Dr. Paul Kubes

I did my graduate work at Queen's University in Kingston Ontario. I tried to understand how the body decides where to send blood when there is a crisis such as a hemorrhage or during hypoxia. Under the guidance of Dr Chris Chapler, I very much developed a passion for science. I became very intrigued that when blood flow was reduced to a tissue (ischaemia) this in itself does not harm the tissue, but when blood is re-introduced to the tissue (reperfusion) horrible injury ensues. I decided to pursue this further by doing a postdoctoral fellowship with Dr Neil Granger a famous Physiologist in the United States (Louisiana State University Medical School). He had discovered that the lack of oxygen was the problem during the low blood flow state and that at the time of reperfusion the oxygen was re-introduced and now used inappropriately to create free oxygen radicals that were responsible for the injury. This was important in the clinical setting as low flow (ischaemia) followed by (reperfusion) is a problem in strokes, heart attacks, transplantations, and various surgical interventions.

I worked on trying to understand what the source of the oxygen free radicals was. I learned to use a technique called intravital microscopy which permitted me to visualize the tiny blood vessels within a tissue. Much to my surprise, following the ischemic episode, at the time of reperfusion I could see many, many white cells sticking within the blood vessels. These white cells turned out to be neutrophils, the most abundant immune cell in the body. In fact we make 100 billion of these cells everyday to continuously fight infection. However, in the case of ischaemia followed by reperfusion, there was no bacterial involvement, which really puzzled us. Interestingly, the neutrophil is probably the largest source of oxygen free radicals and so we hypothesized that somehow during ischaemia/reperfusion, the neutrophils begin to see the post-ischemic tissue as altered and begin to destroy our own tissue.

In 1991, I moved back to Canada because of an opportunity provided by the Alberta Heritage Foundation for Medical Research. This allowed me to start my own laboratory and began to investigate possible mechanisms underlying the inappropriate recruitment of neutrophils into the post-ischemic tissue. We learned what molecules the neutrophils use to grab or adhere to the lining of blood vessels and demonstrated that if you could block that adhesion the neutrophils were not able to cause injury. Clearly getting to the tissue was much of the battle. Many drug companies are trying to design molecules that will reduce the adhesive properties of neutrophils and thereby inhibit their ability to injure. We asked the simple question of why are we not always inflamed and discovered that nitric oxide is a major Teflon for blood vessels keeping neutrophils from adhering and proposed that the use of nitric oxide either as a molecule injected into blood or as an inhalant might greatly reduce the injury caused by neutrophils.

My research program has greatly expanded. I know have many trainees in my laboratory and we investigate many different pathologies in addition to ischaemia/reperfusion. However, the major theme regardless of disease is to observe and understand how the white cells are stopping in the vasculature and injuring tissues. I have had a wonderful opportunity to work with outstanding colleagues and trainees from all over the world. Their enthusiasm continues to make the research very worthwhile.

The work is presently sponsored, primarily, by the Canadian Institutes of Health, as well as the Heart and Stroke Foundation of Canada, the Crohn’s & Colitis Foundation and Bayer. I hold a Canada Research Chair.

For further information, please contact Dr. Paul Kubes using the Email contact form or by phone at 403 220-8558