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Heart for Research

Posted by on Wednesday, April 20, 2011 in Next, Spring 2011.

The windows in David Merryman's office also serve as a whiteboard for ideas and working out formulas.

Talk to people who know David Merryman best, and one adjective is heard frequently: passionate. Talk to Merryman yourself and it is easy to see why.

Discussing his research, the assistant professor of biomedical engineering seems ready to leap out of his chair at any moment, perhaps to tweak the complex formulas written in grease pencil on the windows of his office overlooking Vanderbilt University Medical Center.

Merryman’s energy and enthusiasm is simple: He hopes to bring that similar vitality to people with valvular heart disease. According to the American Heart Association, it affects more than 13 percent of the population ages 75 and older and directly accounts for more than 21,000 deaths each year. Its cause remains unknown.

Merryman’s lab is currently conducting multipronged research into valvular heart disease. One prong focuses on studying the effect of the growth factor, transforming growth factor-beta 1 (TGF-β1), on heart valve disease under a grant from the National Institutes of Health. “It’s like steroids for the cells,” Merryman says. “The cell gets overactive and starts making more protein than it’s supposed to. We’re trying to look at how mechanical forces change the way cells make TGF-β1. If TGF-β1 is the underlying cause, we think we can prevent it with drugs.”

That’s led to additional research that is exploring whether the specific serotonin receptors on heart valve cells can be targeted to prohibit TGF-β1 when necessary. That work, funded by the American Heart Association, is in its early stages, though Merryman terms its potential as exciting.

David is not only fantastically brilliant, but he’s also extremely creative.

—Phil LeDuc
Carnegie Mellon University

Merryman is also working on other, nondrug methods of fighting the disease. He has developed a percutaneous catheter which one day may take the place of open-heart surgery for certain types of heart valve disease. “With most valve disease, the valves become stiff,” Merryman explains. “But with this type, myxomatous mitral valve disease, the valves become floppy and loose.” His invention combines two clinically used catheters: one catheter to freeze and stick to the valve, and a second to deliver radio-frequency energy.

“We’ve patented this technology to use a dual-energy catheter that uses energy centrally released to ablate the tissue,” he says. “The radio frequency energy essentially cooks the valves, like a microwave cooks food, making them stiffer.” Use of the dual-energy catheter would likely be an outpatient procedure, dramatically reducing hospital stays and recovery times for patients by avoiding open-chest surgery.

Bringing Engineering to the Bedside

A Nashville native, Merryman received his undergraduate and master’s degrees from the University of Tennessee. He received his doctorate from the University of Pittsburgh in 2007 and was an assistant professor at the University of Alabama–Birmingham before joining the Vanderbilt faculty in 2009.

“One thing that is impressive about David is No. 1, his enthusiasm and passion for research and questions,” says Dr. Lou Dell’Italia, professor of medicine at the University of Alabama–Birmingham. “His whole personality is infectious. He lights up a room when he comes in. He’s brilliant and loves sharing his knowledge. He’s a wonderful translational scientist bringing engineering to the bedside.”

Doctoral candidate M.K. Sewell-Loftin works on a topographical map, created through atomic force microscopy, of heart valve cells. It’s part of research into how the environment surrounding cells leads to disease conditions.

Merryman says he initially wanted to be a doctor, but disliked organic chemistry. Meeting his future wife during his senior year at the University of Tennessee—she was a junior—kept him in Knoxville for an additional year. He decided to pass the time by pursuing a master’s degree, where his research focused on spine mechanics. He soon turned his interests to heart valves.

“Orthopedics is really focused on reducing pain—and chronic pain is terrible—but it’s not as life-threatening as cardiovascular disease,” he says.

For his doctoral work, he sought out Michael Sacks, the John A. Swanson Endowed Chair in Bioengineering at the University of Pittsburgh, and an expert in heart valve mechanics. “He was at the tissue level and I had done cellular work in the spine. I wanted to do valve cell work and he wanted to start working at the cell level,” Merryman says. “It was nice because we both worked together to start this area.”

Merryman says it casually, but influencing a mentor’s research —especially a world-renowned one such as Sacks—in a new area is unusual. “David is not only fantastically brilliant, but he’s also extremely creative. He took the research of his adviser and really pushed the boundaries of moving down to a smaller scale,” says Phil LeDuc, associate professor of mechanical engineering at Carnegie Mellon University and a member of Merryman’s thesis committee. “It’s a one-in-a-long-time student who is able to comprehend what you’re doing … to push you in new directions is extremely rare.”

Merryman studies multiple approaches to fighting valvular heart disease. “I love the research, the not knowing what is going to happen,” he says.

Energized by the Pursuit

Working with one of the top researchers in the field provided Merryman with a tremendous education. It’s one that he has put to good use, says Harvey Borovetz, chair of the Department of Bioengineering at the University of Pittsburgh. “I could tell from day one, here was someone who was going places,” Borovetz says. “He was trained in a world-class lab and he benefited from that experience and was exposed to so many aspects of regenerative medicine. He was inquisitive and had his own ideas to run with.”

Merryman is also not afraid to take the best of what he learned from mentors and do things his own way. Unlike many labs, the Merryman Mechanobiology Laboratory is family-friendly. Merryman hosts family events, understands when one of his researchers has to be off with a sick child, and encourages taking breaks for a few minutes of Nerf basketball in the lab. “I try to recruit the people who fit into that type of environment,” he says. “I give the students a lot of autonomy and try not to micromanage. … I want the students to own their research. If I have to stay on a student, they’re not the kind of student I want in my lab.”

Merryman and doctoral candidate Steve Boronyak (right) explain how a dual-energy catheter could supplant certain open-heart surgery procedures.

Not micromanaging also allows him time at home with his wife and two daughters, ages 4 and 1. Even at home, though, his mind is constantly thinking.

“I just try to be as efficient as I can when I’m here. At night, sometimes I can’t sleep and I send a bunch of emails. When our youngest was an infant, I would feed her at night. Sometimes I’d be up at 3 a.m. and sending emails. I was up and it was time to think,” Merryman says.

Essentially, he wants students and fellow researchers as dedicated to the work as he is, energized by the pursuit. “I love the research, the not knowing what is going to happen, figuring things out and looking at systems. For the most part, it’s exciting to come to work and say, ‘Today I want to do this,’” he says. “We don’t have a mandate from a board of directors saying that we have to have this product made. Everything is out in the open and anything is possible.”

And anything is possible for the young researcher, as well, LeDuc says. “He’s one of those people who’d like to say he’s on his way to becoming a star. I’d say he’s already there. He’s a tremendous asset,” LeDuc says. “His potential is only beginning to be tapped, not just as a researcher, but as a human being.”