Walk down a long hallway packed with rows of sample-chilling refrigerators, open the door to a bustling, sunshine-filled laboratory, and examine a larger-than-life model of David Merryman’s inspiration, sitting on the counter nearest the door.
It’s the human heart.
The organ has filled Merryman’s days – and those of his graduate students – since he arrived at Vanderbilt University six years ago. He’s scribbled formulas about it from top to bottom on an expanse of windows. Pictures placed around his office provide a look at Merryman’s own heart: His wife, Erin, and three children, who are his inspiration to work so diligently addressing problems with this life-sustaining pump.
“Two of our children had short hospital stays unrelated to cardiac problems,” Merryman said. “I can’t imagine having children in the NICU for heart complications. It’s something that I’m thankful I haven’t had to deal with personally and that motivates me professionally.”
His efforts have not only earned him national recognition for his research but also another R01 grant from the National Institutes of Health and — as of August — the title of associate professor of biomedical engineering with tenure.
The new grant, which should begin in July, will help him continue research on treatment for mitral valve prolapse. It’s a growing concern because heart valve disease is the nation’s third-most common cardiovascular disease and is more prevalent in our aging population.
Traditional treatment for this disease is open-chest surgery and replacement of faulty valves with healthy ones from pig hearts. Merryman’s research suggests a more effective, less invasive approach would be running a catheter through the femoral artery, using a cryogenic freeze to hold the faulty valve into place, then ablating it with radiofrequency energy. The new grant will help his team find the best ultrasound imaging strategy to monitor the process.
Also among his newer projects: one that could reinvent treatment of heart valve disease in children.
Merryman is working with Scott Baldwin, chief of pediatric cardiology at Monroe Carell Jr. Children’s Hospital at Vanderbilt, on developing heart valves using inducible pluripotent stem cells – fully differentiated cells, such as skin cells, that can be reprogrammed to act like embryonic stem cells.
Pediatric heart specialists have been stymied in addressing birth defects and other problems in children’s heart valves because adult treatments don’t work well.
“Kids grow so fast, their hearts outgrow the pig valves,” Merryman said. “It’s really the only option, so we give them a pig valve, then we wait as long as we can – and by then the patients are really doing poorly — and then we replace it with another pig valve that’s too big for them, and they grow into that one. It’s not ideal.”
The best option would be a tissue engineered heart valve that would grow with the patient’s heart. However, the cells of the heart valve are unique and need to be coaxed into their specialized qualities in the laboratory before developing the valve. This is what Merryman and Baldwin hypothesize inducible pluripotent stem cells can do.
Merryman published preliminary work on the project in 2014 after a three-year study of valves in the embryos of chickens, an animal whose heart development mimics that of humans.
Merryman’s path to his current work included bachelor’s and master’s degrees in engineering science from the University of Tennessee. He earned his Ph.D. in bioengineering from the University of Pittsburgh in 2007 and immediately went to work on the faculty at the University of Alabama in Birmingham.
Vanderbilt recruited him in 2009 with the commitment of both lab space in the medical center and of collaborations to help him pursue his research passions. Working in an interdisciplinary area with top Ph.D.s and physicians and surrounded by cardiopulmonary labs is inspiring, Merryman said.
“The heart is among the most mechanical organs. It’s a pump and valves and tubes – as a mechanical engineer by training, those were the things that interested me,” he said. “In graduate school, I focused on molecular biology and wanted to do more work in that area. I’ve been fortunate that I’ve been able to tailor the lab to do exactly what I want, and that the stuff I’m really interested in is what has attracted funding.”
He’s quick to give credit to his large team – both current and previous members. Those include nine Ph.D. students, two M.S. students, a dozen undergraduate students, three research associates and a research assistant professor. Within that list are National Science Foundation graduate research fellows and five American Heart Association pre-doctoral fellows.
Merryman keeps them busy with a host of projects. His other R01 grant supports research into stopping calcific aortic valve disease by targeting serotonin receptors in the heart. His National Science Foundation CAREER Award funds research exploring changes in cell biology due to mechanical stretching – finding new ways to mimic growth, injury and disease in fibroblasts while assessing their shape and structure.
His team is exploring other areas, as well.
“We started out as all heart valve, but we’ve worked our way into doing research on myocardial infarction and pulmonary hypertension,” he said.
Among their new work – looking at a post-heart attack drug that will prevent future heart failures by targeting a specific protein, cadherin-11. He’s also collaborating with James West, associate professor of medicine, on using an old drug in a new way to treat pulmonary hypertension.
Contact
Heidi Hall, 615-322-6614
heidi.hall@vanderbilt.edu
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