Smooth muscle researcher William Cole strives to reveal molecular mysteries behind disease

The forests, lakes and the network of tributaries in Ontario’s Muskoka region are well known for their tranquility and beauty. But for William Cole, PhD, they sparked his curiosity in natural history and science during his formative years.
Now a well-established Professor of Physiology and Pharmacology at the University of Calgary, he is an integral part of the Libin Cardiovascular Institute of Alberta’s internationally renowned team of smooth muscle researchers. Cole has been the Andrew Family Professor in Cardiovascular Research since 2005.
Ever since he came to Calgary in 1993, his research focus has been on a different type of tributary network—the vascular network within the body. Cole strives to understand the molecular underpinnings behind the Bayliss effect (the response of vascular smooth muscles to contract upon mechanical stimulation), in hopes that it may unravel the mysteries behind some of the most widespread diseases plaguing humankind today.

Actin stain (phalloidin) rat middle cerebral artery pressurized to 80 mm Hg (contracted)

Actin Stain (phalloidin) rat middle cerebral artery pressurized to 10 mm Hg (relaxed)

“When pressure increases within a blood vessel, the response of that vessel is somewhat counterintuitive,” says Cole. “It actually contracts instead of dilating and in doing so, attempts to control the flow of blood going to the smaller branches of the arterial network.

“This response is of critical importance. It is precisely the failing of this response in later stagesof renal disease and Type-2 diabetes resulting in less controlled flow to delicate glomerulus structures in the kidney and micro-vascular structures in the brain that can result in damage to these critical organs.”
According to the World Health Organization, hypertension is a leading cause of death globally. Cole’s work is directly significant in dealing with high blood pressure because in his words, what he’s looking for are “the sniper bullets to replace the current ‘shotguns’ in the health-care system’s arsenal.”

Molecular level research can pinpoint and help address certain mysteries behind these diseases. To this end, the Cole laboratory has been focusing on voltage-gated and adenosine triphosphate (ATP) – sensitive potassium channel types; transient-receptor potential non-selective cation channel types, and the regulation of the contractile proteins of vascular smooth muscle cells. These are all elements at the core of constriction and dilation-triggering mechanisms in blood vessels.
Financial support from the Andrew Family Professorship and the Kertland Family Fund plays an important part in the success of Cole’s team, as over the years it has contributed to the costs associated with having graduate students. His lab is a beehive of well-choreographed activity.

Bill Cole (left) with Dr. Chukweumeka Nwokocha, a visiting Professor from The University of the West Indies in Mona, Jamaica.

PhD student Zoe Zhong and summer student Dylan Cole with Bill Cole, PhD, in his lab.

This summer, there are three visiting scientists (two from Spain and one from Jamaica), three graduate students, three post-doctoral students, two summer students and a lab technician.
“Our students represent our future,” says Cole.

 

“Coupled with mentorship and training, it is the students’ work which has resulted in some of the biggest breakthroughs we’ve had.”

One such breakthrough in the Cole lab was led by former PhD student Roslyn Johnson. She published work that detailed a new method for studying protein phosphorylation, in effect, a way to study mechanisms behind signaling cascades in very small vessels. Johnson’s training at the Libin Institute allowed her to then pursue a fellowship at Harvard University and onto San Diego, where she currently lives. Today, graduates from the Cole laboratory can be found internationally, from Argentina and the United Kingdom to Japan and Switzerland.
Former CEO and chairman at Ford Philip Caldwell once said, “Successes have many fathers, failures have none.” In the spirit of those words, William Cole with his colleagues, students, staff and supporters such as the Andrew and Kertland families, has and continues to find success.

By Al-Karim Walli

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