Liver Research

The role of activin and follistatin in hepatic regeneration and fibrosis

Supervisor:  Associate Professor William Sievert

The liver responds to injury by a common process of wound repair with progressive fibrosis that in some people leads to cirrhosis, or end stage liver disease. The cell responsible for producing fibrosis is the hepatic stellate cell. We are interested in how the stellate cell is regulated and particularly in its production of a novel protein call activin. In collaboration with investigators at the Monash Institute for Reproduction and Development, we have characterised the expression of activin and its natural inhibitor, follistatin, in an animal model of cirrhosis. This project will further examine the cellular action of follistatin on the proliferation, function and death of other resident liver cells. The techniques involves include isolation of specific hepatic cell types from whole liver and propagation in cell culture, ELISAs, immunohistochemistry including methods to detect apoptosis and proliferation of stellate and other target cells, and RT-PCR for mRNA quantitation.

Is hepatocyte apoptosis an important mechanism in liver injury?

Supervisor: Associate Professor William Sievert

Apoptosis or programmed cell death may be as important as necrosis in causing liver injury. We have shown that apoptosis is increase in patients infected with the hepatitis C virus (CV), a common cause of human liver injury which in some patients may lead to cirrhosis and liver cell cancer. This effect can be augmented by alcohol abuse. The Liver Unit and Monash Medical Centre has access to stored sera and liver tissue from patients with chronic viral hepatitis and a number of other liver diseases. This project aims to further define the prevalence of hepatocyte apoptosis in different stages of liver injury (from the earliest signs of fibrosis to established cirrhosis) and the mechanisms by which apoptosis may be linked to liver fibrosis. Techniques involved include immunohistochemistry including for early detection of apoptosis through caspase activation. ELISAs will be used to identify cytokines involved in apoptosis regulation.