Many of the major risks factors for developing liver cancer such as alcohol, obesity, smoking and toxin exposure share in common a role for oxidative stress. Nrf2 is a transcription factor activated by oxidative stress that orchestrates an adaptive response remodeling metabolism and promoting cytoprotection. Recent studies have identified that the Nrf2 pathway is frequently mutated in liver cancer (~12% tumors), causing activation of the pathway in the absence of oxidative stress. We have used transcriptomic and metabolic profiling in Nrf2-/- zebrafish to examine the role Nrf2 plays in remodeling metabolism during liver development and regeneration.
Building on these preliminary studies, this project aims to 1) Generate a gain of function Nrf2 mutant (Nrf2D29H), frequently recovered in cancer, and characterize the effect the mutation has on metabolic reprogramming, and/or to 2) Examine how deregulation of Nrf2 remodels metabolism to stimulate liver tumorigenesis. The student will use a combination of innovative biochemical, genetic and imaging approaches in zebrafish to identify the metabolic dependencies of tissue growth in liver regeneration and cancer.
The Cox laboratory investigates 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. https://www.petermac.org/research/labs/andrew-cox
Peter MacCallum Cancer Centre, Melbourne Australia
Peter MacCallum Cancer Centre is 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.
Tapping into the depth and breadth of knowledge and experience offered by the ten partners of the Victorian Comprehensive Cancer Centre (VCCC) alliance, the University of Melbourne’s Comprehensive Cancer PhD Program provides a unique opportunity for multidisciplinary cancer-related PhD candidates to experience clinical and research activities across the alliance.
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. https://www.petermac.org/education/comprehensive-cancer-phd-program
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 2019: Round 1 -31 October 2018; Round 2 - 28 Nov 2018; Round 3 - 20 Feb 2019.