Progetto FRRB ID 4976687- Cholangioids to dissect the genetic drivers of atypical Primary Sclerosing Cholangitis (CILIA)
Dati del progetto
Principal Investigator |
Dr. Alessandro Cherubini |
Ente ospitante |
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico |
Area Tematica |
Malattie Rare |
Data di inizio Progetto |
16/12/2024 |
Data di fine Progetto |
15/12/2027 |
Importo assegnato |
498.200,00 € |
Tipo Progetto |
Individuale |
PROJECT AIMS
Primary sclerosing cholangitis is a progressive, and often fatal bile duct disease, with an estimated prevalence in Western countries of ∼1 in 10,000. Biliary affection in PSC is chronic and represented by cholestasis, inflammation, and concentric fibrosis, which can lead to the development of cirrhosis and frequently progress to cholangiocarcinoma. The etiology is most likely immune mediated multifactorial, triggered by environmental factors in a genetically susceptible host. Primary cilia are organelles that play a key role in the differentiation of cholangiocytes and thus also in the development of cholangiopathies, immune cell invasion, and the fibrotic process. This project aims to:
- Develop three-dimensional multicellular models of bile ducts (called cholangioids) by integrating primary stromal cells and macrophages with liver organoids;
- Develop and test a new advanced extracellular vesicle-based gene editing system, called VeCas, which carries a modified version of Cas9 fused with a reverse transcriptase and guide RNA for prime editing.