Mercoledì 17 Aprile 2024, ore 13
Edificio Asclepio U8-Aula 3
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Fibropolycystic liver diseases (FLDs), among which Caroli's disease (CD) and congenital hepatic fibrosis (CHF) are rare autosomal recessive pathologies (incidence, 1:20,000/100,000) caused by mutations in PKHD1 gene, affecting both paediatric and young adult populations. CD and CHF are characterized by the presence of biliary cysts surrounded by stark fibrosis and abundant inflammatory infiltrate, causative of recurrent cholangitis, portal hypertension, variceal bleeding, and, in the 10/20% of cases, cholangiocarcinoma (CCA), a rare and aggressive tumor of the biliary tract, whose 5-year survival is only the 5/10%. Due to the lack of knowledge of the mechanisms leading to the development of CD/CHF, these diseases are actually orphan of effective pharmacological treatments and of reliable biomarkers able of predicting their outcome, including the development of CCA. In this seminar, I will illustrate the results obtained in recent years in the field of the pathogenesis of FLDs, with particular emphasis on the deregulation of epithelial-mesenchymal interactions and on the derangement of the planar cell polarity of cholangiocytes, responsible for the fibroinflammatory response typical of these diseases. Finally, I will focus on the mechanisms, still poorly known, putatively involved in their neoplastic transformation to CCA.
Massimiliano Cadamuro
Dr Massimiliano Cadamuro is actually Associate Professor of General Pathology at School of Medicine and Surgery of University of Milan-Bicocca. He obtained both the degree in Biological Sciences and the PhD in regenerative medicine and biology from the University of Padua. Dr Cadamuro served as post doc fellow at the Center for Liver Research (CeLiveR, Bergamo), University of Padua, and University of Milan-Bicocca and as Assistant Professor at the Dept. of Molecular Medicine in Padua. He also attended, as visiting scientist, the Dept. of Morphology and Molecular Pathology at the University of Leuven (Belgium), the Hormone and Metabolic Research Unit (HMRU) at the University of Louvain la Neuve (Belgium), and the Digestive Disease Section at Yale University (USA). His scientific interest has always been aimed at the study of chronic fibroinflammatory diseases of the biliary tree (biliary atresia, Caroli’s disease, congenital hepatic fibrosis, cystic fibrosis-related liver disease, Alagille syndrome), epithelial-mesenchymal interactions in cholangiocarcinoma and mechanisms of neoplastic transformation of the biliary epithelium.