Research

With more NIH funding than almost any other medical school-based department of pediatrics in the Northeast, Columbia’s physician-scientists work to address the greatest health threats facing children in the 21st century: obesity, cancer, infectious diseases, diabetes, genetic diseases, heart disease, asthma, and the impacts of prematurity. Our faculty employ cutting-edge research tools such as molecular diagnostics and personalized medicine, and foster wide-ranging and fertile collaborations throughout the university, as well as nationally and internationally. Our goal is to rapidly apply our discoveries to patient care, and to directly benefit the diverse patient community in our region and children around the nation and globe. Discovery and innovation reside in the DNA of our department.

Over the past year investigators in the Department of Pediatrics continued our long-standing commitment to innovation through new and ongoing research initiatives. Some 2022 highlights below:

A New Treatment Paradigm for Pediatric Brain Tumors

The brain is shielded from most toxins and pathogens by a highly complex network of blood vessels—the blood-brain barrier—that restricts the size and chemical composition of molecules that can cross through it and into brain tissue. This barrier is also one of the major challenges neuro-oncologists face in treating brain tumors: most therapeutic agents are not able to penetrate the blood-brain barrier to reach brain and spinal cord tumors, or do so only in very low and ineffective amounts. For decades researchers have tested new agents in both pediatric and adult brain tumors with little success, “and there is tremendous room for improvement,” says Columbia pediatric oncologist Luca Szalontay, MD. Dr. Szalontay and radiation oncologist Cheng-Chia Wu, MD, PhD, co-leaders of Columbia’s Initiative for Drug Delivery Innovation (IDDI), have opened a trial of a noninvasive, focused ultrasound approach that separates the cells lining the vessel walls to open the blood-brain barrier, enabling higher concentrations of an effective drug—in this study the chemotherapeutic agent etoposide—to enter the brain. The IDDI team hopes to impact the currently dismal outlook for the 700 children in the U.S. diagnosed each year with a specific type of brain tumor called diffuse midline glioma. “We hope to show that, using smaller doses of an active drug, we can achieve the same, or even better results, and avoid the systemic side effects for these children,” Dr. Szalontay says. 

Stent vs Shunt in Infants with CHD: Which is Best?

Babies with some types of congenital heart disease—pulmonary atresia, pulmonary stenosis, Tetralogy of Fallot, hypoplastic right heart anomalies, for example—often lack a working connection between the heart’s right ventricle and the pulmonary artery. Because this connection is missing, the heart is unable to direct blood to the lungs, where blood cells would normally pick up oxygen for distribution to the rest of the body. Children with this condition, called ductal-dependent blood flow, cannot survive without interventions to increase the flow of blood to their lungs. Cardiologists and cardiac surgeons currently use two different safe and effective procedures to treat this problem, one involving surgical placement of a shunt, and the second, an interventional procedure to implant a stent. Babies who undergo the stent procedure go home sooner, and since they spend less time in the hospital they’re less like to have developmental delays, but they also need more repeat interventions than infants who receive shunts. Cardiologists and surgeons at different centers tend to prefer one approach over the other, based on their own training and experiences. Through a new multicenter trial launched in 2022 called COMPASS, co-chaired by Chris Petit, MD, director of the Division of Pediatric Cardiology at Columbia, researchers are comparing the outcomes of newborns who receive a stent to those who receive a shunt at 23 North American medical centers. Researchers will follow children in each group to see how well pulmonary arteries grow and function over time, as well as other outcomes measures.

Shedding Light on Natural Killer Cells: The NEAR program

Natural killer (NK) cells are key elements of the innate immune system. They inhibit the growth of many kinds of malignancies and the spread of microbial infections. In children and adults with natural killer (NK) cell deficiency syndromes, NK cells are absent, deficient, or dysfunctional. Columbia’s NEAR Program, led by department chair Jordan Orange, MD, PhD, brings together collaborating specialists in pediatric immunology, allergy, and rheumatology to assess infants, children, and adults whose symptoms suggest they may have an NK cell or primary immunodeficiency disease. In the collaborative independent research laboratories of Dr. Orange and of Emily Mace, PhD, lab members use genetic, biochemical, and cell biological techniques, including quantitative imaging and image analyses, to understand human natural killer (NK) cell development and function. The team offers diagnosis, evaluation, testing, and access to research studies. With the NEAR team’s two 2022 publications, in the Journal of Clinical Investigation Insights (here and here), program members are expanding our understanding of the role of specific genetic mutations in NK cell deficiencies.

