Liver disease and carcinogenesis


Student project opportunities

Understanding the cellular and molecular basis of liver progenitor cell transformation to cancer

Research area: cancer
Chief supervisor: Professor George Yeoh
Project suitable for: Honours
Essential qualifications: BSc with major in Biochemistry, Molecular Biology or Genetics
Start date: Semester 1 or Semester 2

Project outline
Our laboratory has generated many liver progenitor cell lines that can be propagated and directed to differentiate into cholangiocytes and hepatocytes. The main thrust of the lab is to generate cells that can be used for cell therapy for transplant to alleviate symptoms related to liver pathology. Our lab, as well as our collaborators which have received these cell lines have found that following extensive passaging, some lines transform and become cancerous. When we compare the pattern of gene expression between the tumorigenic and non-tumorigenic LPCs, there are several oncogenes that are up-regulated, and several tumour suppressor genes that are down-regulated. In particular, we have focussed our attention on transcripts of p53 and the INK/Arf locus.

Liver diseaseThere are two possible mechanisms to explain the progression of tumorigenicity that we observe with passaging the cells. One model (1) proposes that at the beginning, extremely rare tumorigenic LPCs are present and they increase in number with passaging. The alternate model (2) hypothesises that no tumorigenic cells are present initially, but these accumulate mutations progressively and ultimately tumorigenic LPCs appear in extensively passaged cultures. The diagram below contrasts these models. The aim of the project is to determine which model applies to the transformation of LPCs during culture.  Two approaches will be used. First the transformed cells will be selected by virtue of their ability to grow in soft agar. The size and growth properties of the colonies will be determined. The colonies will be expanded and expression of p53, INK and Arf will be determined at the level of transcript abundance by qPCR.

Contact
Professor George Yeoh -  george.yeoh@uwa.edu.au

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