Andrea Gropman

$5M in federal funding to help patients with urea cycle disorders

Andrea Gropman

Andrea L. Gropman, M.D.: We have collected many years of longitudinal clinical data, but with this new funding now we can answer questions about these diseases that are meaningful on a day-to-day basis for patients with urea cycle disorders.

An international research consortium co-led by Andrea L. Gropman, M.D., at Children’s National Hospital has received $5 million in federal funding as part of an overall effort to better understand rare diseases and accelerate potential treatments to patients.

Urea cycle disorder, one such rare disease, is a hiccup in a series of biochemical reactions that transform nitrogen into a non-toxic compound, urea. The six enzymes and two carrier/transport molecules that accomplish this essential task reside primarily in the liver and, to a lesser degree, in other organs.

The majority of patients have the recessive form of the disorder, meaning it has skipped a generation. These kids inherit one copy of an abnormal gene from each parent, while the parents themselves were not affected, says Dr. Gropman, chief of the Division of Neurodevelopmental Pediatrics and Neurogenetics at Children’s National. Another more common version of the disease is carried on the X chromosome and affects boys more seriously that girls, given that boys have only one X chromosome.

Regardless of the type of urea cycle disorder, when the urea cycle breaks down, nitrogen converts into toxic ammonia that builds up in the body (hyperammonemia), particularly in the brain. As a result, the person may feel lethargic; if the ammonia in the bloodstream reaches the brain in high concentrations, the person can experience seizures, behavior changes and lapse into a coma.

Improvements in clinical care and the advent of effective medicines have transformed this once deadly disease into a more manageable chronic ailment.

“It’s gratifying that patients diagnosed with urea cycle disorder now are surviving, growing up, becoming young adults and starting families themselves. Twenty to 30 years ago, this never would have seemed conceivable,” Dr. Gropman says. “We have collected many years of longitudinal clinical data, but with this new funding now we can answer questions about these diseases that are meaningful on a day-to-day basis for patients with urea cycle disorders.”

In early October 2019, the National Institutes of Health (NIH) awarded the Urea Cycle Disorders Consortium for which Dr. Gropman is co-principal investigator a five-year grant. This is the fourth time that the international Consortium of physicians, scientists, neuropsychologists, nurses, genetic counselors and researchers has received NIH funding to study this group of conditions.

Dr. Gropman says the current urea cycle research program builds on a sturdy foundation built by previous principal investigators Mendel Tuchman, M.D., and Mark Batshaw, M.D., also funded by the NIH. While previous rounds of NIH funding powered research about patients’ long-term survival prospects and cognitive dysfunction, this next phase of research will explore patients’ long-term health.

Among the topics they will study:

Long-term organ damage. Magnetic resonance elastrography (MRE) is a state-of-the-art imaging technique that combines the sharp images from MRI with a visual map that shows body tissue stiffness. The research team will use MRE to look for early changes in the liver – before patients show any symptoms – that could be associated with long-term health impacts. Their aim is spot the earliest signs of potential liver dysfunction in order to intervene before the patient develops liver fibrosis.

Academic achievement. The research team will examine gaps in academic achievement for patients who appear to be underperforming to determine what is triggering the discrepancy between their potential and actual scholastics. If they uncover issues such as learning difficulties or mental health concerns like anxiety, there are opportunities to intervene to boost academic achievement.

“And if we find many of the patients meet the criteria for depression or anxiety disorders, there are potential opportunities to intervene.  It’s tricky: We need to balance their existing medications with any new ones to ensure that we don’t increase their hyperammonemia risk,” Dr. Gropman explains.

Neurologic complications. The researchers will tap continuous, bedside electroencephalogram, which measures the brain’s electrical activity, to detect silent seizures and otherwise undetectable changes in the brain in an effort to stave off epilepsy, a brain disorder that causes seizures.

“This is really the first time we will examine babies’ brains,” she adds. “Our previous imaging studies looked at kids and adults who were 6 years and older. Now, we’re lowering that age range down to infants. By tracking such images over time, the field has described the trajectory of what normal brain development should look like. We can use that as a background and comparison point.”

In the future, newborns may be screened for urea cycle disorder shortly after birth. Because it is not possible to diagnose it in the womb in cases where there is no family history, the team aims to better counsel families contemplating pregnancy about their possible risks.

Research described in this post was underwritten by the NIH through its Rare Diseases Clinical Research Network.

