Healing the Lungs

Healing the Lungs

Y.S. Prakash, MD, PhD, found his way to babies and their lungs through serendipitous turns at every stage of his career.

By Jennifer Nelson

Y.S. Prakash, MD, PhD, talks about life’s forks in the road as casually as deciding between chocolate and vanilla ice cream. “I grew up in the Indian system, and back then, as is now, it’s more a British-based system where during high school you decide if you want to go into medical school or engineering, which is the typical split,” explains Prakash, professor of physiology and anesthesiology and chair of the Department of Physiology and Biomedical Engineering at Mayo Clinic in Rochester, Minnesota. 

Fascinated by engineering, but also biology and medicine, Prakash went after both disciplines. He took his entrance exams for the Indian Institutes of Technology and applied to top medical schools. But after he was accepted into both engineering and medical school, he was forced to choose. Though torn, he ultimately chose to go into engineering first—developing an engineering platform with its foundations in critical thinking and analysis—before heading into medicine.

After receiving a scholarship to go to the University of Southern California (USC), Prakash arrived in the U.S. in 1990 to earn a PhD in biomedical engineering. That’s where he met former APS President Gary Sieck, PhD, FAPS, a well-known scientist working on neuromotor control. Fascinated by the work, Prakash joined Sieck’s lab, but within three months he was presented with another fork in the road. Sieck was heading to the Mayo Clinic. “I could stay at USC and take on a new adviser or move with him.”

Prakash’s department chair at the time—a respiratory physiologist who had recruited him to USC—told him that when you think of any field in medicine that’s important, you’ll find somebody at Mayo Clinic doing it. That was the motivation he needed. Prakash packed his worldly belongings in the back of his Brazilian-made Volkswagen Fox and drove from Los Angeles to Rochester to join the Mayo graduate school. That was 31 years ago this past summer.

Following His Passion

When Prakash arrived at Mayo Clinic, there was no biomedical engineering track. Instead, he entered the physiology track, which was run by a biomedical engineer. Biomedical engineering training, the physiology field and working with Sieck was a good fit, and Prakash earned his PhD in respiratory physiology. During that time, he met Mathur Kannan, PhD, a University of Minnesota faculty member who was doing a sabbatical in Sieck’s lab working in airway diseases and asthma.

Working alongside Kannan, Prakash found his passion in the study of the lungs. But, he was equally fascinated by cardiac muscle physiology. Surrounded by the Mayo Clinic environment only heightened his interest in medicine, and working with anesthesiology colleagues inspired him to get his medical degree as well. He began to investigate why anesthetics affect the neonatal heart more than they do the adult heart. Working as a postdoc, Prakash wrote his first R01 grant and applied to medical school.

After he was accepted into medical school, his program officer said he could keep his grant and go to med school. Prakash spent four years at the University of Minnesota Medical School while running his R01 at Mayo. Upon completing medical school, he put his grant on the shelf while he was an anesthesiology resident at Mayo. Meanwhile, he was gravitating toward becoming a lung biologist and wanted to study asthma and airway diseases, so he wrote an entirely new grant once he finished residency. He also married another physician-scientist, Christina M. Pabelick, MD, a pediatric anesthesiologist who was writing a grant of her own. 

By 2009, Prakash and his wife—along with an experienced technician, a supportive chair and a small amount of money from the two R01 grants—began a three-person nascent lab doing airway diseases work, studying asthma across the age spectrum.

As they developed their careers exploring adult asthma, they met Richard Martin, MD, of Case Western Reserve University in Cleveland. Martin was a world-renowned neonatologist exploring the impact of premature birth on lung diseases. Prakash and Pabelick had long been passionate about understanding why premature babies who are exposed to oxygen in the neonatal intensive care unit (NICU) or are put on mechanical ventilation get asthma later in life. The new collaboration excited them as they began to pursue this avenue of research, which they have now been doing for the past 12 years. 

Prakash wants to understand common versus distinct mechanisms of lung disease across the age spectrum and transfer those ideas from airway diseases to pulmonary vascular disease or other conditions. Some of his team’s work includes looking at what happens to the neonatal lung when it gets stretched (as would happen with mechanical ventilation or continuous positive airway pressure therapy, or CPAP). They also want to understand why asthma occurs more in women than in men (boys have more asthma than girls, but women have more asthma than men until menopause), what inflammatory and growth factors contribute to asthma, and why asthma occurs in older people. Separately, ongoing work explores mechanisms of pulmonary hypertension. 

A Focus on Babies

When asked why Prakash wanted to focus on infants and the neonatal lung he says it’s because it’s not a baby’s fault. “All you have to do is walk through a neonatal ICU and see little preemies and see that’s where you want to be.” The ability to make a lifelong difference lies in early intervention, he says.

There’s no such thing as a good amount of oxygen to give to a baby, for example. Giving too little oxygen is bad for the growing baby, but giving too much oxygen, even a little bit, can be detrimental to how the airway grows. It becomes fibrotic and stiffens up, not working as well as the baby grows. Prakash’s team has focused on how controlling oxygen makes a big difference. There also may be novel ways to make the airway grow better. Pabelick and Prakash are looking at things such as hydrogen sulfide as an inhaled bronchodilator that might be beneficial in the short or long term. 

Instead of placing babies on mechanical ventilators in the NICU, they are placed on nasal CPAPs. However, while that may be helpful early on, it might be harmful in the long run because it stretches what is a very compliant airway, Prakash says. Understanding the impact of stretch on the developing airway is important so medical teams can do only what is minimally necessary to keep the baby healthy as they come out of the NICU.

“It’s very, very satisfying to explore some of these concepts,” Prakash says. “Obviously, it would be great to do clinical trials, but the threshold for working with babies is a little different than adults.”

Therefore, more needs to be done in research labs. “We’ve gotten to take care of people in our clinical roles, and that’s been incredibly satisfying, but it has been equally satisfying to be able to participate in this exciting research, and, importantly, to mentor the next generation of scientists and clinician-scientists,” Prakash says. “Today, we have 17 people in the lab, including Christina and me. We are only as good as the people we work with, and we have been simply fortunate to have outstanding people come through.”

When Prakash and Pabelick are not conducting research, they love to travel the world, which provides fodder for Prakash’s photography hobby. The couple lives in the Minnesota countryside, where they enjoy working in their flower and vegetable gardens. 

Prakash’s work shows him the preciousness of life. “You learn to appreciate everything you have and make the best of it,” he says. “So, we work hard because there’s a genuine appreciation for how fragile life is, and making a difference keeps our passion alive.”

This article was originally published in the September 2021 issue of The Physiologist Magazine.