Uncovering the Placenta’s Role in Brain Development

During pregnancy the placenta, the interface between mother and fetus, performs a multitude of critical functions: it ferries oxygen and nutrients from the mother to her fetus, filters toxins from the fetal blood supply, allows the maternal and fetal immune systems to coexist, regulates exposure to stress hormones such as cortisol, and much more. “It performs all the many functions the fetus needs before its organs are completely formed,” says Anna Penn, MD, PhD, Columbia’s chief of neonatology. For the past 15 years Dr. Penn has been studying what happens when hormones key to healthy brain development are altered during gestation by prematurity or placental insufficiency—and why disorders such as cerebral palsy, autism, and schizophrenia can result. She initially focused on her research on why male preterm infants are at higher risk for poor neurologic outcomes than females. In research published in 2021 she showed that exposure to low levels of the placental hormone allopregnanolone altered the development of the cerebellum in males; this brain region is important for motor function and emotional control. A single dose of the hormone during late pregnancy shifted their behavior back into the normal range, she showed, “the first strong example of a hormone that alters neurodevelopment in such a striking way.” In a 2022 study her team showed that development of a different brain region, the sensory cortex, was altered in females exposed to low levels of the same hormone. Her future work will continue this focus on sex-linked differences in brain development, and therapeutic strategies that could prevent devastating neurodevelopmental disorders linked to loss of placental function.

Columbia Joins Comprehensive Nationwide Study of Long COVID

Pediatric researchers at Columbia have joined with colleagues at 25 institutions across the country to understand more about long COVID and to mitigate its future impact. The Columbia team is receiving up to $9.4 million in funding to learn about long COVID in children and young adults as part of NIH’s REsearching COVID to Enhance Recovery (RECOVER) initiative. “There is a misperception that children and adolescents cannot get long COVID, and we know that is not true. The goals of RECOVER are to better understand how many children are affected by long COVID, what the long-term effects are, and what factors put children and adolescents at greatest risk. Our ultimate goal is to help prevent and better treat long COVID and to help those affected fully recover,” says hub principal investigator Melissa Stockwell, MD, MPH, chief of the Division of Child and Adolescent Health and chair of the RECOVER Pediatric Study Design Committee. Dr. Stockwell is co-leading the Columbia hub with co-PI Josh Milner, MD, chief of the Division of Allergy, Immunology, and Rheumatology, and co-PI pediatric cardiologist Erika Berman Rosenzweig, MD. As one of 10 pediatric/perinatal teams in the NIH initiative, Columbia has begun recruiting what will be 20,000 children and young adults across all teams, including those with long COVID, those who recovered completely, and those who never had COVID. The study is also recruiting parents and caregivers. The Columbia hub has recruited nearly 500 participants and is one of the lead enrolling hubs. The RECOVER initiative’s national study of tens of thousands of individuals involving more than 100 researchers is a $470 million NIH project. 

Innovation Nucleation Fund Awardees in 2022

The department’s Innovation Nucleation Fund (INF) brings a venture capital approach to great ideas in children’s health research by offering seed funding to innovators with the most promising projects across our mission: advocacy, clinical, education, basic/translational research, and clinical/translational research. Now in its third year, the fund allows our faculty the freedom to pursue innovative and bold ideas that could lead to the next breakthrough for children and their families.

2022 INF Awardees

INF Clinical Program

• Sarah Ann Anderson MD, PhD (CAH): “Achieving Equitable Healthcare Outcomes: Establishing a Multidisciplinary Clinical Pathway Process using Cannabinoid Hyperemesis Syndrome as the Model”

INF Advocacy Program

• Sumeet Banker MD, MPH and Dodi Meyer MD (CAH): “Piloting a LatinX Family Advocate for Hospitalized LEP Children and Families”

INF Education Program

• Kathleen Brennan, MD (Neonatology): “Novel Interdisciplinary Curriculum to Teach Antenatal Counseling at the Edge of Viability”

INF Basic/Translational Research

• Danielle Ahn, MD (CCHM): “The Role of Immunometabolism in Klebsiella pneumoniae Colonization of the Airways of Pediatric Patients"

INF Clinical/Translational Research

• Aimee Layton, PhD and Michael Fremed, MD (Cardiology): “Telehealth Based Cardiopulmonary Rehabilitation To Improve Outcomes In Children and Adolescents with Congenital and Acquired Heart Disease”

INF Education Program – