In Situ Gene Editing To Rescue Severe, Genetic Skin Diseases
Grantee: Sarah Hedtrich, Professor, University of British Columbia, Canada
Amount: DKK 4,191,726
Grant category: Research Grants
Year: 2025
Geography: Canada
Some rare skin conditions, like Epidermolytic Ichthyosis (EI) and Harlequin Ichthyosis (HI), are caused by changes in certain genes. These diseases can be severe and often have no effective treatments, making life very hard for patients. Gene editing—a powerful new technology—could fix these faulty genes and provide lasting cures, but delivering these tools into the skin and targeting the right cells is a major challenge. This project aims to develop new, skin-applied gene-editing treatments. The goals are to: (1) create ways to correct the gene changes that cause EI and HI, (2) design messenger RNA (mRNA) molecules that work well in skin cells, and (3) make tiny delivery packages, called lipid nanoparticles (LNPs), that carry the tools to skin stem cells. By improving mRNA design and targeting, the approach could lead to long-lasting, possibly permanent treatments for severe genetic skin diseases.
Identification of shared T-cell pathways in the pathogenesis of atopic dermatitis and inflammatory bowel disease
Grantee: Francesca Capon, Leadership Chair in Genetic Medicine, University of British Columbia
Amount: DKK 2,116,583
Grant category: Serendipity Grants
Year: 2025
Geography: Canada
Francesca Capon unexpectedly discovered that deleterious TCF3 mutations cause a severe form of atopic dermatitis (AD) associated with inflammatory bowel disease (IBD). By querying large-scale genetic repositories, the project also observed that common TCF3 alleles are associated with susceptibility to AD and IBD in the general population. TCF3 encodes a transcription factor that plays a key role in T cell differentiation. Thus, the project hypothesizes that TCF3 mutations cause abnormal T cell activation, leading to skin and gut inflammation. Given severe AD is a risk factor for IBD, it is further proposed that the study of TCF3 mutations will shed new light on mechanisms that may underpin both conditions.
The aim of the study is to validate the involvement of TCF3 in the pathogenesis of AD and IBD. This will be achieved by identifying the immune pathways that are altered by TCF3 dysfunction in skin and gut. The plan integrates:
i) in-vitro studies to determine the impact of TCF3 mutations on protein function
ii) immune phenotyping of T cells from individuals harbouring TCF3 mutations
iii) in-silico analyses to define transcriptional networks driven by TCF3
The project expects to identify TCF3-dependent pathways contributing to AD and IBD pathogenesis. This will shed new light on shared disease mechanisms with potential to inform targeted treatment of individuals affected by both conditions.