A magazine for friends of the Warren Alpert Medical School of Brown University.

Room to Breathe

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A lung researcher takes over as pediatrician-in-chief.
Even though she comes from a family of physicians, Phyllis Dennery wasn’t necessarily convinced she’d become a doctor. She considered being an architect, a fashion designer, or a geneticist.

The daughter of Haitian immigrants to Canada, Dennery did find her way into the family business. At the Howard University College of Medicine, she took interest in newborn and premature babies. “I just thought they were so fascinating, so resilient yet so small and fragile. That made me want to practice neonatology,” she says.

Dennery arrived at Brown and Hasbro Children’s Hospital in April to become chair of the Department of Pediatrics and the Sylvia Kay Hassenfeld Professor of Pediatrics. She came from the Children’s Hospital of Philadelphia and the University of Pennsylvania, where she was chief of the Division of Neonatology and Newborn Services. In that role, she learned more about running larger organizations and strategic planning. She started thinking she might like to do that job at the department level.

“I wasn’t particularly thinking I wanted to come to Brown,” Dennery says. But she did know Jack A. Elias, MD, dean of medicine and biological sciences, from various pulmonology societies. “We have similar research interests, and I admired the work he has done and I was fascinated by the idea of coming to a place where I could be part of that as well as run the Department of Pediatrics.”

Rhode Island itself was part of the draw. There’s “the promise of what could be done in a state like Rhode Island, where you have one children’s hospital, one health department, one [major] birth hospital,” she says. “This is a place where you can make a big difference with statewide impact.”

THE BABY LUNG

Dennery also w as determined to continue her research on neonatal lung injury. Though moving and establishing her lab on the Brown campus came with some challenges, “I was fortunate to meet longtime Brown research employees, who are marvelous resources, who help you find your way around,” she says. “The community is small enough and friendly—people want to help each other out.”

Her lab studies the mechanism of lung injury caused by high levels of oxygen. When babies are born prematurely, their lungs are underdeveloped. It’s not that it’s a small lung, Dennery explains. Their lungs are missing key elements that make them function like lungs should.

“When they are born we have to give them supplemental oxygen. We breathe room air, which is 21 percent oxygen; some of these babies need at times 100 percent oxygen,” Dennery says. “Put that together with a vulnerable, small, immature lung, you have a recipe for problems.”

The lungs take signaling cues from the toxicity of the oxygen and begin growing abnormally. They become distended, and they don’t have the right amount of cells to make them expand appropriately. “This is a big problem,” Dennery says, “because it’s a lifelong problem.” Lungs develop during the first six years of life, so if that development is distorted, it can create difficulties that last an entire lifetime.

What happens when one of those babies becomes a smoker at age 20? Or lives in a highly polluted area? Will they develop chronic obstructive pulmonary disease early on? Dennery says because neonatology is a relatively young science, not enough time has elapsed to study the lasting effects of prematurity into adulthood. The first ventilators for babies were introduced in the late 1960s, meaning the oldest survivors are just now in their 50s.

And the damage is not confined to the lung. When babies are on a ventilator, in the hospital environment, they miss the typical cues and experiences that foster healthy brain development. “[They’re] just worried about breathing!” Dennery says. “That’s the big picture and to me that’s why this work is so important. What are the changes that are associated with high levels of oxygen that may make the lung change its pattern of development? Is there a way to change that so you can establish a more normal repair pattern?”

COMMUNITY FOCUS

It’s questions like those that Dennery advises her students to pursue in the lab.

Clyde Wright, MD, assistant professor of pediatrics at the University of Colorado, met Dennery when he applied for the neonatology fellowship at CHOP. He shared her interest in oxygen toxicity.

“I remember interviewing with Phyllis and being so impressed by how her laboratory studies were driven by clinical questions raised in the intensive care unit. It was an easy choice to make, and I elected to join her lab for my fellowship,” Wright says.

“She taught me that questions in the lab should keep you up at night, always thinking, and always referred back to the patients we have been trained to take care of. I can attest to this being her practice, being the beneficiary of many, many emails that arrived well past midnight in response to a question I had or regarding a new thought about what we were doing in lab,” he says.

