With the introduction of new CFTR modulators, people with cystic fibrosis (pwCF) have seen a significant improvement in their quality of life and life expectancy. However, with ageing, new health challenges and complications arise and these need to be addressed as early as possible.

There are reports describing a 3.5-fold increased cancer incidence in pwCF with most being gastrointestinal, namely colorectal cancer.

One of the main reasons lies in the mucosal lining of the intestine, made up of epithelial tissues that may already have suffered damage despite these new treatments. The CFTR protein plays a key role in maintaining healthy epithelial tissues: when it is defective, as in CF, epithelial cells lose their ability to function properly, becoming more prone to damage and less resilient to fully regenerate after challenges like microbial infections. This process, by which cells lose their normal epithelial structure and function and become more vulnerable, is called epithelial–mesenchymal transition (EMT).

In this project, the research team will study the mechanisms linking the CFTR defect to EMT using primary airway cells (provided by the FFC Ricerca Primary Culture Service) and intestinal organoids. The goal is to identify potential drug targets to improve and balance epithelial tissue regeneration, in order to improve the health and quality of life of pwCF.

This research will help identify new strategies to support tissue regeneration in pwCF, reducing complications and improving their condition as they age.