Hepatic stellate cells and hepatic stellate cell-derived extracellular matrix in acute liver injury.

• Applicant: Sonakshi Bhattacharjee, Ph.D.
• Subject Area: Gastroenterology ; Cell Biology
• Term: from 2018 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 417747618

Hepatic stellate cells (HSC) are the predominant collagen-producing cell type in the injured liver. Following liver injury, HSC undergo a phenotypic change, transforming from vitamin A-storing, lipid droplet-containing cells to myofibroblast-like cells that produce extracellular matrix. In the past 2 decades, research has been largely focused on the disease-promoting role of HSC in chronic liver disease. However, the role of HSC during acute disease, such as toxic-drug induced injury or pathogen associated liver disease as well as potential protective functions of the HSC-mediated wound healing response remain mainly unexplored. We hypothesize that HSC and HSC-produced ECM provide important protective functions following acute liver injury or infection, and that this beneficial response only becomes maladaptive when the underlying disease cannot be cured and injury becomes chronic. This project seeks to understanding the role of HSC in the context of acute liver injury and unravel mechanism by which HSC and HSC-derived ECM may protect the liver. Using novel HSC ablation and HSC-specific knockout models, we will explore how HSC and HSC-derived ECM regulate liver injury and epithelial cell behavior in the setting of injury, focusing on cytoprotective and mechanosensitive signaling pathways in hepatocytes through receptor-dependent and receptor-independent routes.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Robert F. Schwabe