Faculty of Health and Medical Sciences

Liver Development and Carcinogenesis Laboratory

 

Prof. George Yeoh

Laboratory:
Liver Development and Carcinogenesis
Location:
Harry Perkins Institute of Medical Science
Websites:

Liver biopsy from a patient with alcoholic liver disease, stained for liver progenitor cell markers (red and green). Red; GCTM-5, Green; Pan Cytokeratin, Blue; DAPI (nuclei). Image courtesy of Anne Kramer (PhD student).


Area of Expertise

Prof. George Yeoh has an extensive and protracted interest in liver progenitor cells (LPCs), and has an established international reputation as an expert in the field of liver stem cell research. LPCs are bipotential cells that are able to generate hepatocytes as well as bile duct cells. Prof. Yeoh and his team were the first to report the existence of LPCs in a rat model of alcoholic liver disease, and later their presence in human chronic liver diseases including chronic alcoholic liver disease, hemochromatosis and hepatitis C. LPCs play an important role in chronic liver regeneration, but have also been implicated in the development of liver cancer, in particular hepatocellular carcinoma (HCC). The laboratory's main objectives include;

  1. Develop a serum-based diagnostic assay that can detect HCC early.
  2. Develop new markers that can distinguish tumorigenic LPCs from non-tumorigenic LPCs.
  3. Identify agents that can target and inhibit tumorigenic LPCs.

Top 10 Publications

  1. Viebahn, C.S., V. Benseler, L.E. Holz, C.L. Elsegood, M. Vo, P. Bertolino, R. Ganss, and G.C. Yeoh, Invading macrophages play a major role in the liver progenitor cell response to chronic liver injury. J Hepatol, 2010. 53:500-7. Evidence that liver macrophages underpin the LPC response. This links inflammation and liver progenitor cells.
  2. Tirnitz-Parker, J.E., C.S. Viebahn, A. Jakubowski, S.K. BR, J.K. Olynyk, G.C. Yeoh, and B. Knight, Tumor necrosis factor-like weak inducer of apoptosis is a mitogen for liver progenitor cells. Hepatology, 2010. 52:291-302. Highlights TWEAK's importance in regulating LPCs, and merited a Hepatology editorial comment. It identifies TWEAK as an inflammatory cytokine that underpins liver progenitor cell growth.
  3. Yeoh, G.C., M. Ernst, S. Rose-John, B. Akhurst, C. Payne, S. Long, W. Alexander, B. Croker, D. Grail, and V.B. Matthews, Opposing roles of gp130-mediated STAT-3 and ERK-1/2 signaling in liver progenitor cell migration and proliferation. Hepatology, 2007. 45:486-494. This report identifies signaling pathways that drive liver progenitor cell proliferation and differentiation into hepaotcytes
  4. Knight, B., B. Akhurst, V.B. Matthews, R.G. Ruddell, G.A. Ramm, L.J. Abraham, J.K. Olynyk, and G.C. Yeoh, Attenuated liver progenitor (oval) cell and fibrogenic responses to the choline deficient, ethionine supplemented diet in the BALB/c inbred strain of mice. J Hepatol, 2007. 46:134-41. This study links liver progenitor cells with the pathology of liver fibrosis and it opened up the possibility of attenuating fibrosis by manipulating liver progenitor cells.
  5. Dumble, M.L., E.J. Croager, G.C.T. Yeoh, and E.A. Quail, Generation and characterisation of p53 null transformed hepatic progenitor cells: oval cells give rise to hepatocellular carcinoma. Carcinogenesis, 2002. 23:435-45. Describes the first time transformed liver progenitor cells are established from a transgenic mouse that is cancer prone.
  6. Akhurst, B., E.J. Croager, C.A. Farley-Roche, J.K. Ong, M.L. Dumble, B. Knight, and G.C. Yeoh, A modified choline-deficient, ethionine-supplemented diet protocol effectively induces oval cells in mouse liver. Hepatology, 2001. 34:519-22. This is a highly cited publications that describes a physiological model for inducing fatty liver followed by development of liver cancer in mice.
  7. Knight, B., G.C. Yeoh, K.L. Husk, T. Ly, L.J. Abraham, C. Yu, J.A. Rhim, and N. Fausto, Impaired preneoplastic changes and liver tumor formation in tumor necrosis factor receptor type 1 knockout mice. J Exp Med, 2000. 192:1809-18. This reports the link between liver progenitor cells and cancer by showing a reduction in tumour incidence in mice which have fewer liver progenitor cells.
  8. Lowes, K.N., B.A. Brennan, G.C. Yeoh, and J.K. Olynyk, Oval cell numbers in human chronic liver diseases are directly related to disease severity. Am J Pathol, 1999. 154:537-41. This is the first report of increased liver progenitor cells in patients with chronic liver disease which predispose them to developing hepatocellular carcinoma. It has been cited over 100 times.
  9. Yeoh, G.C., F.A. Bennett, and I.T. Oliver, Hepatocyte differentiation in culture. Appearance of tyrosine aminotransferase. Biochem J, 1979. 180:153-160. This finding showed that it is possible to transition fetal liver cells into adult cells in culture and such cells recapitulated events in the fetus.
  10. Newman, S.A., J. Birnbaum, and G.C. Yeoh, Loss of a non-histone chromatin protein parallels in vitro differentiation of cartilage. Nature, 1976. 259:417-418. This publication showed that proteins that bound to DNA changed when cartilage cells differentiated. This suggested that transcription factors directed and determined cell fate.


Publications with CCTRM byline

  1. Diepeveen, L.A., Watson, M.E., McSpadden, S.B., Strauss, R.P., Callus, B.A. and Yeoh, G.C. Epigenetic Modulators Enhance Constitutive and Liver-Specific Reporter Expression in Murine Liver Progenitor Cell Lines. Tissue Engineering Part C: Methods. July 2015, 21(10): 1080-1087.
  2. Watson, M.E., Diepeveen, L.A., Stubbs, K.A., and Yeoh, G.C. Glycoslylation-related Diagnostic and Therapeutic Drug Target Markers in Hepatocellular Carcinoma. J. Gastrointestin Liver Dis. 2015 Sep;24(3):349-57.


Recent Grant Successes

  1. Prof G. Yeoh (CIB) et al. Micro RNAs and liver cancer. NHMRC Project Grant 2015
  2. Prof G. Yeoh (CIA) et al. Understanding and applying macrophages. NHMRC Project Grant 2013
  3. Prof G. Yeoh (CID) et al. Human amnion epithelial cells and liver repair.  NHMRC Project Grant 2014

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