Our research aims to:
- Understand the molecular and cellular mechanisms of liver damage and repair with particular focus on diseases of the biliary tract or cholangiopathies.
- Find treatments that can reduce the progression of liver disease.
- Understand the mechanisms of liver carcinogenesis and find new therapeutic solutions for patients with primary liver cancer (hepatocellular carcinoma and cholangiocarcinoma).
- Improve outcomes and health care delivery for patients with liver diseases
A long-standing focus of the lab is to study the biology of biliary epithelial cells (cholangiocytes) and to understand the pathophysiology of acquired, congenital and neoplastic diseases of the biliary tract (cholangiopathies). Cholangiopathies are rare diseases but are frequent as a group and represent one of the major unmet needs in hepatology.
A major problem in cholangiocyte research is the lack of in vitro human models to study the pathogenesis of cholangiopathies and to validate potential therapeutic targets. Our current knowledge of the field derives mainly from studies using in vivo animal models or in vitro primary cell culture systems and immortalized cell lines. While the use of rodent models suffers often from a lack of phenotype reproducibility, primary human cholangiocytes are difficult to isolate, de-differentiate after a few passages, and in very short supply. Furthermore, immortalized cell lines do not faithfully recapitulate normal physiological functions of cholangiocytes.
Cholangiocarcinoma (CCA) is an aggressive tumor whose incidence is increasing. CCA is characterized by a strong desmoplastic reaction, a strong invasiveness and a very poor prognosis. Surgical treatment is the most used, but the results are poor because most CCAs, at the time of diagnosis, already have metastases to the local lymph nodes. The lack of effective therapies reflects the uncertainties regarding the molecular mechanisms that govern tumor progression in CCA.
Chronic liver diseases (CLD) impose a major health burden worldwide affecting the health and lives of many individuals and families as well as substantial costs for individuals and payers. Hepatologists practice a high intensity cognitive sub-specialty,