Сяобо Ван, доктор философии

Премия за пилотное исследование
50,000 XNUMX долларов США за год

The Trustees of Columbia University in the City of New York

Deciphering Hepatocyte–Macrophage–Stellate Cell Crosstalk in MASH Fibrosis Using Human Organoids and iPSCs

Metabolic dysfunction–associated steatohepatitis (MASH) is a serious and increasingly common liver disease that can lead to scarring of the liver (fibrosis), liver cancer, and death. Fibrosis is the main factor that determines how severe the disease becomes, but there are currently no effective treatments that directly stop or reverse this scarring. One reason for this gap is that we still do not fully understand how liver cells communicate with other cells to drive fibrosis. In particular, liver cells (hepatocytes) can send signals that activate scar-forming cells and immune cells, which together worsen liver damage. My research has identified a new pathway that may explain how this process occurs. I found that a protein in liver cells, called caspase-8, increases in MASH and triggers the release of another protein called meteorin. Meteorin can directly activate scar-forming cells, leading to fibrosis. In addition, meteorin can stimulate immune cells in the liver to become more inflammatory, which further promotes scarring through a second pathway. In this project, I will study how caspase-8 causes liver cells to produce meteorin and how meteorin drives inflammation and fibrosis. I will use advanced human cell models that mimic the liver to better understand these processes. This research will uncover new ways that liver disease develops and progresses. Ultimately, it may identify new targets for treatments that can prevent or reduce liver scarring in patients with MASH.