By Tyler Young
“It’s flattering because I’m not eligible for a lot of young investigator awards anymore,” Grande-Allen, 41, said after being presented the award June 15. “But I am really, really proud of it.”
Winning the Durelli Award, which has now been presented five times by the Society for Experimental Mechanics, serves as a prominent acknowledgement of the 20 years of work Grande-Allen has done in heart valve research. An associate professor of bioengineering at Rice University in Houston, Grande-Allen has spent her research in a field that hasn’t received a lot of attention, but her persistence has helped make headway in searching for treatments and cures for heart valve disease.
The four valves in the heart open and close to control blood flow through the heart. When working properly, the valves open to approximately the diameter of a quarter and close tightly to prevent blood from leaking. A valve can develop two kinds of problems: stenosis, when the valve does not open wide enough and only a small amount of blood can pass; and regurgitation, when the valve does not close all the way and blood leaks backward. With both afflictions, the heart has to work much harder to compensate for the erratic blood flow. Approximately 100,000 people each year in the United States undergo heart valve replacement or repair surgery, and many more are estimated to be afflicted with some form of valve disease.
Grande-Allen, who graduated from Transylvania with majors in biology and mathematics, began studying heart valves when she started her Ph.D. research at the University of Washington in Seattle. At the time, the majority of the research being done was focused on improving replacement heart valves instead of the disease itself and possible treatments or cures.
“That kind of stifled study into what causes valve disease because the (replacement valve) surgeons are excellent, and the replacements are awfully good,” Grande-Allen said. “So they weren’t really asking, ‘How can we prevent this disesase in the first place?’”
But Grande-Allen did ask that question. Even though replacement valves have become so effective, the surgery is still invasive—although work is being done to begin widely implanting them in a non-surgical manner with a stent—and finding treatments for valve diseases remains an appealing goal. That’s why she has spent all this time on just that problem.
“We’re trying to improve the range of options for treating people with heart valve disease,” she said. “Some of my work is targeted to helping find new medications so people could just take some pills instead of having to have surgery.”
The work has taken her from Seattle to the Cleveland Clinic in Cleveland, Ohio, for five years, then to Rice in 2003. Her research includes creating complex computer models of the valves that she uses to simulate not only the valve and its function, but diseases, abnormalities, and even surgeries.
She began by working with a tissue bank to get donated human heart valves that were not able to be used in patients. She did magnetic resonance imaging on the valves and was able to learn a lot about the size and geometry of normal valves. She took the results and entered the data into a computer application to render a simulated heart valve.
“For my Ph.D. research, I was creating rather complicated models, and we had to run them on supercomputers, and it still took days and days for them to solve,” she said. “Now you can do it on a laptop.”
She took that rendered valve and was able to simulate numerous factors, including birth defects, diseases, and even surgery.
“I applied blood pressure to the valve within the modeling software and the valve would close and stretch in response to the blood pressure,” she said. “I simulated valve disease, valve surgery, and replacement of the aorta that surrounds the heart valve with different types of artificial blood vessels. It was a really rich project, and we published a lot of papers out of it.”
One of the more common diseases is calcific aortic valve disease, which is when the aortic valve turns into a mineralized, bony structure. The valve does not open and close properly because of the calcification, and blood leaks backward against the normal flow of blood. Often the only symptom a person feels with the disease is tiredness or shortness of breath, but the disease can cause much more serious cardiovascular problems.
“The heart has to work really hard to compensate for having a leaky heart valve,” Grande-Allen said. “There’s not enough oxygenated blood moving forward—much of it is trickling back.”
Most people would have the aortic valve replaced, but Grande-Allen’s research is dedicated to fixing the problem at the source. Some aspects of the disease are similar to atherosclerosis, the disease where blood vessels fill up with plaques and slow blood flow. But similar treatment has not proven to be effective.
“Statins like Lipitor are wonderful for treating atherosclerosis, but they’ve been found to be pretty useless in calcific aortic disease,” Grande-Allen said. “So these diseases are unique enough that they need to be studied on their own, and that’s one of the things we’re doing.”
But progress has been made in searching for other chemicals that will have a comparable effect on valve calcification.
“My students and I have found some neat things,” Grande-Allen said. “We’ve found that certain chemicals will inhibit the calcification of heart valve cells, but these chemicals are also known to be things that would cause other problems if you gave them to patients. So we haven’t found some magic cure drug yet, but we’ve found some novel directions for studying the way cells are behaving.”
Another treatment method Grande-Allen is developing uses living valve replacements that are tissue engineered.
“Tissue engineered valves could actually grow and heal inside the patient, as opposed to an artificial valve,” she said. “We have some promising research in my lab on that, too.”
Grande-Allen works closely with cardiac surgeons and cardiologists along with other bioengineers. Most of her work has been in medical centers, including the University of Washington’s department of cardiothoracic surgery, the Cleveland Clinic, and now Rice University, which is part of the Texas Medical Center in Houston. The Texas Medical Center has 49 institutions and is the largest in the world, and Grande-Allen has collaborators in several of those institutions. One of them, The Methodist Hospital, even appointed her director of heart valve bioengineering.
The recognition she’s gotten has served as an encouragement to continue battling the valve diseases. With as much progress as she’s made—she has published approximately 70 papers and counting—she is able to look fondly on her career so far.
“It’s been fulfilling, especially when I see how many people have read our papers over the years and built upon that work,” she said. “I’ve learned a lot along the way and have worked with some wonderful people.”
One of the people she credits for steering her in the direction she went is Transylvania mathematics professor David Shannon.
“He was my mentor when I was at Transylvania, and he really impressed upon me that I should continue doing something that had a mathematical component,” she said. “So I was attracted to a project I saw on computer modeling of heart valves, and I signed on for that research project. I learned that it was a really compelling problem, and I’ve wanted to keep working on it ever since.”
In fact, several Transylvania professors left an impression on Grande-Allen’s education and career.
“Without question, all of the support I got from my math professors was exceptional,” she said. “I absolutely loved the classes I took from (former mathematics professors) Jim Miller and (the late) David Choate. In biology, I really enjoyed (late professor) J. Hill Hamon’s classes—it was such a lively atmosphere. Even the labs were fun. We studied together, we worked together—I just loved being at Transylvania.”