Hepatocytes, the main cellular component of liver tissue, possess an extraordinary ability to counteract the damaging effects of toxic agents such as alcohol, viruses and pharmacological agents. The ability to do so involves the activation of specific programmes of gene expression that result in hepatocyte survival and maintenance of liver mass and integrity.
However, when these protective programmes fail, continued hepatocyte death can cause compensatory hepatocyte proliferation aimed at maintaining overall liver mass. This may lead finally to the development and progression of Hepatocellular Carcinoma (HCC).
It is now clear that when the balance between cell survival and death is tipped towards one or the other outcome, the road to liver disease is inevitable. A key question therefore is how hepatocytes regulate the balance between survival and death. As hepatocyte death (and compensatory proliferation) plays a key role in many liver diseases, studies aimed at understanding the molecular mechanisms controlling the balance between cell death and proliferation may reveal attractive targets for the treatment of human liver diseases.
Critical molecules in the NF-kB and MAPK pathway have been shown to monitor both hepatocyte death and proliferation. By learning more about the hepatic functions of these molecules and their regulators, it might be possible to identify specific targets to prevent either cell death or proliferation, and thus ameliorate the process of cell injury.
Current areas of research
Using a combination of genetic and biochemical approaches, this Research Group aims:
1. To identify key regulators of cell death and inflammation in the liver, in order to develop specifically targeted therapeutics
2. To understand the molecular mechanisms of liver cell proliferation
3. To provide insight into the mechanisms of hepato-protection