Theme 5: Mechanisms of liver fibrosis

Supervisors:A/Professor William Sievert
Telephone: 9594 5525
Email: William.Sievert@med.monash.edu.au

Description:

Liver fibrosis and cirrhosis is the common end stage to all liver diseases in humans (such as infection with viral hepatitis, excessive alcohol intake or metabolic diseases).  In response to injury, it has been shown that the hepatic stellate cell (HSC), the vitamin A storing cell of the liver, is responsible for the development of liver fibrosis and cirrhosis. When HSC’s become activated they produce excess collagen and other scar components that are deposited in the liver. Over-production of this matrix results in reduced liver function and liver failure. We study mechanisms of liver fibrosis and factors that determine its progression to cirrhosis. We use animal models of liver fibrosis and cirrhosis in our laboratory to enable us to determine which factors may be important in the development of this disease and identify new therapeutic targets. Several different but interrelated honours projects in Theme 5 for the year 20109 are available. Projects will use a wide range of laboratory techniques including: Enzyme linked immunosorbent assays (ELISA), molecular biological techniques such as PCR and Real Time PCR, Western blot analysis, immunohistochemistry

1. Activin A as a marker for liver fibrosis and cirrhosis in humans

   We have recently identified activin A, a reproductive protein, as being an important component in the development of liver fibrosis. This project will aim to identify the clinical utility of activin A as a surrogate marker for liver fibrosis in humans infected with viral hepatitis B and C. It will use a range of biochemical, molecular (such as real time PCR) and histological techniques to do so.

2. The coagulation pathway in liver fibrosis and cirrhosis

   It has recently been hypothesized that several blood coagulation factors, including plasminogen, plasmin and tissue factor, may be important in the development of liver fibrosis. This project aims to further analyse the importance of these coagulation pathway members in the development of liver fibrosis. It will use a broad range of histological, immunohistochemical and molecular biology techniques. This project will be performed in conjunction with Assoc. Prof. Peter Tipping.

3. The effect of hepatitis C virus viral replication on hepatic stellate cell biology

   This project aims to further characterize the effects of HCV infection in hepatocytes results in HSC activation by using a cell culture system with a non-infectious form of the Hepatitis C virus. It will use a range of cell culture, molecular (such as real time PCR) and histological techniques to do so.

4. Mechanisms of alcohol related hepatocyte apoptosis in patients infected with viral hepatitis C.

   Patients infected with viral hepatitis C who also consume excessive quantities of alcohol typically have a poorer diagnosis and prognosis. This is likely due to the increased amount of liver cell apoptosis (cell suicide) occurring within the liver. This project will investigate the mechanisms behind this increased liver cell apoptosis. It will use a range of cell culture, molecular (such as real time PCR) and histological techniques to do so.