Waking up brain stem cells at the right time could one day improve cognition and fight neurodegenerative diseases and cancer, according to Dr Lachlan Harris, a researcher at QIMR Berghofer in Brisbane
Right now, most of the stem cells in your brain have been hibernating for months or years. Without periods of this sleep-like state, known as ‘quiescence’, they get exhausted and die.
Lachlan has discovered the molecular mechanisms that control how healthy brain stem cells fall asleep and how they decide when to wake up.
Now, with the help of one of two $60,000 Metcalf Prizes from the National Stem Cell Foundation of Australia, he’s turning his attention to recurrent – and often lethal – brain cancer.
“It turns out that this same process of sleep is adopted by brain cancer stem cells,” says Lachlan. “They’re able to use this dormancy to survive chemotherapy and radiation therapy. After treatment, these cancer sleeper cells can wake up, leading to cancer recurrence.”
Lachlan and his team’s work unravelling brain stem cell quiescence is fundamental research that could one day be applied to keeping the brain healthier as we age and also to future brain cancer treatments.
“If our ideas are right, it could lead to a whole new way of treating brain cancer, but that’s at least 10 years away,” he says.
Every year more than 1,000 Australians are diagnosed with high-grade glioma, known as glioblastoma, the most common primary brain tumour in adults. Only 5 per cent of people survive 5 years post diagnosis.
Lachlan first studied healthy brain stem cell quiescence during his postdoctoral work at The Francis Crick Institute in the United Kingdom, with much of this work continuing and expanding in his lab at QIMR Berghofer.
“We’ve discovered how cells move between different states of deep and shallow sleep and activity,” Lachlan says. “This process is critical for these stem cells to persist throughout our lives.”
When this sleep process isn’t working properly, it contributes to diseases like Alzheimer’s and Parkinson’s. But other researchers had discovered that brain cancer cells can also enter similar sleep-like states to evade treatment – and that caught Lachlan’s attention.
“Glioma brain cancer cells can adopt sleep-like states to hibernate through treatment, then wake up – which helps explain why the disease almost always returns, even after surgery, chemotherapy and radiotherapy,” he says.
“I realised that as neuroscientists, we have a really good understanding of how this process is controlled in healthy brain stem cells, at least in animals. What if we applied that knowledge to brain cancer?”
While most brain cancer researchers recognised sleeping cancer stem cells as a mechanism of treatment resistance, they were trying to find new ways to directly kill those cells. Lachlan had a different idea.
“I thought, what if we could wake them up first to sensitise them to treatment? It’s a slightly crazy idea, but in brain cancer, very few things work. We need completely new approaches.”
He moved back to Queensland and founded the Cancer Neuroscience lab at QIMR Berghofer, Australia’s first lab studying quiescent glioma stem cells from a neuroscience perspective.
His team has discovered that some brain cancer stem cells exist in an ‘almost awake’ state, making them primed for rapid reactivation – findings that could one day open up new therapeutic strategies.
The Metcalf Prize will help Lachlan pursue his aim of fundamentally changing how we understand stem cell dormancy and brain plasticity and how we design therapies for brain cancer.
He’s thrilled to be a winner.
“Science is really hard, and projects take years to complete,” he says. “It’s lovely to have recognition from your peers and encouragement that we’re on the right path.
“We want to help patients, ultimately. I’m really passionate about that.”
Brain cancer facts
Brain cancer is deadly. Survival rates are low:
- 5-year survival rate of prostate cancer has increased from 60% to over 90%
- Breast cancer survival has increased 72% to over 90%
- The 5-year survival rate for brain cancer has increased from 21.2% in 1986, to only 22.3%
For glioblastoma – the most common primary brain cancer in adults – only 5% of people survive 5-years post diagnosis.
Glioblastoma, a high-grade glioma, is the most common primary brain tumour in adults with a median survival of just 14.6 months from diagnosis.
Every year more than 1,000 Australians are diagnosed with glioblastoma and almost all experience recurrence within two years. Preventing recurrence is therefore the most urgent unmet need in glioblastoma care.
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