Liver Cell Biology Lab

Lab head: Dr Nicholas Shackel
Location: Centenary Institute of Cancer Medicine and Cell Biology

 

Ultimately we aim to understand the molecular mechanisms regulating liver fibrosis aiming to developed novel therapeutic agents as well as developing new diagnostic investigations.

 

The current focus of the research group is to further understand the role of the glycoprotein CD147 in mediating basic and fundamental aspects of tissue inflammatory responses and cancer. Our group has made the fundamental discovery that CD147 alters immune cell function and aggregation, which was previously not recognised and this is important in driving liver injury and potential the development of cancer. Taking this novel discovery from the bench through to high impact papers is the current focus of the group.

To understand the molecular mechanisms regulating liver fibrosis aiming to developed novel therapeutic agents as well as developing new diagnostic investigations.
 
The current focus of the research group is to further understand the role of the glycoprotein CD147 in mediating basic and fundamental aspects of tissue inflammatory responses and carcinogenesis. Our group has made the fundamental discovery that CD147 mediates a process of inflammatory cell aggregation, which was previously not recognised, that mediates inflammatory responses and carcinogenesis. Taking this novel discovery from the bench through to high impact papers is the current focus of the group.

Website: http://www.centenary.org.au/p/ourresearch/liver/liverimmunobiology/LiverCellBiology/
Lab members: Dr Nicholas Shackel, Dr Fiona Warner, A/Prof Susan McLennnan, Dr Thomas Tu (Post-doctoral scientist), Dr Annette Maczurek (Post-doctoral scientist), Magdalena Budzinska (Research Assistant), Christine Yee (Research Assistant), Aimei Lee (PhD Student), William d'Avigdor (PhD Student) and Robert Cheng (PhD Student)
Funding: Sydney Medical Research Foundation, Cancer Council NSW
Research approach equipment: We use a range of techniques includes genomics analysis, confocal fluorescence microscopy, flow cytometry, immunohistochemistry, quantitative PCR and Western blot analysis. Our group runs the facility for Gene Array Analysis within the Centenary Institute using both the latest Affymetrix Platform and Nimblegen.
Publications:

1.         Rahman W, Huang P, Belov L, Chrisp JS, Christopherson RI, Stapelberg PM, Warner FJ, et al. Cluster of Differentiation (CD) Antibody Array Analysis of Human Liver Disease. Liver International 2012.

2.         Shackel NA, Gorrell MD, McCaughan GW. Gene array analysis and the liver. Hepatology 2002;36:1313-1325.

3.         Shackel N, Rockey D. In pursuit of the "Holy Grail"--stem cells, hepatic injury, fibrogenesis and repair. Hepatology 2005;41:16-18.

4.      Bao W, Min D, Twigg SM, Shackel NA, Warner FJ, Yue DK, McLennan SV. Monocyte CD147 is induced by advanced glycation end products and high glucose concentration: possible role in diabetic complications. American journal of physiology. Cell physiology 2010;299:C1212-1219.


Role of Bone-Marrow Derived Cells in Progressive Liver Injury and Carcinogenesis

Primary supervisor: Nicholas Shackel

The bone marrow response to liver injury is not well understood. While it has been shown that there is a bone marrow stem/progenitor cell contribution to liver injury, the responding cells are poorly characterized and their physiological relevance remains unclear.

Hypothesis and Aims: We hypothesize that there is a specific bone marrow stem cell mobilization with liver injury. Furthermore we hypothesize that bone marrow derived stem cells that mobilize with liver injury may contribute to the development of liver cancer.

Methods: The initial phase of this project will compare the expression of stem cells markers on a rodent stem cell line using immunohistochemistry/immunofluoresence and flow cytometry. Further we plan to use conditioned media to study the events involved in the differentiation of the stem cell line into hepatocytes, endothelial and cholangiocyte cell lineages. The final part of this project will study the effects of the stem cells administered to rodents in models of liver injury.

Skills: This project will utilise real-time RT-PCR, cell isolation, magnetic bead separation and flow cytometry techniques. It is envisaged that the student who undertakes this project will become proficient in all of these methods whilst being exposed to a number of other general laboratory techniques.

Conclusion and Significance: Our results to-date support the hypothesis that a population of liver-specific stem cells reside within the bone marrow and are recruited to the liver with injury.It now needs to be determined what role these recruited cells have in liver pathobiology.


Discipline: Infectious diseases and Immunology
Keywords: Liver Disease, Stem cells, Stem cells
Contact: Email Nicholas Shackel