Grant: Project Grant

The term "liver disease" comprises over 100 types of disorders. However, the most common form of chronic liver disease is Non-Alcoholic Fatty Liver Disease (NAFLD), which affects an estimated 30-46% of the population in the US. In Canada, over 2,000 deaths per year are due to liver disease and a further 1,700 deaths from liver cancer. As in the US, obesity is the leading cause of liver disease, with over-exposure to common chemicals or medications and viral infections such as hepatitis, being major contributors. Regardless of the initiating factor, chronic liver disease can cause permanent liver damage and scarring that will progress to cirrhosis, poor liver function and eventually may advance to hepatocellular carcinoma (HCC). Currently, there is no cure for cirrhosis. Treatment focuses on slowing progression and minimizing complications, such as portal hypertension. When it is no longer possible to manage the complications, a liver transplant is required, but demand for transplants far exceeds available donor tissue. Recent advances in the differentiation of human pluripotent cells (hPSCs) into hepatocytes has excited researchers by providing a potential source of cells for liver transplants, drug testing and bioartificial liver devices. However, current methods of growing liver from hPSCs do not yet result in fully functional cells. Thus, methods to improve donor tissue expansion or the derivation of liver tissue from hPSCs require a better understanding of the factors that promote and maintain liver cells proliferation and differentiation. Our reserach will focus on how cells communicate and regulate the expression of genes in the liver. Using mouse as a model system, we will study how the different cell types in the liver are made and allow the liver to grow.