When a baby is born, its first breath marks an amazing transition: the unconscious adaptation from receiving oxygen from its mother’s placenta to breathing on its own. In about 6 out of every 1,000 live births, however, newborns struggle to breathe without intervention.
Children’s respiratory biologist Paul T. Schumacker, PhD, is making important discoveries about the mechanisms that block this natural transition — discoveries that may one day lead to better treatments for babies struggling to take their first breath.
At birth, cells in the lungs and heart detect changes in oxygen tension, triggering a series of reactions that tell the baby to breathe air into its lungs.
Sometimes, however, these oxygen-sensing cells send the wrong signals, usually as a result of complications during pregnancy or due to prematurity. Instead of relaxing, the smooth muscle cells of the heart contract, causing a decrease in blood flow through the lungs and lowered blood oxygen levels. The result is a potentially fatal condition: persistent pulmonary hypertension.
Dr. Schumacker is studying how these cells, at the molecular level, are able to sense changes in the source and amount of oxygen they receive. He says a better understanding may lead to the development of therapies that will block the signaling pathway that causes the blood vessels in the lungs to constrict. “The ability to block this response with a narrowly targeted drug could be very effective in treating these newborns,” says Dr. Schumacker.
In particular, Dr. Schumacker is focusing on the oxygen-sensing abilities of mitochondria, small, energy-producing bodies inside cells. When they sense changes in oxygen levels, mitochondria send signals that trigger adaptive responses in the cell. In collaboration with another research group, Dr. Schumacker’s lab has discovered a small molecule that binds to mitochondria and blocks their ability to send signals that trigger the constriction of these blood vessels. The discovery was made in a set of experiments searching for naturally occurring small molecules made by bacteria or fungi that have effects on human cells. He says this discovery may have implications for cancer as well, as it may be possible to block the signals generated by cancer cells that cause blood vessels to grow into a tumor.
Says Dr. Schumacker, “I was recently flying over Chicago, and as I looked down at our magnificent city I thought, ‘How do you build such a city?’ And the answer is ‘one brick at a time.’ It’s incremental and evolutionary. And science is the same way. How do you make fantastic discoveries? You make them one step at a time.”
This article first appeared in the fall 2010 issue of Heroes magazine.