Surgery (Division of Pediatric Surgery)
Keck School of Medicine
Childrens Hospital Los Angeles
- Developmental Biology
- Stem Cell Biology
- Cell Cycle
- Growth & Proliferation
Research OverviewEnd-stage liver disease is the consequence of chronic liver damage most commonly caused by viral or alcoholic hepatitis. The scope of disease is massive. Nearly 500 million people worldwide harbor chronic Hepatitis B or C infections. Alcohol consumption is the leading risk factor to health in developing countries. In the U.S., alcohol is the most common cause of liver-related morbidity and mortality. If needed, organ replacement is accomplished by liver transplantation, but this is limited by donor organ availability. Accordingly, efforts directed towards both prevention and treatment of end-stage liver disease remain very relevant in the landscape of healthcare today. Since organ regeneration represents in part a recapitulation of organogenesis, we study the interaction between hepatic stellate cells and progenitor cells during hepatogenesis and during regeneration to better understand how the liver regenerates itself.
We have recently shown that embryonic hepatic stellate cells (HSC) secrete Fibroblast Growth Factor (FGF)-10, which binds to the receptor FGFR2b expressed on hepatoblasts, or embryonic hepatic progenitor cells (HPC), to promote cell proliferation and survival through beta-catenin activation (Berg et al, Hepatology 46, 2007). Our research efforts now focus in three main areas: (1) characterization of the role of mesenchymal-epithelial cell interactions during hepatogenesis, (2) characterization of the role of FGF10/FGFR2b signaling during liver regeneration, (3) the role of FGF10/FGFR2b signaling in postnatal hepatic progenitor cell proliferation and differentiation.