Eighteen months ago, University of Calgary researcher Paul Kubes had a short conversation with colleagues in the intensive care unit about why so many patients with brain injuries die from infections.
What happened next explains why Dr. Kubes will be named Canada’s health researcher of the year Wednesday at a ceremony in Ottawa.
He immediately began to investigate, using a technique that allows him to see inside blood vessels and track the movement of particular kinds of immune system cells.
He and his team made a discovery that sheds light on how the injured brain suppresses the immune system, published last month in the prestigious journal Science. It could give doctors a new tool to help fight potentially deadly bacterial invasions in people with brain injuries.
“From this simple conversation, a huge finding,” said University of Calgary critical care physician Chip Doig.
The Canadian Institutes of Health Research “Researcher of the Year” prize comes with a $500,000 grant, spread over five years.
Dr. Kubes will use it to continue his research on the immune system, how it saves us from infectious disease and how it can be boosted or tweaked to do better. His novel approach is important at a time when bacteria are becoming increasingly resistant to antibiotics, says the University of Calgary’s dean of medicine Tom Feasby.
Working with mice, Dr. Kubes attaches florescent tags to specific types of immune system cells. He puts the living animals under a spinning disk microscope, which allows him to follow the bright green cells as they travel though blood vessels.
“It is pretty spectacular,” he says.
Dr. Kubes wants to know what happens in sepsis, when bacteria move into the bloodstream with potentially deadly consequences. He is also investigating why the immune system sometimes causes so much damage, why it can turn on healthy tissue after a heart attack, stroke or other brain injuries, and in diseases like multiple sclerosis.
He suspects the key to understanding these diseases is learning more about the body’s wide array of defenders, the different types of cells that play a role in fighting infection.
He wants to know how they behave under different circumstances, like a brain injury.
In the case of stroke, a blood clot or a bleed in the brain damages tissue. But then, the immune system makes the situation worse. White blood cells seem to no longer recognize damaged cells as part of the body, says Dr. Kubes, so they release hydrogen peroxide and other toxins to finish them off.
“They are armed with most toxic molecules that the body makes,” Dr. Kubes says.
To protect itself, the brain suppresses the immune system, Dr. Kubes says. He and his colleagues discovered that immune system cells that hang out in the liver play a key role in dialing the immune system down after a brain injury.
This makes patients more vulnerable to infections. About 10 per cent of stroke patients die, the majority from an infection.
It might be possible to tweak these natural killer T-cells with a drug, to get them to signal to the rest of the immune system that it is time to gear up, says Dr. Kubes. His work suggests that this wouldn’t increase the extent of the brain injury, and he is now investigating if the same mechanism is at work in humans.
Dr. Doig says before the discovery, most intensive care unit physicians would have scoffed about the possibility there was a specific immune system problem in brain-injured patients
“This is a totally new potential mechanism of immune dysfunction, and if the finding can be converted into a potential treatment, it would be extremely important,” he says.