Dr. Duncan Stewart

Evelyn and Rowell Laishley Chair CEO and Scientific Director Ottawa Hospital Research Institute Professor of Medicine, University of Ottawa
Researcher of the month: 
Sep 2010

“As a physician who does fundamental research,” says Dr. Duncan Stewart, CEO and Scientific Director of the Ottawa Hospital Research Institute (OHRI), “I strive to take advances in molecular science and make them relevant for patients.”

Dr. Stewart’s innate curiosity and heart-felt concern for patients with diseases of the heart and lung have led researchers in laboratories at McGill University, St. Michael’s Hospital in Toronto, and the OHRI to achieve important advances in cardiac and pulmonary research. He and his research teams have a long record of world’s first discoveries in vascular biology.

A McGill University graduate in internal medicine and cardiology, Dr. Stewart studied in Germany before returning to McGill to teach, work as a staff cardiologist at Royal Victoria Hospital and establish a vascular biology laboratory. 

“We were first to recognize the importance of endothelin in pulmonary hypertension. We published a series of papers that established that beyond a doubt,” he says. This work provided the impetus for a new class of drugs for pulmonary hypertension: endothelin receptor antagonists.

Dr. Stewart was also first to discover the importance of nitric oxide in stimulating blood vessel growth and protecting tiny blood vessels from injury.

In 1994, he became Head of Cardiology at St. Michael’s Hospital, Toronto. A few years later, he was Director of Cardiology at the University of Toronto. He was awarded the prestigious Dexter Mann Chair of Cardiology in 1999. In 2003, stepped into the job of Associate Research Director at St. Michael’s, and assumed leadership of the Regenerative Medicine Program of the new McLaughlin Center for Molecular Medicine at the University of Toronto. He soon became Executive Director of this centre.

His laboratory at St. Michael’s Hospital was the first in Canada to use human genes to stimulate the growth of new blood vessels to help improve blood flow to the heart of patients with severe and refractory coronary artery disease.  He led several Canada-wide, multicentre trials that are widely cited today.

A few years later, he and his team pushed the boundaries of discovery again by injecting genetically engineered stem cells into diseased lungs to attempt to repair and regenerate new blood vessels. This ongoing program may offer a cure for pulmonary hypertension, a progressive and nearly always lethal condition.

Capital science

Dr. Stewart moved to Ottawa in 2007 because he saw that the OHRI represented a unique environment that was highly focused on translating research into benefits for patients. He was particularly impressed with the clinical trial specialists and infrastructure available to “support people like myself who want to do a rigorous study to address what they believe is an important point or question, and do it in the right way.”

At OHRI, Dr. Stewart continues to work at the forefront of the revolutionary field of regenerative medicine, which seeks to repair and rebuild injured cells in the heart, lungs and other organs by using the body’s building blocks – genes, stem cells, and genetically engineered cells.

Just after his arrival, he played a key role in bringing together researchers from four local research institutions in the Translation of Innovation into Medical Excellence (TIMEx) project. A prestigious grant from the Canada Foundation for Innovation (CFI) funds the $65M health-research project – the largest in Ottawa’s history. It has enabled Ottawa researchers to obtain the highly advanced technical equipment that they need to translate molecular research into practical therapies – to move molecules into medicine.

“Translational research is close to my heart. It’s very hard to do, and you can’t do it on your own. You have to do it as part of a team making a concerted effort, with different scientists and clinicians, pulling together.”

TIMEx offered Ottawa institutions the opportunity “to work to a common purpose,” he says. “It galvanized the community around the idea of translational research. Its success has helped to shine a light on the way forward.”

CFI-funded projects like TIMEx enable scientists to access the equipment they really need “to push their research up to the next level” and allow Canadian researchers to compete internationally, says Dr. Stewart.

New advances

Dr. Stewart’s zest for his work is matched only by his pursuit of the highest standards in clinical research. He is currently leading the world’s first clinical trial of a genetically engineered cell therapy in patients with pulmonary hypertension. The early-phase trial, which focuses on safety, involves a small number of difficult-to-treat patients. The outcome looks promising, he says. Results are expected by year’s end.

Meanwhile, he is in the throes of beginning a similar trial in heart patients with a genetically enhanced cell therapy that aims to repair injured hearts.  

Aha moments

Research is slow business, says Dr. Stewart, but you have moments of insight. Often, major advances come out of left field and not from where they’re expected.

When he first began experiments with cell therapy in the lung, long before stem cell research became mainstream, scientists were starting to study the use of cells as biologic vehicles to deliver gene therapy. Getting genes to their target is one of the main challenges of this research.

As a physician, Dr. Stewart knew that the lungs filter blood at pre-capillary arterioles. Could genetically engineered cells be used to deliver a gene product to that region?

“We began to experiment with them. Usually, nothing works the first time, but things immediately clicked. It was amazing to see how these cells actually home. They go exactly to that region of the lung and stay there. They incorporated into the blood vessels,” he recalls.

“We had a tremendously important and beneficial biologic effect in doing this strategy with genetically engineered cells – much greater than we’d seen using other methods to deliver genes to the heart and other organs.”

Looking forward

Dr. Stewart is convinced that the marriage of molecular science and stem cell research will lead to promising therapies in years to come – perhaps sooner than we imagine.

“I don’t think it will be very long before you’ll see adjunct cell therapy as a commonplace treatment for patients,” he says.

Ms. Jennifer Paterson