Role of Notch signalling on the regulation of liver cancer stem cells

Summary

Suits candidates for PhD or Master's degree.

Supervisor(s)

Dr Liang Qiao, Professor Jacob George

Research Location

Westmead - Westmead Millennium Institute

Program Type

Masters/PHD

Synopsis

To develop more efficient therapeutic approaches for HCC, a better understanding of the molecular mechanisms involved in the development, progression, metastasis and treatment-resistance of HCC is critical. The Notch signalling pathway is an evolutionarily conserved signalling pathway that plays a major role in mediating cell proliferation, survival, apoptosis and differentiation in several solid tumours including liver cancer. Besides being essential for hepatoblasts to differentiate into duct plate cells and form branching tubules, Notch signalling has been demonstrated to be involving in HCC. However, the published results on the role of Notch signalling in HCC formation are controversial and conflicting as both oncogenic and tumour suppressive functions of Notch signalling have been reported in HCC. More studies on the role of Notch signalling in HCC are warranted. Notch signalling consists of 5 ligands, 4 receptors and several downstream targets. They are ubiquitously expressed in many normal and malignant tissues. It is now believed that Notch pathway is one of the major signalling pathways controlling cell fate, differentiation, and cancer stem cell (CSCs) functioning. Although CSCs only constitute a small subset of cancer cells, they are the "root" of the cancer tissue bulk and are responsible for the generation of distant metastasis and relapse after therapy. The existence of CSCs has been shown in many different solid tumours, including HCC. Elimination of liver cancer stem cells (LCSCs) may shed light on a potential novel therapy for HCC.

Published data and our own studies have demonstrated that Notch is a key regulator for LCSCs. However, little is know on how Notch signalling is involved in the regulation of LCSCs. In this project, we will investigate how Notch signalling plays a regulatory role in LCSCs, with a ultimate focus on whether Notch signalling can be used as a potential target for stem cell based cancer therapy. This project involves many cellular and molecular biological techniques, flow cytometry, and small animal experiments.

Additional Information

About the Storr Liver Unit
The Western Clinical School's Storr Liver Unit investigates the pathogenesis of liver disease, and the diverse causes of liver injury, such as drugs and toxins, metabolic factors and viruses. Internationally acclaimed, the Unit has made substantial contributions to defining how the liver responds to injury, and how genes involved in the metabolisms of drugs and toxic products of liver metabolism are regulated.
Liver cancer is Australia's fastest growing cancer, and this is an opportunity to take a role in the research of this emerging health focus. The Unit is well funded and thus there is the opportunity to employed cutting edge techniques and tools to bring each project to fruition. Joining a successful research team with expertise in liver disease and cancer, there will also be opportunity to collaborate with internationally-renowned cancer researchers at the Westmead Millennium Institute. As part of the community of over 400 researchers based on the Westmead campus, there will be the possibility to utilise the Institute's state-of-the-art molecular, translational and cell biological facilities.

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Keywords

Notch signaling, Liver cancer, Stem cells, regulation

Opportunity ID

The opportunity ID for this research opportunity is: 1315

Other opportunities with Dr Liang Qiao

Other opportunities with Professor Jacob George