“INFLEMT” MCSA fellowship

Project’s background | Inflammatory Bowel Diseases

Inflammatory Bowel diseases (or IBD) defines a group of chronic inflammatory disorders of the digestive tract. Its two major clinical manifestations are ulcerative colitis, which is mainly restricted to the colon, and Crohn’s disease, which can involve any segment of the gastrointestinal tract.

Compromised barrier functionality, chronic inflammation and persistent injury of the intestinal mucosa represent central drivers of the disease. This chronic tissue damage, with its recurring cycles of injury, repair attempts and persistent inflammation, triggers the development of intestinal fibrosis which is responsible for common complications requiring surgical intervention.

IBD represents a chronic idiopathic disease affecting 2.5 million people in Europe, with considerable costs for the health care system. The global rise of IBD prevalence together with the challenges associated with the development of complications and the unresponsiveness to biological therapies are posing an urgent need to better understand the mechanisms underpinning IBD pathogenesis.

Project goal | Understanding the role of the EMT Transition

Epithelial–to–Mesenchymal Transition (EMT) is a cellular trans-differentiation program activated during embryonic development and re-launched in pathological conditions such as fibrosis and cancer, by which epithelial cells lose their identity and acquire mesenchymal phenotypes and behavior. EMT has been implicated in the pathogenesis of IBD, although much of the knowledge was generated mainly through descriptive observations.

The objective of the INFLEMT project is to determine the functional consequences the activation of the EMT program has in terms of epithelial injury response and modulation of inflammation and fibrogenic response. In particular, the project aims to:

• profile EMT in human IBD to identify its cellular features and correlation with the disease stage;
• elucidate the impact of EMT on the integrity, functionality and regenerative capacity of the intestinal epithelial barrier;
• explore the effects of EMT on fibrosis development and modulation of the immune response to assess its role in sustaining the chronic intestinal disease.

The ultimate goal is to provide a novel understanding of the epithelial-driven mechanisms supporting persistent damage and inflammation, which could allow to design innovative approaches to protect the intestinal mucosa in IBD patients.