Research Profile - See cell. See cell run.
Dr. Paul Kubes
It's like a miniature version of white hats vs. black hats – bacteria (black hats) invades the body, with white blood cells (white hats) in close pursuit. And once they're caught, the black hats are run out of town, with the help of some timely inflammation. But sometimes the white hats get carried away, even when there are no black hats to fight. And that's when inflammation becomes harmful.
Dr. Paul Kubes has a front-row seat at the chase. He's spent the last 10 years developing new imaging technology that lets him watch white blood cells move through the body, pursuing bacteria and expelling it before it causes too much harm. In fact, working with mice, he can watch all the different kinds of white blood cells, including leukocytes, monocytes and neutrophils, as well as the bacteria they're chasing in blood vessels.
At a Glance
Who: Dr. Paul Kubes, Canada Research Chair in Leukocyte Recruitment in Inflammatory Disease; Professor and Director, Calvin, Phoebe and Joan Snyder Institute of Infection, Immunity and Inflammation, University of Calgary.
Issue: When the body experiences infection or injury, the immune system sends out white blood cells, which produce inflammation as part of the healing process. When those white blood cells over-react, though, as in auto-immune disease or stroke, inflammation causes damage.
Approach: Dr. Kubes has developed an imaging system that allows him to watch immune cells, and the bacteria they're chasing, in real time. Knowing just how these cells work means that Dr. Kubes and his colleagues can develop treatments to enhance them where they're needed, and curb them where they cause harm.
Impact: Dr. Kubes' work could lead to the development of new ways to help the body fight infection or injury, as well as to prevent inflammation-linked damage to the body.
"We're the only ones in the world doing this," he says.
But it's not just the thrill of the hunt that intrigues him. He wants to understand how white blood cells produce inflammation in response to injury or infection – and why they often overreact, causing uncontrolled and damaging inflammation. He hopes this new understanding will lead to new ways to intervene – both to encourage and discourage the inflammation, as appropriate.
"Any time you involve the immune system in response to an infection or injury, that's called inflammation," he explains. "It's essential, but it's not so good if it's responding to something in your own body."
Take the H1N1 virus, for instance. It's an incredibly clever bug, Dr. Kubes says. It actively hijacks the immune system by covering white blood cells with platelets, leaving them unable to catch pathogens, whether bacterial or viral. By studying exactly how it manages to do this, Kubes is hoping to open the way for new treatments that can stop the hijacking and enable the immune system to do its work. In the case of a pathogen like H1N1, the inflammation produced by the immune system at work is good.
Something like stroke, however, is a different story. This brain injury happens without any infection at all, but the immune system rushes to the site regardless. Once there, white blood cells get to work destroying injured cells, through inflammation. The problem? Once cells have died, the brain can't develop new, replacement cells. So in this case, you want to figure out how to reduce the inflammation, quickly. The need here is for drugs that can reduce the inflammation without harming the body's ability to fight infection.
And then there's auto-immune disease. In the case of these diseases, which include such familiar diseases as type 1 diabetes and multiple sclerosis, immune cells attack a person's own body. The inflammation that is caused by this attack results in damage to whatever area of the body is affected.
Obviously, it would be a fairly simple matter to simply disable the immune system and stop it attacking where it shouldn't be. But it would be a hollow. The auto-immune disease would be conquered – but the person would be vulnerable to any infection that came along and likely wouldn't live long enough to really enjoy his or her disease-free state.
So success for Dr. Kubes would be developing ways to shut down the immune system's harmful actions, while keeping its protective abilities. By watching the immune system at work, he hopes that what he learns will help reduce the impact of an "over-exuberant" inflammatory response.
The Study
Dr. Paul Kubes has developed an imaging system that lets him watch white blood cells move through the blood vessels of living mice in real time. He is looking at how different white blood cells enter the vasculature, or circulatory system, of the liver to better understand how they are recruited during various inflammatory and infectious conditions.
Dr. Kubes is focusing on the liver because it is designed to use white blood cells to filter and catch disease-causing bacteria and because he believes that the liver is at the heart of any systemic inflammation.
There are at least two types of white blood cells that live in the blood vessels of the liver that can help detect infections and injuries and release factors that initiate inflammation in response. Dr. Kubes and his team have strains of mice in which different white blood cells glow, to help them tell which white blood cells are involved in which recruitment pathways and in which inflammatory conditions. This knowledge may help in developing strategies to reduce an over-exuberant inflammatory response.
"Inflammation is probably killing more people than anything else on earth. If we could find better, more specific drugs to block some of the effects that kill our own bodies without making patients more susceptible to infection, we'd be much better off."