of the world’s population. Rosacea skin has an increased number of blood vessels, which can be induced by the naturally occurring anti-microbial peptide cathelicidin, which is produced by keratinocytes in rosacea skin. While treatment targets and new pharmacotherapies for rosacea have been identified, this knowledge has not yet been translated into new rosacea therapies. RhoJ, a member of the CDC42 GTPase family, plays a critical role in angiogenesis (formation of new blood vessels) in skin and other organs, and RhoJ knockout mice have decreased number of blood vessels in the skin as compared to wild type animals. Anand Ganesan and the research group has discovered a new class of small molecules that inhibit CDC42 GTPase signaling, which prevents vessel accumulation in the skin and colon through a RhoJ-dependent mechanism and also blocks the vascularization of human organoids. Anand Ganesan’s project couples’ single cell and spatial transcriptomics approaches (i.e., analyses of how genes are expressed in individual cells as well as throughout a tissue) with advanced bioinformatics to identify vessel inducing signals in tissue. The research plan includes 1) coupling single cell and spatial transcriptomics with advanced bioinformatics to identify rosacea inducing signals; 2) quantifying vascular changes in rosacea in mice and human model systems; and 3) testing the efficacy of CDC42 inhibitors at blocking cathelicidin-induced angiogenesis.

The project aims to identify new drug targets and test the efficacy of new treatments for rosacea.

Grant category: Research Grants in open competition

Year: 2024

Geography: USA

Tamia Harris-Tryon’s study explores atopic dermatitis (AD) which affects seven percent of adults and twenty percent of children. AD has the highest impact on patient quality of life among skin disorders. The pathogenesis of AD is incompletely understood, and there is an increasing appreciation for the contributions of the microbiome. During AD flares, Staphylococcus aureus expands and exacerbates inflammatory responses and skin damage. While S. aureus dominates the skin microbiome in AD, the mechanisms that drive bacterial expansion during inflammation remain unclear. This question is important because skin breakdown in AD is aggravated by S. aureus toxins. S. aureus exotoxins have been shown to stimulate skin inflammation. Tamia Harris-Tryon’s project will test the central hypothesis that testosterone promotes S. aureus-induced skin damage and inflammation in AD as well as investigate how testosterone stimulates S. aureus-induced skin damage in culture and in mouse models. These experiments will also make use of genetically engineered mice with reduced testosterone production in the skin. This approach will reliably determine how testosterone regulates S. aureus-induced skin damage and inflammation.

The results of Tamia Harris-Tryon’s project may reliably determine how testosterone regulates S. aureus-induced skin damage and inflammation.

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.

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.