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Fishing for metabolic clues: Role of the Hippo/Yap pathway in reprogramming metabolism in liver cancer

Sir Peter MacCallum Department of Oncology, University of Melbourne

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Dr A. Cox Applications accepted all year round

About the Project

The Hippo/Yap pathway is an evolutionarily conserved cascade that plays a fundamental role in governing organ size control, stem cell homeostasis and cancer. The Hippo/Yap pathway is regulated by a range of environmental cues including nutrient status. Although many of the inputs into the Hippo pathway have been identified, less is known about the Yap target genes responsible for tissue growth. Using a combination of metabolomic and transcriptomic approaches in zebrafish, we have discovered that Yap reprograms glutamine metabolism in vivo to stimulate nucleotide biosynthesis and fuel premalignant liver growth.

Building on this initial investigation, we currently have research projects that aim to 1) Examine how Yap coordinates nutrient sensing to metabolic output in the liver. 2) Elucidate the mechanisms by which Yap reprograms metabolism to fuel liver growth in the context of regeneration and cancer.

The students will use a combination of innovative biochemical, genetic and imaging approaches in zebrafish to identify the metabolic dependencies of tissue growth during regeneration and cancer.

In the Cox laboratory, we investigate mechanisms by which oncogenic pathways reprogram metabolism to fuel liver growth in the context of development, regeneration and cancer. Our research team uses a combination of metabolomic and transcriptomic approaches in zebrafish (Danio rerio) to study metabolic reprogramming in vivo. Our ultimate vision is to identify therapeutic strategies that exploit the metabolic vulnerabilities of liver tumors.

Peter MacCallum Cancer Centre in Melbourne Australia’s only public hospital solely dedicated to cancer, and home to the largest cancer research group in Australia. Cancer is a complex set of diseases, and modern cancer research institutes such as Peter Mac conduct research covering a diversity of topics that range from laboratory-based studies into the fundamental mechanisms of cell growth, translational studies that seek more accurate cancer diagnosis, clinical trials with novel treatments, and research aimed to improve supportive care.

All students engaged in postgraduate studies at Peter Mac are enrolled in the Comprehensive Cancer PhD (CCPhD) program, regardless of which university they are enrolled through. The program is managed by the Sir Peter MacCallum Department of Oncology (The University of Melbourne), based at Peter Mac.

The Comprehensive Cancer PhD program builds on established conventional training for cancer research students providing a coordinated program of skills, research and career training in addition to usual PhD activities. The program is designed to complement existing PhD activities and provides opportunities to develop professional skills that will help candidates to fulfil their career ambitions.

Funding Notes

All PhD students at Peter Mac must have a scholarship from The University of Melbourne or through another government, trust or philanthropic organisation. Before applying for a scholarship, you must have agreed on a project with an institute supervisor.

For further information about the university application process, see:

For further information regarding scholarships (both local and international), see:
Closing dates for applications for scholarships to commence in 2020: Round 1 -31 October 2019; Round 2 - 31 Jan 2020; Round 3 - 15 May 2020.

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