“Heart failure is an epidemic and it’s on the rise,” says the cardiologist. “There are about 50,000 new cases a year in Canada, and a million Canadians have it. It’s just as common in women as in men as women get older.”
In her lab, on the third floor of the Max Bell Research Centre, affiliated with the PMCC, Dr. Billia and her team are intent on reversing heart failure. They are seeking to turn the almost impossible into the possible, coaxing the heart to heal itself with genetic reprogramming.
Having worked on a postdoctoral fellowship with cancer researcher Dr. Tak Mak at the Princess Margaret Cancer Centre after completing medical school and specializing in cardiology, Dr. Billia recognized “a lot of genomic similarities between cancer and heart failure.”
Untangling the spider’s web of genes implicated in both diseases led to Dr. Billia’s elegant and potentially game-changing hypothesis.
“I started thinking about tumour suppressor genes,” explains Dr. Billia, “especially the master regulator: p53. When it mutates, it’s one of those permissive signals that allows cancer cells to divide. I wondered what would happen if you knocked it out, just in the heart.”
Would permitting heart muscle cells to divide create new healthy cells that could compensate for damaged ones? She tested the theory on mice, knocking out p53 and one of its master regulators from their hearts. “The result,” she says, “was astounding.”
What she found was that, when the genes were knocked out in the mice’s hearts, the mice died within 10 days.
“Looking into the microscope, I could see that the cardiomyocytes” – the heart muscle cells – “were tiny. ‘Could this be happening because they were dividing?’” she wondered.
The mice were dying because “when you let the whole heart proliferate, it fails,” she explains.
“So the next step was, ‘How do we target this at a site of injury?’ You may still have damage, but you get surrounding cells to regenerate and compensate.”
Dr. Billia acknowledges that her approach to healing hearts through regeneration is different than the path being followed by most heart research colleagues.
They’re trying to grow stem cells into heart cells to replace those that have been damaged.
“There’s a lot of work being done on that around the world,” explains Dr. Billia, “but there are a lot of questions about what cell to use, how to deliver it, what’s the best timing and for what condition.”
What Dr. Billia is attempting, she says, “is more complex. We’re tweaking the genome, getting rid of the roadblock, the p53 gene pathway.”
There are a lot of downstream targets in her sights: other proteins that interact with the p53, other tumour suppressors, injury models and then, the Holy Grail, localized regeneration in the heart and other organs, including the lungs and kidneys, that were long thought to be resistant to regeneration.
But when asked about the biggest challenge she faces in her work, Dr. Billia doesn’t hesitate.
“Money,” she replies.
The funding she’s received so far, mainly from the Canadian Institutes of Health Research and the Canadian Cardiovascular Society, has allowed her to establish her own lab bearing her name.
“I’ve had great mentorship,” she says, giving credit to both Dr. Tak Mak and to PMCC cardiologist Dr. Heather Ross. “I have a grant. And we’re getting past some of the conventional thinking to get to the next great leap. It’s not that the ideas aren’t there and the know-how – it’s the money to get the work done.”
Having her own lab – her name is prominently displayed – is a significant achievement, physical evidence of the Canadian research establishment’s confidence in the woman, the scientist, the potential and the commitment.
She’s especially proud of her team, six women, including a summer student, and the feeling is mutual.
Technician Daniela Grothe has worked with Dr. Billia since they were together in Dr. Tak Mak’s lab at Princess Margaret.
“If she wants something, she works hard for it,” says Ms. Grothe, about Dr. Billia. “She works her ass off. We worked six years to set this up. This lab was a dream. Now a lot of our ideas are coming to fruition,” says Ms. Grothe, who adds: “Most people who have labs, that’s their only job. Phyllis is always a doctor at the same time. She’s 100 per cent research scientist and 100 per cent doctor. There’s never anything lacking on either end.”
“My patients are used to seeing me in jeans,” says Dr. Billia. “They know I’m running back and forth between the lab and the clinic.”
And there could be no greater motivation for commitment and success in the lab than seeing her clinic patients suffer from heart failure.
“My gut says it will work,” she says about the genomic approach to healing hearts. “You can never be 100 per cent positive about research, but what we’re finding is quite striking.”
The next step is testing in larger animals and developing what is known as “preclinical proof of concept.” Pressed for a timeline, Dr. Billia predicts that in five to 10 years, genomic research will result in the heart repairing itself. Genes, she believes, are the key to heart failure.
“We’re trying to understand, at the molecular level, the cascade of events that lead to the heart muscle failing. But we’re just at the tip of understanding every pathway and exactly why the heart fails and why some people recover and some don’t. There are so many unanswered questions.”
The heart, she suggests, for all that it is part of us, is as mysterious to us as the solar system.
One of the unknowns, Dr. Billia explains, is that, while there may be a genetic predisposition to developing heart disease, it’s not clear whether improved lifestyle at an early age can prevent onset of the disease.
But no matter what our genes dictate, she says, “we can improve longevity and quality of life. There are things that you can do.”
If you do only one thing, it’s to stop smoking, she advises.
Dr. Billia is her own example for lowering risks of disease that can lead to heart failure.
“I decided not to get diabetes,” she says.
Because “diabetes is thought to be polygenic” – that is, caused by more than one gene, and it runs in her family – she made up her mind to lose 50 pounds when she turned 50 this year.
She walked at a fast pace on the treadmill at home for 55 minutes most days at maximum incline while watching episodes of Game of Thrones, limited her calories to 1,000 per day on days when she didn’t exercise and lost the 50 pounds in six months.
“I feel better, sleep better and stopped snoring,” she says.
She reads a lot to relax – Robert Sanderson is a new favourite author. “I read every night before I go to bed,” she says. “It helps me shut down at night. It’s a necessary part of my routine.”
She has a small, close group of friends – “a ladies’ club. We meet once a month and catch up. I’m the only physician.”
But she also admits to waking up in the middle of the night and thinking about work – “because the work is so exciting. We have a lot on the go. You worry about keeping it all going.”
Asked whether she worries that her research will bring the results she’s looking for, she replies, “We’ll make it work somehow.” Who could possibly doubt it?
