Success is in the genes

Another way to look at the heart

You could say that Dr. Michael Czubryt’s passion for science is in the genes – in more ways than one.

His curiosity and love of the lab are deeply entrenched in his DNA, inherited from his father – a former chemist at the University of Manitoba. And today, Michael Czubryt spends his days advancing the understanding of the relationship between genes and heart disease. It’s groundbreaking and fascinating work.
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“I was very interested in how genes worked and how we turned our genes on and off and how that defines, to an extent, who we are and how we behave,” explains Czubryt, Principal Investigator, Molecular Pathophysiology with St. Boniface Hospital Research Centre’s Institute of Cardiovascular Sciences. “I always thought it was very interesting. I like puzzles and it was sort of the ultimate puzzle, how all this works together at the molecular level to govern how we behave, these big complex individuals that we are. There’s a lot going on inside of us and it’s remarkable when we try to break it down.”

Cardiac fibrosis

More specifically, Czubryt’s lab studies a condition called cardiac fibrosis. “We have sort of a protein skeleton in our heart,” he explains. “It’s not a bony skeleton; it’s a very soft, supple skeleton, but it provides extra strength to the heart and helps make sure that our heart can take the pounding that it goes through every day. Our heart will beat 100,000 times a day.”

This protein skeleton is a network of collagen fibres, and you need the right number of fibres for the cardiovascular system to work properly. Having too many fibres interferes with the heart’s ability to do its job; having too few and you lose mechanical strength.

The nature of when and how a person’s body produces these proteins is largely encoded in the person’s genes. Czubryt and his team study the mechanisms that turn genes on and off and how they contribute to heart disease when activated inappropriately.
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“There’s a lot going on inside of us and it’s remarkable when we try to break it down.”

Scleraxis – a breakthrough

It seems that they have unlocked the mystery through a protein regulator known as scleraxis. Czubryt has learned that scleraxis responds to cardiac stress – like a heart attack or high blood pressure – by producing more collagen. As a result, by creating a new form of scleraxis, the team has been able to find ways to prevent excess collagen production. Czubryt first considered the potential of scleraxis when he was on a postdoctoral fellowship in Texas. At that time, all that was really known about scleraxis was that it played a role in the development of tendons.

“Since tendons are full of collagen, the simple idea was perhaps scleraxis has something to do with the formation of collagen, either in tendons or in the heart,” says Czubryt, who continued his research in Manitoba.

“What we’ve found is that, yes, scleraxis is made by the cells of the heart that make collagen. These are called ‘fibroblasts.’ These fibroblasts in disease convert into another cell type called a ‘myofibroblast,’ which is like a really busy fibroblast; it’s like a factory for making collagen. In fact, when that transition occurs, those cells make more scleraxis,” he explains. “Most importantly, we found recently that we can interfere with the function of scleraxis and when we do that, we can shut off the ability of these cells to make collagen, so they stop making it completely. It just goes away. “

Now, Czubryt and company are trying to figure out to what extent they can interfere with scleraxis in a disease situation, to stop heart disease in its tracks. Related to this pursuit is the possible development of a drug that can target scleraxis.

Czubryt says that the future success of this work will depend to a great extent on collaboration. He currently has project partners at institutes in Canada, the United States, Mexico, and Europe.

“The days of a lone scientist working in a lab, doing their own little projects and not talking to anybody else, and keeping their stuff secret because they’re afraid somebody’s going to steal it from them – those days are rapidly vanishing,” he says. “I don’t know anybody who can get by in today’s world without extensive collaboration. It’s just the way science is done now.”

They get it!

The objective of successful lab research is to bring products and therapies to market to help improve the well-being of patients. To make that happen, the wheels of discovery must continue to turn. That takes not only collaboration, but ingenuity, patience, and dollars.

Czubryt’s greatest thrill is discovering new things and having his hypotheses confirmed. Not far behind is when his work makes sense to the community. He tells the story of making a 10-minute presentation about his work to a group of donors.

“A few weeks later I got a phone call from one of the individuals who was in attendance and was very interested in sponsoring my lab,” says Czubryt. “It was very exciting, I told my students and they were thrilled because, as one of my students said, ‘They get it. Somebody gets what we’re doing!’ They were very excited about that.”
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To learn more about Dr. Czubryt’s research visit www.sbrc.ca/czubryt

Dr. Michael Czubryt
Principal Investigator, Molecular Pathophysiology
Institute of Cardiovascular Sciences, St. Boniface Hospital Research
Associate Professor of Physiology, University of Manitoba

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