Grant: Project Grant

Liver disorders are one of the leading causes of death worldwide. Non-alcoholic fatty liver disease affects over 7 million Canadians and liver cancer is the fasted rising cancer in Canada. Currently, the treatments for chronic liver disease are focused on slowing progression and minimizing complications, such as portal hypertension. One of the effective cures for liver disease, liver transplantation is highly dependent on donor resource with very stringent criteria for patients who can donate and receive such surgery. Recent advances in the generation of hepatocytes, the main functional cell in the liver, from human pluripotent stem cells (hPSCs) have excited researchers by providing a potential source of cells for liver transplants, drug testing and bioartificial liver devices. These cells also provide a model to study human liver development so that we can better understand liver biology. Current methods of making hepatocytes from hPSCs do not yet result in fully functional hepatocytes and do not consider how other types of cells are necessary for a proper functioning liver. We need to better understand how the liver is formed and how the hepatocytes interact with other cell types to create a fully functional liver. Our work will focus on how the liver cells are initially made using hPSCs. We will use two different types of systems to study how genes are regulated in these hepatocyte progenitors, both as a flat, 2D cultures and in multi-cellular, 3D organoid cultures, often called 'mini-livers'. We will use state of- the-art methods to understand how regulators of genes work with the chromatin and epigenetic environment to promote liver formation.