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FISHING FOR CLUES

A small, stripy fish may hold the key to heart and spinal cord regeneration in humans

Growing up in Sendai in northern Japan, Dr Kazu Kikuchi spent all his free time playing in the forest near his home.

“My friends and I used to enjoy fishing and catching crayfish and bright coloured beetles in the forest every afternoon. I was doing very poorly at school. I’d get 10%-40% on exams and I’d throw away the papers on the way home so mum wouldn’t find out. I hated maths!”

At 14, Kazu was the black sheep in a family of high achievers. His father is a surgeon, his mum is an ophthalmologist, even his siblings are doctors.

“It made my mum really upset to see me flunking. She’d say to me ‘I’m not going to be around forever, you need to be able to support yourself’”.

In Japan, students must sit an entrance exam to determine which high school they attend. The brightest children are separated from the not-so-bright and Kazu was destined for the worst school in Sendai.

“I was tiny for my age. The kids at that school were enormous! It would have been dangerous, I would have been constantly bullied and I was determined not to go there! It was almost impossible to catch up. I didn’t even understand what the teachers were talking about in class. But I worked extremely hard.”

 A change of heart

Kazu finished senior school at the top of his class. He graduated from Tohoku University School of Medicine like the rest of his family, but he was rattled by an eerie sense that the next 50 years of his life had already been decided for him. So Dr Kikuchi packed his bags and boarded a plane to North Carolina, pursuing a new adventure as a scientist at Duke University.

For the next five years Kazu was captivated by a surprisingly clever freshwater fish, that can repair its heart, spinal column, kidneys and fins – much like a lizard can grow back its tail.

“Zebrafish, believe it or not, are very similar to humans. Our organs develop in similar ways and almost 70% of our genetic make-up is the same too. If we can understand how zebrafish repair their cardiac muscle, we may get some insight into how we can stimulate healing in the human heart.”

By 2011 Kazu had emerged as a world leader in zebrafish regeneration. He boarded another plane, this time for Sydney, Australia and the Victor Chang Institute.

The first thing you notice when you enter the zebrafish aquarium at the Victor Chang Institute are the blue tanks. There are thousands of them bubbling away, stacked on racks from floor to ceiling. While several scientists utilise the facility, Kazu dominates the space. He’s in charge of approximately 35,000 zebrafish and there are more being delivered from Queensland today. (They fly Virgin Airlines, in a temperature and pressure-controlled cabin).

Every afternoon Kazu can be found in the aquarium discussing progress with his team of researchers.

“He always checks to make sure everything is in place,” says the aquarium’s manager, Cecilia Jenkins. “It’s amazing how he keeps track of things with so many zebrafish to remember, but he is incredibly thorough and notices even the smallest change. He never misses a trick.”

Dr Kikuchi’s research is painfully time consuming and meticulous. But according to his colleagues, when he makes a discovery it has far greater resonance.

Making an impact

His latest scientific paper is the cover story in the highly prestigious journal, ‘Developmental Cell’. The front page features a striking photo, taken by Kazu, of a zebrafish under a microscope. It looks like an X-ray, covered in tiny fluorescent red dots.

There’s a lot of excitement about these bright dots. They’re a special population of immune cells, known as regulatory T cells, which are critical for repairing damaged tissue. It was previously believed that they did not exist in zebrafish. Kazu proved the world wrong.

“One afternoon I received a phone call from one of my technicians who told me to come downstairs quickly. I ran all the way to the aquarium and looked into the microscope and there they were, unmistakably! Hundreds of T cells, sprinkled across the surface of the skin. It was incredibly exciting, we’d never seen anything like it.”

Kazu also unearthed that when a zebrafish is injured, these unique cells migrate to the damaged site and completely regenerate the tissue without any scarring.

“We were fascinated to discovered how adaptable these immune cells are. They have the remarkable ability to change their function and produce regenerative factors specific to the injured tissue. So if the heart needs repairing, they’ll adapt to the heart, or if the spinal cord needs healing they’ll change to suit the spine, and so forth.”

 “Imagine if we could do that in humans!” Kazu exclaims. “If we can manipulate human T cells to cure heart disease, reverse spinal cord damage and repair vision loss the implications are likely to be huge. We just need to keep working at it, no matter how long it takes.”

Even today you can still see glimpses of Kazu as a 14-year-old student. His determination to succeed hasn’t dwindled in all these years.

 

Donate to heart research


Driving our discoveries

At the end of 2016, Dr Kazu Kikuchi was awarded a three-year Project Grant from the National Health and Medical Research Council. He has also been honoured with a JDRF Innovation Award for his promising investigations into zebrafish immune cells and type 1 diabetes. This funding is integral to the ongoing success of the research program at the Victor Chang Institute.

Make a difference

A gift in support of Dr Kikuchi’s research will:

  • Enable significant medical findings in regenerative medicine with far-reaching community impact
  • Aid in the development of molecules that stimulate growth of new cells in a damaged human heart, spinal cord and retina, helping them function again after serious trauma
  • Potentially reverse our understanding that a human heart, spinal cord and retina lack the capacity to regenerate muscle cells 


Cardiac Regeneration Laboratory

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