Grant geography: USA

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: 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.

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.

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.

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.

Grant category: Serendipity Grants

Year: 2024

Geography: USA

Nathan Archer’s project investigates the surprising finding that dermal adipocytes and their crosstalk with eosinophils may play an important role in the development of atopic dermatitis.

The aim of Nathan Archer’s original project was to investigate the role of eosinophils, a type of immune cell, in the pronounced bacterial dysbiosis seen in relation to atopic dermatitis (AD). During those studies, Nathan Archer and his team serendipitously discovered an unexpected interaction of adipocytes with eosinophils in the skin, which was also associated with skin inflammation. This novel link will be investigated in Nathan’s project.

Grant category: Standalone grants

Year: 2024

Geography: USA

This interdisciplinary event will convene leading experts in the field of science of science and innovation, aiming to provide a multi-channel platform that brings together both producers (scientists from industry and academia) and consumers (policymakers, publishers, funders, administrators, etc.) of the field.

Read more

Grant category: Research Networking

Year: 2024

Geography: USA

The goal of the 71st Annual Montagna Symposium, Skin of Color Dermatology: The Interaction of Science & Society, is to promote practicing clinicians, residents, trainees, basic and translational researchers who are underrepresented in science and medicine, assembling leading scientists and clinicians engaged in research and treatment of diseases that disproportionately affect skin of color to share knowledge and foster collaborations.

The event will take place on 17-21 October 2024 in Washington, USA and aim to enable interaction between new and established scientists and dermatologists who work collectively to advance the field of skin research. The format will include short talks organized in sessions by topic, with time for questions and discussion. Young investigators get the opportunity to interact with experienced researchers and clinicians in their fields both formally and informally throughout the meeting, and the meeting provides participants with a springboard for new research activities or clinical practices.

Read more.

Grant category: Research Grants in open competition

Year: 2024

Geography: USA

Xiaoyang Wu’s project aims to engineer self-amplifying RNA vector as a platform for gene therapy of recessive X-linked ichthyosis, with potential for treatment of other skin diseases.

Skin ichthyoses are a group of heterogeneous genetic diseases that are characterized by hyperkeratosis, localized or generalized scaling, and often associated with xerosis, hypohidrosis, erythroderma, and recurrent infections. So far, mutations in more than 50 genes have been shown to cause ichthyosis, which affect a variety of different cellular processes, ranging from DNA repair, lipid biosynthesis, cell adhesion, and skin differentiation. Recessive X-linked ichthyosis (RXLI) is the second most common form of inherited ichthyosis. RXLI is caused by mutations in the STS gene on the X chromosome, which encodes microsomal steroid sulfatase. The skin abnormalities of RXLI are caused by the impact of excess cholesterol sulfate, which affects lipid synthesis, organization of the lamellar lipids that provides the skin permeability barrier, corneodesmosome proteolysis, and epidermal differentiation.

As a genetic disorder, RXLI is a life-long condition that can significantly affect domestic life and cause psychological problems for the patients. More effective treatment beyond current symptomatic management is urgently needed. Xiaoyang Wu’s project will explore the possibility that engineered self-amplifying RNA vector can serve as a novel platform for gene therapy of RXLI.

Xiaoyang Wu’s project may serve as proof-of-concept for a novel paradigm for the treatment of patients with genetic skin disorders.

Grant category: Research Grants in open competition

Year: 2024

Geography: USA

Jeffrey Rasmussen’s project investigates the mechanisms governing Langerhans cells’ immune response in wound healing, particularly the role of the microtubule cytoskeleton.

Skin provides a robust and durable physical barrier essential for regulating hydration and repelling pathogens. Damage to skin must be rapidly resolved to maintain organ homeostasis. Epidermal-resident immune cells known as Langerhans cells use dendritic protrusions to dynamically surveil the skin microenvironment, which contains epithelial keratinocytes and somatosensory peripheral axons.

The mechanisms governing Langerhans cell dendrite dynamics and responses to tissue damage are not well understood. Jeffrey Rasmussen and his lab have developed a tractable system using adult zebrafish to study Langerhans cell dynamics. Initial studies using this system revealed several new discoveries, including: 1) that Langerhans cells are the primary phagocyte for degenerating somatosensory axons; 2) Langerhans cells undergo stereotyped responses to local and tissue-scale keratinocyte wounds; and 3) the actin regulator ROCK regulates key aspects of Langerhans cell wound responses. Despite advances in identifying mechanisms of actin function in Langerhans cells, roles for the microtubule cytoskeleton in Langerhans cell biology remain essentially unknown. In preliminary studies, Jeffrey Rasmussen has developed a novel transgenic reporter for microtubules in Langerhans cells and found that the microtubule cytoskeleton dynamically reorganizes during wound responses. His project aims to determine how the microtubule cytoskeleton contributes to the intracellular trafficking and dynamic wound responses of Langerhans cells.

The results of Jeffrey Rasmussen’s project could lead to new fundamental understandings of Langerhans cell biology and dynamics.