“We have a long way to go to cure heart disease.” This is the view of Dr. Peter Liu, the recently appointed Scientific Director at the University of Ottawa Heart Institute. Despite the state-of-the-art care available today, doctors are yet to restore a patient’s heart and blood vessels to their original, undamaged state of function following a heart attack, stroke or heart failure.
“How do we provide true healing?” asked Dr. Liu. “When people have a heart attack, they still go home with a scar, and they eventually can end up with heart failure. When people have dangerous heart rhythms, we implant a defibrillator, but it does not cure the underlying problem. Similarly, 70 years after the discovery of insulin, we still don’t know the cause of diabetes. So we’re still dealing with halfway technologies, not truly curative strategies.”
Dr. Liu is a prominent figure in the cardiovascular community, having held leading positions in research and administration, including most recently, Scientific Director of the Institute of Circulatory and Respiratory Health at the Canadian Institutes of Health Research (CIHR). Earlier, he was the Director of the Heart & Stroke/Richard Lewar Centre of Excellence at the University of Toronto.
“When people ask, ‘Where are the next innovations in cardiovascular medicine going to take place?’ I want everyone to look to Ottawa.”– Dr. Peter Liu, Scientific Director, UOHI
In his new role, he will help the Heart Institute manage a research endeavour that has grown rapidly in funding, scope and impact over the past decade. An array of major findings, top-tier publications and recent rankings all reflect a profile that is well-established nationally and increasing internationally.
“The Heart Institute uniquely ‘punches above its weight,’” said Dr. Liu. “People at the Institute have good esprit de corps, share common goals and are very talented. It’s a place where very sophisticated care takes place. I want us to make a serious effort in taking up international leadership in research. When people ask, ‘Where are the next innovations in cardiovascular medicine going to take place?’ I want everyone to look to Ottawa.”
In assembling a new strategic plan for research, Dr. Liu is working closely with the Ottawa region research community for broad input and consultation. The plan will build on existing strengths and successes in areas such as genomic medicine, atherosclerosis, imaging, community prevention programs, and regenerative medicine. In addition, new areas that include heart failure, obesity and metabolic syndrome, inflammation and protein dynamics will receive greater emphasis, as will personalized precision medicine.
To achieve true innovation in research, Dr. Liu encourages collaboration with fields less traditionally associated with cardiovascular medicine, such as nanotechnology, targeted drug delivery, biomarker-based clinical trials and even global health. He cites recent discussions with National Research Council scientists who are creating tiny antibodies designed to carry drugs across cell membranes. Also, Dr. Liu is leading a project funded by CIHR and the World Heart Federation that uses cellphone-based reminder systems to improve high blood pressure control in Canadian aboriginal communities and in countries across Africa.
Although nanotechnology and global health are disparate fields, they include components that could be borrowed and applied effectively to cardiovascular medicine in Canada, he explained. “Innovation comes from within a discipline only very slowly. However, the cross application of ideas and tools from one discipline into another entirely new field can fast-track innovation.”
In addition to his role directing research at the Heart Institute, Dr. Liu is a practicing cardiologist. Early in his career, he did his residency in cardiac imaging and immunology at Massachusetts General Hospital/Harvard Medical School. In fact, he trained there together with another Heart Institute cardiologist,
Dr. Terry Ruddy, who recently stepped down as division chief. As a clinician, Dr. Liu will join the heart failure and imaging teams. “It is important to be out there on the front lines with patients,” he said. “Working with patients informs my research. We can experience first-hand the pressing issues that critically require answers and disease conditions that require new diagnoses and treatments.”
His lab is examining the body’s inflammatory response as a contributor to heart disease. The team uses a mouse model that has its inflammatory response genetically altered in order to explore this connection. “We were surprised to find recently that these little fellows with certain immune switches turned off can have sky-high cholesterol levels from eating a rich Western diet, and their arteries are squeaky clean,” he explained. “It’s not the cholesterol itself that’s most important, but it’s how your body deals with it that’s the major determinant of the health consequences.”
“We’ve been trying to uncover what exactly is a favourable response to high cholesterol and what’s an adverse response,” he added. His team is testing potential vaccines to prevent chronic inflammatory response to cholesterol as well as other triggers of damage in the circulatory system.
But a significant new part of his team’s research is based in the emerging field of proteomics—the large-scale study of the structure and function of proteins and how they drive the inner workings of cells, especially related to heart failure. He sees this work as complementary to the genomic strengths of the Heart Institute. “Once you find the genes that contribute to a disease, you have to know their function. And the proteins produced by those genes are the natural next steps,” said Dr. Liu.
“Proteomics helps us identify novel biomarkers in the blood, in the urine, in the breath, as ways of diagnosing disease and predicting response to treatment. Identified proteins can then be labelled for imaging to track their location and function, and to develop therapeutic targets,” he continued.
“People talk about heart failure in terms of heart cells dying,” Dr. Liu explained. “But we find that protein abnormalities are the major reason that the heart fails.” Since heart cells rarely multiply, they live more than 60 years and can accumulate large errors in their proteins over time.
“Whenever there are injuries to the heart, or when you are stressed, the proteins get modified. When these modified proteins can’t be repaired or recycled, they stick together or block normal protein function. We find that the proteins get very sticky in these older heart cells that have been injured, and then they begin to interfere with the normal function of the cells. They can cause cells to die early,” he said. “People haven’t yet been thinking about heart failure, or heart disease in general, in that way before.”
As the technology for proteomics, nanobiologics, biosensors and new therapeutic tools continues to improve, Dr. Liu expects the coming decade to be a particularly exciting one. “It’s been trial and error in understanding these diseases, but I think we now have tools that we can use to look under the hood and see exactly what’s wrong with the heart and blood vessels. We can now come up with new insights and solutions that we couldn’t even imagine a decade ago.”