The 2025 Gordon Research Conference on Epithelial Differentiation and Keratinization (GRC-EDK)

Grantee: Associate Professor Maria Kasper, Karolinska Institutet, SE on behalf of Gordon Research Conferences, USA

Amount: DKK 319,712

Grant category: Research Networking

Year: 2024

Geography: USA

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.

Primary cilia: a novel target for skin fibrosis

Grantee: Maria Teves, Assistant Professor, Virginia Commonwealth University, USA

Amount: DKK 3,914,945

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.

Identifying new, molecularly-targeted treatments for rosacea

Grantee: Anand Ganesan, Professor, The Regents of the University of California Irvine, USA

Amount: DKK 4,000,000

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.

Determining the Impacts of Testosterone on S. aureus-induced skin Damage in Atopic Dermatitis

Grantee: Tamia Harris-Tryon, Associate Professor, UT Southwestern Medical Center, USA

Amount: DKK 2,852,706

Grant category: Research Grants in open competition

Year: 2024

Geography: USA

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

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.

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.

How innervation regulates regeneration and scarring responses

Grantee: Ya-Chieh Hsu, Professor, Harvard University

Amount: DKK 4,000,000

Grant category: Serendipity Grants

Year: 2024

Geography: USA

Ya-Chieh Hsu’s project investigates the mechanisms behind the unexpected observation that wound healing slows upon increased innervation of the surrounding tissue.

During testing of a virus-based tool designed to genetically manipulate skin cells Ya-Chieh Hsu and her team serendipitously discovered that increased innervation at a wound site slows healing and leads to increased scarring. This discovery suggests that wound-induced hyper-innervation may be important in driving scarring and fibrosis.

Dissecting the effects of sex hormones and sex chromosomes in heightened cutaneous inflammation in female mice

Grantee: Philip Scumpia, Associate Professor, The Regents of the University of California, Los Angeles

Amount: DKK 3,977,971

Grant category: Serendipity Grants

Year: 2024

Geography: USA

Philip Scumpia’s project will investigate a surprising discovery that links gender to differences in immune responses.

Philip Scumpia and his team created new formulations of biomaterials intended to improve cutaneous wound healing and decrease size of scars in his current LEO Foundation-funded project. While evaluating the immunological mechanisms, Philip and his team observed considerable variability in immune cell recruitment to the different hydrogels. After careful scrutiny they realized this variability was entirely due to the fact that female mice developed stronger immune responses to the hydrogel than male mice. Strikingly, female mice displayed a much earlier and more severe skin inflammation in other mouse models studied in the laboratory includingeczema, psoriasis, and sunburn.