Past Winner
2005 NSERC Doctoral Prize

Patrick Seale

Molecular Biology

McMaster University

Early in his doctoral research at McMaster University, Patrick Seale looked in amazement at the scrawny mice he'd bred. They had little muscle and couldn't regenerate muscle as they aged or after injury. What the mice ultimately lacked, though, was microscopic: the Pax7 gene. It had been removed using gene-knockout technology.

For Dr. Seale, this gene-muscle link was a Eureka! moment, which could one day prove life transforming to thousands of people suffering the muscular effects of degenerative diseases and aging. It could even launch a new and controversial genetic approach to athletic performance enhancement.

"The Pax7 gene had never been implicated in muscle regeneration before. Discovering its critical role was definitely the highlight of the doctoral research and inspired me to continue in academic research," says Dr. Seale, the winner of a 2005 NSERC Doctoral Prize – one of Canada's premier graduate student awards.

Our muscles contain specialized stem cells called satellite cells. When activated by exercise, injury or disease, these satellite cells give rise to the majority of the muscle cells that repair the damaged tissue. However, the genetic and molecular mechanisms for this transformation have remained a mystery.

Dr. Seale began to map this biological terra incognito in 2000 when he identified the Pax7 gene as a marker, or identifier, for these satellite cells. This was quickly followed by the groundbreaking discovery that when the gene was deleted in mice, satellite cells didn't develop – a finding that made the front-cover of Cell magazine.

Now hot on the trail of how muscle cells regenerate, Dr. Seale and his Ph.D. supervisor Dr. Michael Rudnicki subsequently figured out that the Pax7 protein acts as a molecular switch to convert adult stem cells (a more primitive, widely distributed type of stem cell in the body) into muscle satellite cells. This was the first research to identify the role of adult stem cells in muscle repair.

Most intriguing from a clinical perspective, Dr. Seale and a postdoctoral lab colleague revealed that proteins called Wnts could trigger adult stem cells to turn on the Pax7 gene and change into muscle cells.

"Since Wnts can be synthesized and potentially given as a drug, they hold a great deal of therapeutic promise for stimulating muscle regeneration and treating patients with diseases such as Amyotrophic Lateral Sclerosis (ALS) and Duchenne muscular dystrophy," says Dr. Seale, from his lab at the Dana-Farber Cancer Institute in Boston, where he's currently a postdoctoral fellow.

Though he believes clinical applications are a long way off, the discoveries have been enough to help propel Dr. Rudnicki, now at the Ottawa Health Research Institute, to launch the Ottawa-based start-up company StemPath to further the development of stem cell-based therapeutics, including those for muscle regeneration.

And while researchers focus on helping treat diseases, elite athletes might also muscle in on the findings.

"The application of these findings for greater muscle performance in athletes is definitely going to be an issue in the long-term," predicts Dr. Seale.

For now his attention has turned from muscle to fat. At Dana-Farber he's exploring the origins of new fat cells in the development of obesity and Type II diabetes.