New Fralin Biomedical Research Institute at VTC scientist pursues heart disease treatments

A quarter of Americans will die from heart disease, according to the Centers for Disease Control and Prevention.

Of those deaths, about 45 percent are attributed to coronary artery disease – a chronic condition caused by thickened blood vessels. Surgeons can remove plaque buildup and open up narrowed vessels with a stent, but sometimes this procedure cues an adverse inflammatory response.

“Just like cutting your skin, the endothelial cells that make up the innermost part of blood vessels can become damaged by the stent,” said Scott Johnstone, an assistant professor at the Fralin Biomedical Research Institute at VTC. “Sometimes when that happens, the artery’s smooth muscle cells start dividing rapidly while the endothelium heals, which ends up narrowing the blood vessel again.”

Healthy smooth muscle cells in blood vessels aren’t supposed to divide. But when they’re injured or inflamed, this cycle gets disturbed.

Johnstone, who joined the Fralin Biomedical Research Institute’s Center for Heart and Reparative Medicine Research this summer, studies the proteins involved in heart disease progression and the body’s inflammatory response. The lab researches how certain molecules are involved in rapid cell division, or cell proliferation – a process underlying multiple diseases, including heart disease and cancers.

Johnstone’s team is designing drugs that interrupt protein interactions to curb pathological cell division. So far one of these therapeutic peptides has received a provisional patent. But developing these peptides isn’t an easy feat. The drug needs to instruct one cell type in the blood vessel to stop dividing, without interrupting normal cycles in neighboring cells.

“In cardiovascular disease, we’re looking for that gold standard: where endothelial cells divide to promote vessel repair, and pathological division of smooth muscle cells is stopped,” said Johnstone, who is also an assistant professor in the department of biological sciences in Virginia Tech’s College of Science.

Johnstone, who began his career as a cell and molecular biologist before transitioning to cardiovascular science, has been studying how cells communicate and proliferate for more than a decade.

His laboratory recently described the nuances of how porous signaling channels called pannexins – which help control a cell’s calcium levels, among numerous other functions – regulate inflammation in blood vessels. The study, published this summer in the Journal of Immunology, showed that when pannexin channels are pharmacologically blocked or their expression is genetically inhibited, this suppresses the production and release of a type of proinflammatory molecule called a cytokine. Presence of a specific cytokine, interleukin 1 beta, is a known risk factor in cardiovascular disease.

Understanding the link between these channel-forming proteins and cytokine release could be essential to developing new anti-inflammatory drugs – some of which could even help patients with severe cases of COVID-19.

This summer, Johnstone was among a group of scientists who published an article in the American Journal of Physiology – Lung Cellular and Molecular Physiology that urged researchers to investigate if FDA-approved drugs that target pannexin channels can relieve the hyperinflammation and “cytokine storm” associated with severe COVID-19 cases.

Johnstone’s laboratory uses a variety of experimental techniques – from single proteins expressed in bacteria, to studying how proteins and cells interact in coronary artery bypass samples from human patients. By launching his independent research program at the Fralin Biomedical Research Institute at VTC, Johnstone plans to collaborate with other teams of investigators in the research institute’s Center for Heart and Reparative Medicine Research, including those led by Jamie Smyth and Robert Gourdie, who serves as the center’s director.

“The people are what attracted me to the Fralin Biomedical Research Institute. There are so many great scientists here working on therapeutic design across many disease states, and my research ties in nicely with the institute’s focuses in cardiovascular and cancer research,” Johnstone said. 

Prior to locating his laboratory to Virginia Tech, Johnstone was an instructor of research at the University of Virginia. He also worked as a biomedical sciences lecturer at Glasgow Caledonian University. Johnstone completed an American Heart Association Postdoctoral Research Fellowship at the University of Virginia, where he earned the Outstanding Post-Doc Award and a Lord Kelvin Adam Smith Postdoctoral Fellowship at the British Heart Foundation Glasgow Cardiovascular Research Centre at the University of Glasgow. Born and raised in Scotland, Johnstone earned his bachelor’s and doctoral degrees at Glasgow Caledonian University.