Metabolic rewiring in liver cancer: Role of oxidative stress and the Nrf2 pathway

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, we currently have research projects that aim to 1) Generate a gain of function Nrf2 mutant (Nrf2D29H), frequently recovered in cancer, and characterize the effect the mutation has on metabolic reprogramming. 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 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.
https://www.petermac.org/education/research-education

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.
https://www.petermac.org/education/comprehensive-cancer-phd-program