During cardiac hypertrophy, the muscle cells of the heart swell in size. This cell growth and the muscle thickening that results can happen in response to stress on the heart — such as a heart attack or hypertension, said Taylor Eggertsen, a biomedical engineering doctoral student at the University of Virginia School of Engineering and Applied Science. As the heart remodels itself in this way, it demands more and more from the body.
“This change in size and shape is just not sustainable in the long run,” Eggertsen said.
Although cardiac hypertrophy is a leading predictor of heart failure, few therapies use drugs to prevent heart failure by targeting cardiac hypertrophy. One reason is because the complex intracellular signaling network that controls this process has been difficult to untangle, Eggertsen said.
With support from the National Institutes of Health Ruth L. Kirschstein Predoctoral Individual National Research Service Award, Eggertsen is using computational biological modeling to take on that complexity. He is working to identify FDA-approved drugs that inhibit the signaling activity that drives cardiac hypertrophy. He is also working on making sure the mechanisms that make those drugs work are not impeded.
“We’re trying to increase the number of tools we have in our toolkit for dealing with heart failure in general,” Eggertsen said. “It’s much faster to take a group of previously approved drugs and look at repurposing them than it is to start from square one and design a new drug.”
As a researcher, Eggertsen found himself drawn to the study of cardiac systems because it offers scientists exploration of both the known and the unknown.
“Some of the first computational biology models have been of the heart,” Eggertsen said. “So, it has a long history. There’s a lot to pull from. But there are still these complex problems that we don’t quite have figured out. I like that balance.”
As a member of the Cardiac Systems Biology Group led by Jeffrey Saucerman, a professor of biomedical engineering at UVA, Eggertsen is part of a group of researchers that develop and use biological models of intracellular communication within heart cells. Eggertsen worked from the group’s modeling frameworks to create a computational model that simulates FDA-approved drugs and their effects on cardiac hypertrophy, the growth of the heart that leads to heart failure.
His virtual drug screens identified 38 unique drug-target pairs predicted to inhibit hypertrophy, including midostaurin, a drug used clinically for acute myeloid leukemia. Eggertsen validated the effects of midostaurin in experiments with heart cells, and he is now testing additional drugs in cells and animal models.
“Taylor is taking a creative approach to finding new uses for old drugs, which may accelerate the discovery of drugs for heart disease,” Saucerman said. “I am excited to see whether the drugs Taylor has identified can pass the next hurdles in the long path toward clinical translation.”
Eggertsen joined the field of biomedical engineering to combine concepts from biology, math and engineering and apply them to solutions in medical science. This work, along with its recognition by the National Institutes of Health, makes him feel like he’s on the right track.
“The NIH award helped to confirm for me that my research is important, and that this approach could be useful for a lot of different applications,” Eggertsen said.
Eggertsen envisions applying his virtual drug screening approach to evaluate and develop other drugs and treat other diseases. He hopes to conduct pharmaceutical research in industry, where technologies like predictive modeling are gaining ground.
“There are a lot of incredible advancements that are happening right now,” he said. “It’s an exciting time to get into this field, which is changing a lot. I’m really interested in being a part of that.”