Aggressive brain tumours, including adult glioblastomas and pediatric DIPGs, are difficult to treat. Survival rates have improved very little over the last 30 years indicating a need for new ways of treating these tumours. To develop new treatments, a better understanding of the underlying biology is required and this project will investigate cellular pathways known to contribute to brain tumour aggression, including oxygen sensing pathways and circadian rhythms.
Low oxygen environments are a hallmark of grade 4 brain tumours. Hypoxia (low oxygen) leads to oncogenic changes in cellular metabolism, metastasis and chemo- and radio-resistance. These changes are largely coordinated by a transcription factor known as Hypoxia Inducible Factor (HIF), which is activated by low oxygen levels. In animal models, hypoxia can reset or disrupt molecular circadian rhythms by activating HIF. Tumour cells often have disrupted circadian rhythms, and animal studies have shown that circadian transcription factors enhance proliferation and survival in glioblastoma stem cells. Very little is known about how HIF and the regulatory components of circadian rhythms might interact in tumours and this project will investigate and identify new regulatory links.
This project is highly collaborative and will be jointly supervised by Dr Eric Hau and Dr Han Shen.
Techniques include immunohistochemistry, western blotting, qRT-PCR, RNASeq, and various in vivo and in vitro techniques.
The opportunity ID for this research opportunity is 2901