Mihailo Kaplarevic

Extracting actionable research data faster, with fewer hassles

Mihailo Kaplarevic

Mihailo Kaplarevic, Ph.D., the newly minted Chief Research Information Officer at Children’s National Hospital and Bioinformatics Division Chief at Children’s National Research Institute, will provide computational support, advice, informational guidance, expertise in big data and data analyses for researchers and clinicians.

Kaplarevic’s new job is much like the role he played most recently at the National Heart, Lung and Blood Institute (NHLBI), assembling a team of researchers and scientists skilled in computing and statistical analyses to assist as in-house experts for other researchers and scientists.

NHLBI was the first institute within the National Institutes of Health (NIH) family to set up a scientific information office. During his tenure, a half-dozen other NIH institutions followed, setting up the same entity to help bridge the enormous gap between basic and clinical science and everything related to IT.

“There is a difference compared with traditional IT support at Children’s National – which will remain in place and still do the same sort of things they have been doing so far,” he says of The Bear Institute for Health Innovation. “The difference is this office has experience in research because every single one of us was a researcher at a certain point in our career: We are published. We applied for grants. We lived the life of a typical scientist. On top of that, we’re coming from the computational world. That helps us bridge the gaps between research and clinical worlds and IT.”

Ultimately, he aims to foster groundbreaking science by recognizing the potential to enhance research projects by bringing expertise acquired over his career and powerful computing tools to help teams achieve their goals in a less expensive and more efficient way.

“I have lived the life of a typical scientist. I know exactly how painful and frustrating it can be to want to do something quickly and efficiently but be slowed by technological barriers,” he adds.

As just one example, his office will design the high-performance computing cluster for the hospital to help teams extract more useful clinical and research data with fewer headaches.

Right now, the hospital has three independent clinical systems storing patient data; all serve a different purpose. (And there are also a couple of research information systems, also used for different purposes.) Since databases are his expertise, he will be involved in consolidating data resources, finding the best way to infuse the project with the bigger-picture mission – especially for translational science – and creating meaningful, actionable reports.

“It’s not only about running fewer queries,” he explains. “One needs to know how to design the right question. One needs to know how to design that question in a way that the systems could understand. And, once you get the data back, it’s a big set of things that you need to further filter and carefully shape. Only then will you get the essence that has clinical or scientific value. It’s a long process.”

As he was introduced during a Children’s National Research Institute faculty meeting in late-September 2019, Kaplarevic joked that his move away from pure computer science into a health care and clinical research domain was triggered by his parents: “When my mom would introduce me, she would say ‘My son is a doctor, but not the kind of doctor who helps other people.’ ”

Some of that know-how will play out by applying tools and methodology to analyze big data to pluck out the wheat (useful data) from the chaff in an efficient and useful way. On projects that involve leveraging cloud computing for storing massive amounts of data, it could entail analyzing the data wisely to reduce its size when it comes back from the cloud – when the real storage costs come in. “You can save a lot of money by being smart about how you analyze data,” he says.

While he expects his first few months will be spent getting the lay of the land, understanding research project portfolios, key principal investigators and the pediatric hospital’s biggest users in the computational domain, he has ambitious longer-term goals.

“Three years from now, I would like this institution to say that the researchers are feeling confident that their research is not affected by limitations related to computer science in general. I would like this place to become a very attractive environment for up-and-coming researchers as well as for established researchers because we are offering cutting-edge technological efficiencies; we are following the trends; we are a secure place; and we foster science in the best possible way by making computational services accessible, affordable and reliable.”

Lee Beers

Getting to know Lee Beers, M.D., FAAP, future president-elect of AAP

Lee Beers

Lee Savio Beers, M.D., FAAP, Medical Director of Community Health and Advocacy at the Child Health Advocacy Institute (CHAI) at Children’s National Hospital carved out a Monday morning in late-September 2019, as she knew the American Academy of Pediatrics (AAP) would announce the results of its presidential election, first by telephone call, then by an email to all of its members.  Her husband blocked off the morning as well to wait with her for the results.  She soon got the call that she was elected by her peers to become AAP president-elect, beginning Jan. 1, 2020. Dr. Beers will then serve as AAP president in 2021 for a one-year term.

That day swept by in a rush, and then the next day she was back in clinic, caring for her patients, some of them teenagers whom she had taken care of since birth. Seeing children and families she had known for such a long time, some of whom had complex medical needs, was a perfect reminder of what originally motivated Dr. Beers to be considered as a candidate in the election.

“When we all work together – with our colleagues, other professionals, communities and families – we can make a real difference in the lives of children.  So many people have reached out to share their congratulations, and offer their support or help. There is a real sense of collaboration and commitment to child health,” Dr. Beers says.

