Grant: Operating Grant

Keratins constitute a family of cytoskeletal proteins present in epithelial cells of both keratinizing (e.g. skin) and non-keratinizing (e.g. liver) tissues. Monoclonal antibody technology has established them as reliable markers of epithelial cells when they emerge from stem cells. However, their role(s), particularly in internal organs like liver, remains unclear. The data accumulated largely by us in recent years suggest that keratins play a pivotal role in the liver cell responses to death-receptor and insulin-receptor stimulation and to oxidative stress. This research proposal uses mice lacking keratins in their liver as a model system to investigate how keratins regulate these cellular activities. The experimental strategies are based on use of complementary molecular biology, biochemistry and high-resolution microscopy tools. The proposed research will shed new light on the involvement of keratins in liver disease development, for instance when mutations in human keratin genes result to liver cirrhosis.