“INFLEMT” MCSA fellowship
Principal Investigator: Sara Lovisa
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.
Sara Lovisa is a junior group leader at Humanitas Research Hospital, where she leads the Plasticity, Fibrosis and Cancer Lab. In 2021 she was awarded a Marie Sklodowska-Curie Action fellowship from the Horizon 2020 framework program of the European Union and a Start-Up Grant from the Italian Association for Cancer Research (AIRC) thanks to which she set up her own laboratory in Humanitas, after many years of research at the University of Texas MD Anderson Cancer Center di Houston, USA.
Rizzo G, Pineda Chavez SE, Vandenkoornhuyse E, Cárdenas Rincón CL, Cento V, Garlatti V, Wozny M, Sammarco G, Di Claudio A, Meanti L, Elangovan S, Romano A, Roda G, Loy L, Dal Buono A, Gabbiadini R, Lovisa S, Rusconi R, Repici A, Armuzzi A, Vetrano S. Pomegranate Extract Affects Gut Biofilm Forming Bacteria and Promotes Intestinal Mucosal Healing Regulating the Crosstalk between Epithelial Cells and Intestinal Fibroblasts. Nutrients. 2023 Apr 5;15(7):1771. doi: 10.3390/nu15071771. PMID: 37049615; PMCID: PMC10097402.
Rizzo G, Rubbino F, Elangovan S, Sammarco G, Lovisa S, Restelli S, Pineda Chavez SE, Massimino L, Lamparelli L, Paulis M, Maroli A, Roda G, Shalaby M, Carvello M, Foppa C, Drummond SP, Spaggiari P, Ungaro F, Spinelli A, Malesci A, Repici A, Day AJ, Armuzzi A, Danese S, Vetrano S. Dysfunctional Extracellular Matrix Remodeling Supports Perianal Fistulizing Crohn’s Disease by a Mechanoregulated Activation of the Epithelial-to-Mesenchymal Transition. Cell Mol Gastroenterol Hepatol. 2023;15(3):741-764. doi: 10.1016/j.jcmgh.2022.12.006. Epub 2022 Dec 12. PMID: 36521659; PMCID: PMC9898761.
Garlatti V, Lovisa S, Danese S, Vetrano S. The Multiple Faces of Integrin-ECM Interactions in Inflammatory Bowel Disease. Int J Mol Sci. 2021 Sep 28;22(19):10439. doi: 10.3390/ijms221910439. PMID: 34638778; PMCID: PMC8508809.
Lovisa S. Epithelial-to-Mesenchymal Transition in Fibrosis: Concepts and Targeting Strategies. Front Pharmacol. 2021 Sep 7;12:737570. doi: 10.3389/fphar.2021.737570. PMID: 34557100; PMCID: PMC8454779.