Silvio Danese View More
- AddressVia Rita Levi Montalcini 4 Pieve Emanuele
Prof. Danese and his lab have been devoted to the investigation of new potential mechanisms involved in Inflammatory Bowel Disease (IBD) pathogenesis, with particular interest in the pathogenic role of non-immune cells (i.e. epithelial cells, endothelial cells and fibroblasts) as key players in the chronic inflammatory processes. The lab has explored the functional role of vascular biology in the gut unveiling: i) the augmented pathological lymphangiogenesis in the inflamed mucosa of IBD patients, ii) the link between coagulation and vascular homeostasis in triggering intestinal inflammation, iii) the role of epithelial and endothelial junctional molecules in controlling intestinal epithelial barrier integrity and iv) the recruitment of inflammatory immune cells. Other studies have allowed for the identification of new molecular mechanisms mediating the anti-inflammatory effects of MSCs in resolving intestinal inflammation. More recently, the interest of the lab has moved towards exploring the complex interplay between environmental factors and non-immune cells in IBD-related complications including colorectal cancer and intestinal fibrosis.
Our activities are focused on elucidating the molecular basis of intestinal inflammation in IBD and IBD-related complications, according to different aspects:
Pro-resolving lipid mediators as a new approach to therapy in IBD
For many years, dysregulations in pro-inflammatory pathways have been considered at the basis of IBD pathogenesis. Nevertheless, anti-inflammatory treatments do not always lead to remission. New evidences indicate that defects in pro-resolving pathways might also underlie the pathogenesis of this disease. We recently discovered that IBD patients display a defect in the production of pro-resolving lipid mediators which leads to chronic intestinal inflammation.
The gut virome
Alterations in the gut microbiota composition are well-recognized contributors to the pathogenesis of IBD. Bacteria, fungi, archaea, and viruses, all populating the human intestine, were found to control gut homeostasis, with a continuous pathogen-host interplay which impacts the health of the entire organism. In particular, our laboratory is currently investigating whether viruses oversee the initial phases of IBD and if so which ones do so. We recently found that a specific eukaryotic viral signature characterizes UC and CD-derived intestinal samples in the early stage of inflammation. We are now actively investigating how these viral entities may affect intestinal homeostasis, eventually pointing out novel molecular mechanisms underlying IBD etiopathogenesis.
Fibrotic process: a complication of intestinal inflammation
Intestinal fibrosis is a common and serious complication experienced by many Crohn’s Disease patients with no specific treatments.
Multiple factors have been considered to be involved in CD-associated intestinal fibrosis, including cellular and molecular profibrogenic factors, extracellular matrix molecules, and the matrix metalloproteinase/ tissue inhibitor of metalloproteinase system. However, so far, the relative contribution of each component in the pathogenesis remains unclear. Our studies are aimed at understanding the molecular pathways underlying fibroblast activation in inducing intestinal fibrosis and the effects of environmental factors, including diet, in this process.
Patients suffering from IBD have an increased risk of developing colitis-associated cancer (CAC). Severity, extent of disease and the duration of inflammation seem to be major risk factors associated with the development of CAC in these patients. Our studies are aimed at exploring the molecular mechanisms sustaining the link between inflammation and colon cancer, in particular the role of diet, epithelial barrier dysfunction and microbiota. By using in vivo and in vitro approaches we observed that an impaired barrier function, which is a common feature in IBD patients, might represent an early event in intestinal tumorigenesis.In fact, we are exploring the role of polyphenols as a preventive approach to protect intestinal epithelial barrier.
Silvio Danese Publications
Selected Publications: 20-25 publications listed in details with all the contributing authors, title of the papers, journal, dates. 1) Ungaro F, Massimino L, Furfaro F, Rimoldi V, Peyrin-Biroulet L, D'Alessio ...
Silvia Restelli Technician View More
Salvatore Spanò Technician View More
Carmen Correale Technician View More
Valentina Garlatti PhD student View More
Federica Rubbino PhD students View More
Maria Quaranta PhD View More
Sudharshan Elangovan PhD View More
Federica Ungaro PhD View More
Silvia D’Alessio PhD View More
Stefania Vetrano PhD View More