Research lines

• Mechanisms of liver inflammation and fibrosis

  Chronic liver injury is characterized by an important inflammatory response and an increase in extracellular matrix deposition, which may lead to liver fibrosis and eventually cirrhosis. We are interested in identifying cellular and molecular mechanisms regulating the inflammatory response and liver fibrogenesis in chronic liver injury. Moreover, our laboratory is exploring how immune cell dysfunction affects liver injury and liver disease progression.

• Liver cell plasticity

  The liver has remarkable cell plasticity. Lineage tracing studies have shown the potential of biliary-to-hepatocyte as well as hepatocyte-to-biliary conversion in response of liver injury. This is particular important in the context of chronic liver diseases, which are characterized by an expansion of ductular reaction cells. Ductular reaction is a poorly characterized heterogeneous cell population comprising reactive cholangiocytes as well as immature liver progenitor cells, which may derive from both hepatocyte and biliary compartment.

  Our laboratory is interested in understanding the maintenance of cell identity in liver injury and the role and impact of ductular reaction in disease progression. Moreover, we are particularly interested in understanding the association of the ductular reaction with liver regeneration, inflammatory response and fibrosis progression.

• In vitro disease modeling

  In vitro liver models have emerged as excellent tools to better understand liver pathology, to test new therapeutic drugs and for toxicity testing studies. In our group we are interested in generating better liver cells for the development of in vitro liver models. In this regard, we have developed a methodology to differentiate hepatic stellate cells from iPSC and we have shown their potential to model liver fibrosis and for toxicity studies. Our aim is to develop 3D multicellular in vitro systems to mimic liver diseases such as alcoholic and nonalcoholic steatohepatitis.

• Group of dynamic-plasticity and heterogeneity of the tumor stroma (DynamHet)

  Directed by Dr Silvia Affò

  Tumors are not composed only by tumor cells, but they also include fibroblasts, extracellular matrix, immune cells, and vasculature, which together, are known as tumor stroma. Cancer-associated fibroblasts (CAFs) are one of the most abundant and versatile stromal cell type in the tumor microenvironment, where they are actively involved in tumor progression through a complex network of interactions with tumor cells and other stromal cells. Because of their assumed pro-tumorigenic functions, CAFs have long been considered an attractive therapeutic target. However, how CAFs change dynamically as cancers evolve, and how this may affect the overall tumour heterogeneity, remains unaddressed.

  Thanks to the recently awarded funding from the European Research Council (ERC-StG-2022), with DynamHet, we aim at elucidating the origin and evolution of CAF heterogeneity and to decipher the mediators and mechanisms that regulate CAF plasticity as the tumour advances. This is crucial for the development of effective therapies aimed at reprogramming CAFs towards therapeutically favorable phenotypes.