Explore our grantees and awardees

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

Grant category: Research Grants in open competition

Year: 2024

Geography: USA

Grant category: Research Grants in open competition

Year: 2024

Geography: Denmark

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: 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.

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: Research Grants in open competition

Year: 2024

Geography: United Kingdom

Clare Bennett’s project explores the skin’s sensory nerves. These protect us from harm, such as heat or toxins, yet little is known about how they are sustained. Psoriasis is a common disfiguring skin condition, where pain suffered by patients and its impact on mental health and quality of life are frequently overlooked. Understanding how sensory nerves are protected in healthy skin could reveal why this process fails in psoriasis, leading to pain. Langerhans cells (LCs), immune cells in the skin’s epidermis, are known for detecting infections. However, emerging evidence suggests that LCs may also perform non-immune roles that have not been thoroughly studied. This project aims to investigate how psoriasis changes the way LCs interact with the nerves in the skin. Clare Bennett and her team hypothesize that changes in psoriatic skin disrupt protective function, leading to uncontrolled nerve growth. Clare Bennett and her team combine expertise in immunology, neuroscience, and dermatology. They will use advanced microscopy, genetic models, and gene expression analysis in well-established lab models to study LC-nerve interactions and aim to validate their findings using psoriasis patient skin samples. The results of Clare Bennett’s project could fill critical gaps in our understanding of sensory nerve regulation. Ultimately, the hope is to uncover new strategies to reduce pain and improve quality of life for psoriasis patients and potentially those with other skin diseases.

Grant category: Research Grants in open competition

Year: 2024

Geography: United Kingdom