As a mentor, Wright says Dennery never gave “false encouragement or credit, but when it was due, was incredibly supportive and motivating. Training with her, and being guided by her mentorship, without a doubt has been the singular most important aspect of my career in science.”

That encouraging and supportive nature will serve Dennery well as she works toward her goals for the Department of Pediatrics. While it’s a place where people have always valued education and clinical care, she says, there has not been as much focus on scientific research and publishing discoveries. “I think there are so many good things going on and more to come as we build that we really need to foster a culture of research and academic work here,” she says.

She’s quick to point out that research doesn’t just mean that which is done at the lab bench. Referring back to Rhode Island’s compact size and tight community, Dennery says there is great potential for population studies, understanding trends, and identifying hotspots of disease.

Dennery will be able to carry out that work as part of the leadership of the Hassenfeld Child Health Innovation Institute, established in September through a $12.5 million gift from the Hassenfeld Foundation. The institute will bring together a broad coalition of Alpert Medical School and Brown School of Public Health faculty with community partners, nonprofit organizations, and Rhode Island families in a collaborative effort to address the health needs of children in the state.

With that focus on community, Dennery is excited by Jack Elias’s strategic plan that will bring translational medicine to the Brown academic medical center. She describes her participation in a committee convened by the Institute of Medicine (of which she is now a member) to study the clinical translational science centers across the country. In research, the implementation of a discovery or a new drug or intervention is the hardest part, she says.

“If you find this great new drug, but no one knows about the drug or nobody changes what they’re doing, then you haven’t succeeded,” she says. “You need a plan for implementation and dissemination and sustainability. That’s really the spectrum of research.”

THE PATIENT CONNECTION

Dennery is also gratified to be a member of the Brown Investigators of Respiratory Diseases. BIRDs researchers, roughly 45 in all, study varying aspects of respiratory disease. Their meetings and seminars have already led to collaborations and are making Alpert Medical School a leading research center in the field.

“At most places they talk about neuroscience or the genome, but the lung is something that people don’t care as much about,” Dennery says. “It’s really refreshing to be in a place where that’s an important focus.”

That’s because what happens to your lungs doesn’t just affect your lungs. Researchers have only scratched the surface of conditions such as sleep apnea, which involves breathing but also has detrimental effects on the brain. Dennery recently became interested in how circadian rhythms influence more than just our sleep cycles.

“Researchers started noticing that in people who are chronically jet lagged, their lung function is impacted. If you model that in a mouse, you can show that a mouse that is jet lagged will have deterioration of lung function,” she says. The clock that was thought to be a central system is actually ticking in each tissue, each cell of the body, and it regulates function throughout the day.

Another example is asthma: any emergency medicine physician will tell you that more people come into the hospital with asthma attacks at night.

“We started looking at these clock genes to see if they are altered by high oxygen, by other external cues,” Dennery says. “We’re better about it now, but in the NICU, sometimes people don’t think to cycle lights on and off. Could that make the lung more susceptible to injury and worse function?”

Though an administrator and researcher, Dennery is a neonatologist at heart. Clyde Wright saw the “baby doctor” side of her when he became a father for the first time. “Phyllis came to visit us in the hospital after our daughter was born. I had not seen her in this environment, but she was so incredibly warm, gentle, and loving. It was just so obvious that she truly cared about us and our new little family,” he says.

Dennery’s own family consists of her husband of 28 years, Gregory Mundy, and two children. Ariana, 24, is an early education specialist in Philadelphia and Miles, 21, is a senior at Pomona College in California. There are also “two rescue mutts from Puerto Rico (a long story), aged 12 years … oh, and a granddog named Basil,” she says.

In her research, it’s those fragile, resilient beings that she first set out to help that continue to motivate her.

“My interest in lung injury isn’t just because of the lung,” Dennery says. “It’s because I know there’s a clinical, real problem associated with that.” She sees babies who suffer from lung disease and have significant life changes, who stay in the hospital a long time, and have a cascade of problems.

“Sure, it’s fun and exciting to be in the lab,” she says. “But if I could find something to help babies do better and have fewer issues with lung disease, wouldn’t that be even more exciting?”

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