Elena Goncharova, Phd

Biomedical Research Grant; Acute Lung Injury Scholar

Elena Goncharova became interested in pulmonary arterial vascular smooth muscle cells while receiving her PhD in cardiology in Russia. When she came to the University of Pennsylvania for her postdoctoral studies, she began to study smooth muscle cells in a rare lung disease called pulmonary lymphangioleiomyomatosis (LAM), and found her calling. In LAM, smooth muscle cells grow abnormally; invading the airways, as well as blood and lymph vessels. “I worked with smooth muscle cells for years and have a long-term interest in smooth muscle cell behavior in diseased conditions,” she says, “so I thought maybe I could contribute knowledge that will help patients.”

A life-threatening complication of LAM is pulmonary arterial hypertension (PAH), which also affects people with other lungs diseases including chronic obstructive pulmonary disease (COPD) and cystic fibrosis. In PAH, the pulmonary arteries constrict abnormally, which allows less blood to circulate through the lungs to pick up oxygen. For unknown reasons, exposure to chronic lack of oxygen, called hypoxia, triggers the growth of smooth muscle in the walls of the pulmonary arteries that leads to a thickening of artery walls, high blood pressure and heart failure. “These smooth muscle cells are masters of growth and survival,” Dr. Goncharova says. “They grow abnormally and a person ends up with layers and layers of smooth muscle cells, clogging the arteries. A person with PAH can’t exercise, their quality of life decreases, and their life expectancy is shortened.”

“A person with PAH can’t exercise, their quality of life decreases and their life expectancy is shortened. I hope that my research will contribute knowledge that will help patients with PAH.”
Dr. Goncharova decided to focus her research on a protein called mammalian target of rapamycin (mTOR), which has been shown to regulate cells growth and proliferation. With the assistance of an American Lung Association Research Award, Dr. Goncharova is investigating ’what activates mTOR and how mTOR acts to promote vascular smooth muscle cell growth. “If we can understand the role mTOR plays in smooth muscle cell growth, it will help us learn how to suppress it,” she says. Drugs that inhibit mTOR, including rapamycin, are currently being tested against several forms of cancer. Dr. Goncharova says that if her lab is able to unravel the molecular mechanism by which mTOR promotes smooth muscle growth in the lungs, it could lead to development of new therapies to inhibit smooth muscle cell growth in pulmonary arteries inPAH.