Success is in the Genes

Advancing our understanding of genes and the health of cells

For Dr. Lorrie Kirshenbaum, medical research is part art, part instinct, and a great deal of hard work. He credits his success, in part, to his upbringing.

“My parents were insistent that we all do well in school, that we had a good work ethic, and good moral values,” says Dr. Kirshenbaum, Principal Investigator, Cardiac Gene Biology, Institute of Cardiovascular Sciences at St. Boniface Hospital. “And I was always hard-working and committed to what I set my mind to do”

He was always motivated by his family and always interested in medicine and understanding “how the heart worked” – more so as he witnessed the demise of his beloved grandparents. But his curiosity about research didn’t really take hold until a transformational summer job between high school graduation and his first year of university – and the start of special relationship with an important mentor.

“It sounds very simple, but 20 years ago this was like science fiction.”

“Dr. Harvey Weisman was a professor at the medical school for 38 years and gave me that opportunity and first exposure to medical research as a summer student,” says Dr. Kirshenbaum. “He really took me under his wing. I was quite taken by that as I hadn’t really known him. He was an older gentleman, older even than my parents were, and yet we got along famously. To this day we have lunch at least once a week, and I have him on some of my research papers. The relationship is really quite important for me because I’m putting back into the system by training others, largely because of the opportunity that was given to me.”

Dr. Weisman was the first of several medical mentors in Winnipeg; at Baylor College of Medicine in Houston, Texas; and Albert Einstein College of Medicine, New York, who were instrumental in Dr. Kirshenbaum’s career. And Dr. Kirshenbaum tries to pay it forward by leading a dynamic, multicultural, energized lab. “My mentors, including the late Dr. Arnold Greenberg, have inspired me to do great things and think outside the box.” Others included Drs. Daniel Sitar and Pawan Signal who Dr. Kirshenbaum continues to work with today. “I think that if you are influenced positively by someone inspiring, you can only want to do that for other people,” he says.

For example, some years ago while guest-speaking at Garden City Collegiate, his alma mater, his former teacher pointed out a particularly keen science student and suggested that Dr. Kirshenbaum give her some work in his lab. She was but very bright and was not sure of a career path. Fast forward about 20 years, and that student is now a successful practising doctor in Winnipeg.

The results of Dr. Kirshenbaum’s leadership style and the influences on his career speak for themselves as his lab has made important strides in understanding genetic influences on the heart. The goal is to find a way to treat heart failure – which affects 500,000 Canadians – by “turning off” a particular gene, or preventing it from turning on in the first place.

“We’re born with a certain number of heart muscle cells – and they have to last us a lifetime,” explains Dr. Kirshenbaum. “Once the heart cells are damaged or destroyed because of disease conditions, following heart attack the ability of the heart to pump blood is also impaired. As a result, a person will develop heart failure.”

While at Baylor College of Medicine, Dr. Kirshenbaum started asking the question: “Could you use a gene to reprogram hearts to be more resistant to heart attack… so people would live longer?” He continued asking this question when he returned to Winnipeg and was able, in his lab, to discover a gene that “switches on” and programs heart cells to die during a heart attack. He describes it as a “eureka moment” that led to further discovery.

The next question Dr. Kirshenbaum asked was: “Why are these heart cells dying in the first place?”

“We know that there are genes that keep cells alive and genes that program or tell the cells when to die. Are these genes activated when a person is having a heart attack?,” he says. “It sounds very simple, but 20 years ago this was science fiction.”

With the knowledge that has emerged over time, Dr. Kirshenbaum and his colleagues have established important therapeutic targets: (1) keeping heart cells alive to prevent heart failure; and (2) preventing this “suicide” death gene from turning on in the first place.

While initially focused on the heart, the work has important implications for cancer treatment as well.

“What’s a cancer cell? A cell that has lost its ability to stop dividing, it grows and grows without dying,” he explains. “So we looked in cancer cells and sure enough, this very gene that should be turned on is not turned on.” Dr. Kirshenbaum believes that through gene therapy, cancer cells can be reprogrammed to stop growing.

Through the evolutionary process, certain genes evolved to protect the body from diseases such as cancer, but people typically didn’t live long enough to get cancer because they died from other causes. Today, people live longer, but the quality of life isn’t always there because the body’s ability to fight cancer and other diseases such as diabetes and hypertension declines as we age. For Dr. Kirshenbaum and his colleagues, the goal is to challenge what’s evolutionary with what’s revolutionary. Research takes time, but the results can be spectacular.

“This is just art. I’m a painter, I’m a sculptor, and I’m an artist. Science and medicine are really the language. We have to come up with creative ideas,” says Dr. Kirshenbaum. “I fondly recall my grandmother once asking me: ‘Well, how do you know what to do?’ Hasn’t this been done before?’ ‘No,’ I said. ‘That’s why we do research… to figure things out… it’s all new.’”

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