Jason Gleghorn put himself through school by working as an emergency medical technician. He’s now a Princeton postdoctoral research associate in chemical and biological engineering, but his days of suturing are far from over.
Through the eyepieces of a microscope, Gleghorn operates on microfluidic chips the size of a U.S. dime. He sutures a glass cannula to the trachea of fetal mouse lungs the size of President Franklin Roosevelt’s ear on a dime. The fluid channels of this tiny model are about 100 microns wide — the width of a coarse human hair.
As a member of Celeste Nelson’s research team, Gleghorn constructs these chips to simulate lung cavities. In a project started by undergraduate Jiyong Kwak (Class of 2009), the group is studying the forces that affect fetal lung development, in the hopes of developing new therapies for congenital lung defects, a leading cause of infant mortality.
Nelson, an associate professor of chemical and biological engineering, is focusing on contractile forces, or how cells pull on each other and their surroundings — the same types of forces that give our bodies shape. She is investigating the link between these physical forces and the biochemical signals that determine response to pressure, volume and flow. She is trying to find the source of these biochemical signals with the goal of designing new medications that can treat lung defects.
“You don’t combat high blood pressure by bleeding the patient,” Nelson said. “You find the source of high blood pressure and treat it with drugs.”
The challenge lies in measuring and manipulating the mechanical forces that shape our lungs. The fetal lungs are 3-D, constantly changing and, because of their small scale, almost impossible to manipulate.
What’s unusual about the lung, Nelson said, is that it is one of the few organs that functions in a completely different way before birth. Fetal lungs fill with amniotic fluid rather than pumping air. This development works fine unless something goes wrong.
Problems arise due to genetic abnormalities and other causes, such as a reduction in amniotic fluid during pregnancy. A common defect in lung development is fetal pulmonary hypoplasia, which can be caused by congenital diaphragmatic hernia, a hole in the diaphragm.
Doctors, unable to restore pressure in a fetus’ lungs, instead give mothers steroids to speed up lung development. These babies are often delivered prematurely, and may face lung problems later in life — a recent study found that fetal lung defects can lead to emphysema, asthma and chronic obstructive pulmonary disease.
Nelson hopes that her research, which is funded by the National Heart Lung and Blood Institute and the Burroughs Wellcome Fund, will lead to better treatment options for fetuses as well as adults. “If we can understand how mechanical processes, such as the flow of amniotic fluid, help shape the development of the lungs, we can develop new therapies,” she said.