Grant: Project Grant

The liver is constantly exposed to toxic chemicals from food and medication that cause inflammation. Normally, the liver is able to fend off these insults and repair itself quite rapidly. However, when the onslaught is chronic, for example, during chronic alcohol abuse or infection by hepatitis viruses, the inflammation persists and outpaces the normal repair process. This results in persistent liver damage, leading to a condition known as liver fibrosis, which can progress towards cirrhosis, wherein the vital liver functions are compromised and often leads to liver cancer. Liver cancer ranks as the fifth most common cancer and the third leading cause of cancer-related death. Most liver cancer patients die within one year due to late diagnosis and lack of effective treatment. While the liver cancer is difficult to treat, early detection of fibrosis and development of anti-fibrotic interventions could prevent the advancement of disease and its progression towards cancer. Inflammation in general is mediated by a group of proteins called 'inflammatory cytokines', which have a normal function as long as their activity is controlled. This is achieved by a variety of mechanisms, of which the control exerted by a family of proteins called 'Suppressor of cytokine signaling' appears to be very important. This is supported by data from human patients who do not express the SOCS1 protein in the liver, and from our own studies using mice lacking SOCS1. We propose to use this mouse models to gain a better understanding of how SOCS1 regulates liver fibrosis. This knowledge could lead to development of new therapeutic approaches to treat liver fibrosis, and thus diminish patient suffering and healthcare burden from cirrhosis and liver cancer.