The moment a baby is born, their body undergoes one of the most significant transitions in human life. Oxygen supply shifts from the placenta to the lungs, which must inflate and begin working for the first time.

Shyamala Dakshinamurti, a professor of U of M’s pediatrics and child health department, studied what happens when this transition does not go smoothly. Her work is focused on pulmonary hypertension of the newborn, a condition where blood vessels in the lungs remain constricted, preventing oxygen from reaching the bloodstream.

“Anywhere between one to six per thousand babies is enough short of oxygen during delivery to develop […] pulmonary hypertension of the newborn,” Dakshinamurti said. Even if the baby breathes, the blood does not reach the lungs to pick up oxygen.

Dakshinamurti works in the neonatal intensive care unit, where she regularly treats newborns with oxygen problems. Early in her training, she was frustrated by how often physicians had no clear answers for worried parents. This inspired her to become a researcher.

Her personal connection to the disease deepened years later, when she learned she had a  cousin in India who had died as a newborn from pulmonary hypertension. It made her realize “how frequently it occurs and how unlikely we are to hear it talked about within our families.” For her, “it was a greater impulse to keep doing the research because this is so little appreciated and understood.”

A common drug used to treat pulmonary hypertension is nitric oxide gas, which relaxes blood vessels through a different pathway. But about a quarter of newborns with pulmonary hypertension do not respond to it. Even when it works, nitric oxide can also cause changes that limit its own effectiveness over time.

“The very drug we’re using to treat the disease can increase the likelihood of the enzymes not working,” Dakshinamurti said. “In other words, the treatment itself limits its own efficacy over time.”

Her lab studies pulmonary constriction and how oxygen controls the relaxation of blood vessels in the lungs. One focus is on an enzyme called adenyl cyclase, which plays a role in dilating pulmonary arteries.

The team discovered that under low-oxygen conditions, the enzyme becomes chemically modified in a way that prevents it from working. This finding opened the door to seeking to design drugs that can reactivate the enzyme and restore normal circulation in the lungs.

“We currently have a few […] very promising molecules,” Dakshinamurti explained. The goal is to make the drug specific for the lung enzyme, so it can improve treatment without harmful side effects, she added.

Another area of her research examines how too much oxygen can harm newborn lungs. While oxygen is essential for survival, her lab found that even two hours of exposure to 100 per cent oxygen can increase the “constriction activities in the lung and a loss of the relaxation activities in the lung blood vessels.”

“I thought […] two hours of 100 per cent oxygen […] was going to be a control condition,” said Dakshinamurti. However, “two hours of too much oxygen will hurt you,” she added.

According to Dakshinamurti, researchers often base their work on what communities identify as important. But she noted, “the voices we don’t hear are the voices of the dead and the voices of the people who are so traumatized by that experience [death of a newborn].” Dakshinamurti hoped her research will help mitigate the side effects of nitric oxide and will help reduce mortality from pulmonary hypertension, which remains around 10 per cent even in high-resource settings. Her lab is now studying promising drug molecules that may reactivate enzymes in the lungs, with potential applications beyond pulmonary hypertension in newborns.

Dakshinamurti advised students to embrace uncertainty. “You learn more every day. Every day I learn all the things I didn’t know yesterday. I’ve come to realize, feeling stupid is a really good feeling because you’re about to learn something,” she said.