Completed Lungs & Breathing Digestion, Kidneys & Other Organs

Defining ‘clinically actionable’ genetic mechanisms in atopic eczema risk and resolution

Funder Wellcome Charity-funded
Recipient organisation University of Edinburgh
Funding £2.3M
Period Nov 2020 — Oct 2025

In plain English

AI plain-English summary

A single genetic change can triple a child’s risk of eczema, and scientists now want to understand why some children grow out of it while others do not. Eczema affects millions of people, causing itchy, inflamed skin that can lead to chronic discomfort and infections. Although the condition is highly heritable, the biological pathways that drive it—and those that allow some cases to resolve—remain poorly understood. This project focuses on two major genetic risk regions: one containing the FLG gene, which produces a key skin-barrier protein, and another near the EMSY gene, which the team has shown controls how skin cells build that barrier. The researchers will also test how three common environmental factors—tobacco smoke, washing products, and pet allergens—interact with these genes, using skin organoids grown in the lab. They will validate their findings in a long-running birth cohort of over 25,000 people. If successful, this work could identify molecular targets for drugs that push eczema into long-term remission, rather than just managing symptoms. It could also inform prevention strategies, such as advising families with specific genetic profiles to avoid certain triggers. The research is primarily fundamental science, but understanding gene-environment interactions at this level has previously led to breakthroughs in allergy treatments and personalised medicine.

View original technical description
Atopic eczema is an itchy condition characterised by skin barrier dysfunction and inflammation. It frequently causes chronic morbidity, but a subset of cases enter long-term remission, demonstrating that resolution may be a tractable therapeutic aim. Eczema is highly heritable. mutations in FLG are the strongest genetic risk and a locus on chr11q13.5, for which the nearest gene is EMSY, has a multiplicative effect. We have shown that EMSY is a transcriptional regulator in skin, controlling multiple aspect of barrier formation. We will investigate molecular mechanisms at these two major risk loci: chr1q21.3 (FLG, FLG-AS1 and related genes) and chr11q13.5 (EMSY and LRRC32), aiming to define pathways contributing to eczema resolution. Findings will be tested in a well-characterised birth cohort (ALSPAC), to confirm clinical relevance. Analyses of European cohorts (n>25,000) show evidence of gene-environment interactions in eczema, but these findings require validation. We will use an optimised skin organoid model to investigate three environmental factors (tobacco smoke, wash-products and pet allergens) for which there is evidence of interaction with FLG genotype. Detailed functional and biochemical phenotyping will increase understanding of gene-environment interactions. This work will inform eczema prevention strategies and characterise mechanisms contributing to eczema resolution, as future therapeutic targets.

View the original record at the funder ↗

Researchers

Sara Brown (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Molecular mechanisms in atopic skin.
Understanding the Regulation of Epidermal Differentiation Genes by Filaggrin in Eczema
The Genetic Epidemiology of Atopic Dermatitis
The role of CD1a-restricted T cells in the pathogenesis of atopic eczema
Exploiting growth factor modulation of alarmin release in atopic dermatitis

Original classification

Senior Research Fellowship Renewal

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