Project description
Novel insight into the pathogenesis of chronic intestinal inflammation
Epithelial–mesenchymal transition (EMT) is a process where immotile epithelial cells convert into migrating mesenchymal cells, and it plays a central role during development. However, EMT becomes reactivated in certain disorders such as cancer, contributing to malignant transformation, progression and resistance to therapy. The EU-funded INFLEMT project focuses on the role of EMT in inflammatory bowel disease (IBD), a chronic disorder of the digestive tract. Researchers will study EMT in IBD and elucidate its impact on intestinal epithelial cells and on fibrosis development. Considering the high prevalence of IBD, results will disclose important information on disease pathogenesis and may lead to new treatment strategies.
Objective
Inflammatory bowel disease (IBD) defines a group of chronic inflammatory disorders of the digestive tract, with ulcerative colitis and Crohn’s disease being its two major clinical manifestations, affecting 2.5 million people in Europe. The high prevalence of IBD in Europe and the multiple clinical challenges associated with a significant degree of unresponsiveness to anti-inflammatory therapies and development of complications requiring surgical intervention demand a deeper understanding of the cellular and molecular mechanisms underpinning IBD.
This project aims to understand the role of the process termed Epithelial–to–Mesenchymal Transition (EMT), an embryonic cellular trans-differentiation program re-launched in many pathological conditions, in the pathogenesis of IBD. EMT has in fact been detected in the inflamed intestinal mucosa and surrounding fibrotic areas of IBD patients and experimental models of colitis, however whether EMT functionally contributes to the pathogenesis of IBD is poorly understood.
The INFLEMT project aims to: 1) profile EMT in human IBD to identify its cellular features and correlation with the disease stage; 2) elucidate the impact of EMT on the integrity, functionality and regenerative capacity of the intestinal epithelial barrier; 3) explore the effects of EMT on fibrosis development and modulation of the immune response to assess its role in sustaining the chronic intestinal disease.
These objectives will be pursued by utilizing patient-derived biopsies as well as novel mouse models to manipulate EMT in the intestinal epithelium. Comprehensive analysis, including RNA-sequencing and multispectral imaging, of the involved cellular and microenvironmental components (epithelial barrier, immune cells, fibroblasts) will be performed in acute and chronic colitis settings to mechanistically configure EMT as an epithelial injury response and a major functional driver in the pathogenesis of IBD.
Fields of science
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
20090 Pieve Emanuele
Italy