PROGETTO CILIA

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.