Ricerc@Sapienza

Cholangiopathies represent a heterogeneous group of human liver diseases comprising several conditions affecting the biliary tree. Cholangiocarcinoma (CCA) includes a heterogeneous group of cancers affecting the biliary tree. The primary target of these diseases is represented by cholangiocytes, the epithelial cells lining the bile ducts. Despite progress in the understanding of cholangiopathies and CCA, a considerable translational gap remains between putative targets and effective patient therapies. This is in part due to limited definition of the functional heterogeneity and interactome of cell lineages that contribute to these diseases.
The GeoMx Digital Spatial Profiler (DSP) and NCounter® Sprint Profiler is an integrated workstation developed by Nanostring® and represents a benchtop multiplex system that combines the advantages of high-throughput molecular (both proteomic and transcriptomic) analysis with the spatial definition of histological samples, allowing to perform molecular analysis from formalin-fixed, paraffin-embedded samples and to obtain data into a morphological context.
The general aim of this project is to unveil the complete identity, function, and molecular profile of cells involved in cholangiopathies and CCA. This could be pursued thanks to the use of full potentiality of the GeoMX DSP platform. Since cholangiopathies and CCA are characterized by cross-interaction among parenchymal cells (i.e. hepatocytes, cholangiocytes, stem/progenitor cells), myofibroblast population and inflammatory cells, the morphological distinction at single cell level will ensure a precise cell recognition and the identification of eventual modifications in the molecular profile induced by disease state. The multi-omics analyses will generate large datasets that could be processed by artificial intelligence approaches (e.g. machine learning and network medicine), that could lead to identify novel pathogenetic, diagnostic, and therapeutic targets.