Teo Research Fellowship « Charlie Teo Foundation

Space Biology to Treat Brain Cancer

Researcher name: Dr Joshua Chou
Institution: University of Technology, AUS
Grant name: Teo Research Fellowship
Grant amount: $200K
Grant years: 2020-2022

Meet the Researcher

Dr Joshua Chou is the epitome of an unconventional researcher. Inspired by the world’s most famous theoretical physicist and cosmologist, Professor Stephen Hawking, who provided personal advice to Joshua “that nothing defies gravity”, Joshua has applied his learnings from Harvard to use space biology to disable some of the hardest cancers to fight, like brain cancer.   

Never before has space biology been applied to brain cancer research. The team’s previous work has shown that other cancer cells at micro-gravity are unable to sense each other, no longer grow into tumours and die. The project will go a step further and in an Australian first, a research mission will launch brain cancer cells into space to orbit on the International Space Station to see if brain cancer cells can be killed at zero gravity and understand how that is happening.

While eventually brain cancer patients may be sent to space for treatment, the outcome is to develop drugs that patients can take while on Earth that tricks the brain cancer cells into behaving like they are in space.

Space microgravity to disrupt GBM mechanotransduction

Mechanobiology is the study of how cells are influenced by their physical environment. This emerging field of research provides an important perspective on understanding many aspects of cellular function and dysfunction.

Gravitational force is presumed to play a crucial role in regulating cell and tissue homeostasis by inducing mechanical stresses experienced at the cellular level. Thus, the concept of mechanical unloading (a decrease in mechanical stress) is associated with the weightlessness of space and can be replicated by simulating microgravity conditions, allowing for investigation of the mechanobiology aspects of cell function. The mechanical unloading of cells under microgravity conditions shifts the balance between physiology and pathophysiology, accelerating the progression and development of some disease states.

Cancer cells subjected to very weak gravity (microgravity) have been shown to have an altered cell cycle as well as a decreased migratory response. As such, microgravity has been thought to have anti-tumour potential through growth inhibition.

Previous groups have shown that microgravity inhibits proliferation and increases the chemosensitivity to cisplatin of malignant glioma. Thus, by subjecting glial tumour cells to microgravity, this project aims to further characterise the underlying fundamental molecular mechanisms that determine the aggressiveness of high-grade gliomas and identify novel therapeutic targets that are critical drivers of glioblastoma growth, highlighting a new direction and era for brain cancer therapies.

The Cancer Clock is (not) Ticking

Researcher name: Dr Kristina Cook
Institution: University of Sydney, AUS
Grant name: Teo Research Fellowship
Grant amount: $200K
Grant years: 2020-2022

Meet the Researcher

Dr Kristina Cook is an up and comer cancer researcher who fought her own battle with a rare tumour. She studied at Oxford and the National Institutes of Health (NIH) where she has collaborated and published with leaders in the cancer field, including 2019 Nobel Prize winner in Medicine, Professor Peter Ratcliffe.

The power of the circadian rhythm in controlling how the body functions is just being understood. For example, it was only in 2017 that the Nobel Prize in Physiology went to scientists finding what controls the circadian rhythm. Now, only a few years later, we’re already taking this knowledge and seeing whether it’s the missing link in understanding why targeted treatments are not working in brain cancer.

Brain cancer is one of the best genetically mapped cancers but despite this, treatments targeting specific genes of the cancer have not worked. Perhaps it is not the failure of the treatments but the failure to give the treatments at the right time of day, where it will have the most impact and stop the cancer in its tracks.

The cancer clock is (not) ticking: how brain tumour hypoxia regulates circadian rhythms

Circadian rhythms are physiological, behavioural and cellular changes that follow a daily 24-hour cycle. These rhythms are encoded as a ‘molecular clock’ in the genome of nearly every cell of the body. Individual cells in the body are normally synchronised to the external time by a ‘master clock’ present in the suprachiasmatic nucleus of the brain. Clinical and laboratory-based studies have suggested links between disrupted cellular circadian clocks and brain tumour progression, but the mechanisms are poorly understood. It is vital that we understand how circadian rhythms affect brain tumour growth and progression, as they may be a novel anti-cancer strategy.

One proposed mechanism of circadian control is through tumour hypoxia (low oxygen). Hypoxia is common in high-grade brain tumours, particularly glioblastoma, due to rapid cell proliferation. Both hypoxia and circadian disruption are associated with aggressive behaviour in brain tumours. Furthermore, hypoxia can ‘reset’ circadian rhythms and tumours may use this to control circadian and oncogenic pathways.

This project aims to understand how hypoxia can alter circadian rhythms to increase brain tumour progression, with the goal of identifying whether the circadian rhythm can be used to synchronise brain cancer cells to a time of day where they are most vulnerable to attack through new drug targets.