Plasticity, Fibrosis and Cancer Lab

The challenge

Fibrosis is a pathological wound healing response leading to tissue scarring and organ failure. Moreover, fibrosis represents a milieu favoring cancer initiation in many organs, constitutes a major component of the tumor microenvironment and could arise as a side effect of oncological therapies. Overall it is estimated that fibrosis is responsible for 45% of the deaths worldwide and no effective anti-fibrotic therapy is currently available. By using unique in vivo mouse models and cutting-edge technologies, we aim to understand the fibrotic process in neoplastic and non-neoplastic settings utilizing approaches which allow to comprehensively analyze at all the involved cellular players.

Main Research Areas

Mechanisms of tissue damage response in fibrosis

Fibrosis is the final outcome of a cascade of events leading to tissue scarring and loss of functionality. While it was usually considered a disease of fibroblasts, we demonstrated that the epithelial and endothelial injury responses, namely epithelial- and endothelial-to-mesenchymal transition (EMT and EndMT, respectively) orchestrate the fibrotic response by impairing regeneration, affecting tissue functionality and fueling inflammation. We are currently deepening the investigation of the functional role of epithelial and endothelial plasticity in the setting of acute and chronic injury responses by utilizing in vivo and in vitro models as well as validation in patient-derived tissues.

Role of epithelial plasticity in inflammation-induced cancer initiation

The process of EMT has traditionally been linked to the metastatic cascade but little is known about its role in the initial phases of the tumorigenesis. Considering the new identified role for EMT in inflammation and fibrosis, we seek to investigate the role of EMT in the early phases of malignant transformation in those cancers arising from chronic inflammatory conditions such as intestinal and pancreatic cancer.