Mechanisms of Liver Fibrosis and Hepatocellular Carcinoma
Summary
Mechanisms of Liver Fibrosis and Cancer
Supervisor(s)
Research Location
Centenary Institute of Cancer Medicine and Cell Biology
Program Type
Masters/PHD
Synopsis
No matter what the cause of liver injury (viral hepatitis, alcohol, bile duct obstruction) most liver diseases result in a common disease progression. Chronic liver injury disrupts the normal structure and function of the liver by initiating hepatic fibrosis, a process that leads to destruction of the normal liver architecture, loss of functioning hepatocytes and bile duct epithelial cells (cholangiocytes) and the development of liver cirrhosis, the endstage of liver fibrosis. The sequelae of cirrhosis include liver failure and hepatocellular carcinoma (HCC). The global health burden from liver disease is immense, with in excess of 450 million people infected with viral hepatitis and HCC the fifth most common human malignancy. Therefore, a better knowledge of the process of fibrosis is essential. This research will investigate mechanisms of liver fibrosis with a particular emphasis on the role of zinc metallopeptidases, such as angiotensin-converting enzyme 2 (ACE2) and more recently matrix metalloproteases (MMP1, 2, 3, 9, 13), in this process. Understanding the mechanisms regulating expression and function of these enzymes and the cell biology of hepatocytes will allow us to dissect their roles in normal and injured liver and create new opportunities to develop novel strategies to minimise or resolve fibrosis.
Additional Information
Techniques included in the projected listed:
- Molecular Biology
- Microarrays (gene and microRNAs)
- Protein Biochemistry (Western blotting, target protein silencing,
- Protein-protein interactions studies)
- Cell Culture
- Microscopy (light and confocal)
- Animal models of liver injury
- The Role of Angiotensin-Converting Enzyme-2 and Liver Injury
- Biliary Epithelial to Mesenchymal Transition
- The Role of the Hedgehog Pathway in Biliary Liver Disease
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Keywords
Biliary Fibrosis, Hepatic injury, Liver disease, Liver cirrhosis, enzymes, Matrix metalloprotease, Gene microarray, Epithelial to mesenchymal transition, Liver & hormonal disorders, Cell biology, Human body
Opportunity ID
The opportunity ID for this research opportunity is: 136
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