That sense of excitement ripples through Children’s National.

“Dr. Beers has devoted her career to helping children. She has developed a national advocacy platform for children. I can think of no better selection for the president-elect role of the AAP. She will be of tremendous service to children within AAP national leadership,” says Kurt Newman, M.D., Children’s National Hospital President and CEO.

AAP comprises 67​,000 pediatricians, and its mission is to promote and safeguard the health and well-being of all children – from infancy to adulthood.

The daughter of a nuclear engineer and a schoolteacher, Dr. Beers knew by age 5 that she would become a doctor. Trained as a chemist, she entered the Emory University School of Medicine after graduation. After completing residency at the Naval Medical Center, she became the only pediatrician assigned to the Guantanamo Bay Naval Station.

That assignment to Cuba, occurring so early in her career, turned out to be a defining moment that shapes how she partners with families and other members of the team to provide comprehensive care.

“I was a brand-new physician, straight out of residency, and was the only pediatrician there so I was responsible for the health of all of the kids on the base. I didn’t know it would be this way at the time, but it was formative. It taught me to take a comprehensive public health approach to taking care of kids and their families,” she recalls.

On the isolated base, where she also ran the immunization clinic and the nursery, she quickly learned she had to judiciously use resources and work together as a team.

“It meant that I had to learn how to lead a multi-disciplinary team and think about how our health care systems support or get in the way of good care,” she says.

One common thread that unites her past and present is helping families build resiliency to shrug off adversity and stress.

“The base was a difficult and isolated place for some families and individuals, so I thought a lot about how to support them. One way is finding strong relationships where you are, which was important for patients and families miles away from their support systems. Another way is to find things you could do that were meaningful to you.”

Cuba sits where the Atlantic Ocean, Caribbean Sea and Gulf of Mexico meet. Dr. Beers learned how to scuba dive there – something she never would have done otherwise – finding it restful and restorative to appreciate the underwater beauty.

“I do think these lessons about resilience are universal. There are actually a lot of similarities between the families I take care of now, many of whom are in socioeconomically vulnerable situations, and military families when you think about the level of stress they are exposed to,” she adds.

Back stateside in 2001, Dr. Beers worked as a staff pediatrician at the National Naval Medical Center in Bethesda, Maryland, and Walter Reed Army Medical Center in Washington, D.C. In 2003, Dr. Beers joined Children’s National Hospital as a general pediatrician in the Goldberg Center for Community Pediatric Health. Currently, she oversees the DC Collaborative for Mental Health in Pediatric Primary Care, a public-private coalition that elevates the standards of mental health care for all children, and is Co-Director of the Early Childhood Innovation Network. She received the Academic Pediatric Association’s 2019 Public Policy and Advocacy Award.

As a candidate, Dr. Beers pledged to continue AAP’s advocacy and public policy efforts and to further enhance membership diversity and inclusion. Among her signature issues:

  • Partnering with patients, families, communities, mental health providers and pediatricians to co-design systems to bolster children’s resiliency and to alleviate growing pediatric mental health concerns
  • Tackling physician burnout by supporting pediatricians through office-based education and systems reforms
  • Expanding community-based prevention and treatment

“I am humbled and honored to have the support of my peers in taking on this newest leadership role,” says Dr. Beers. “AAP has been a part of my life since I first became a pediatrician, and my many leadership roles in the DC chapter and national AAP have given me a glimpse of the collective good that pediatricians can accomplish by working together toward common strategic goals.”

AAP isn’t just an integral part of her life, it’s where she met her future husband, Nathaniel Beers, M.D., MPA, FAAP, President of The HSC Health Care System. The couple’s children regularly attended AAP meetings with them when they were young.

Just take a glimpse at Lee Beers’ Twitter news feed. There’s a steady stream of images of her jogging before AAP meetings to amazing sunrises, jogging after AAP meetings to stellar sunsets and always, always, images of the entire family, once collectively costumed as The Incredibles.

“I really do believe that we have to set an example: If we are talking about supporting children and families in our work, we have to set that example in our own lives. That looks different for everyone, but as pediatricians and health professionals, we can model prioritizing our families while still being committed to our work,” she explains.

“Being together in the midst of the craziness is just part of what we do as a family. We travel a lot, and our kids have gone with us to AAP meetings since they were infants. My husband even brought our infant son to a meeting at the mayor’s office when he was on paternity leave. Recognizing that not everyone is in a position to be able to do things like that, it’s important for us to do it – to continue to change the conversation and make it normal to have your family to be part of your whole life, not have a separate work life and a separate family life.”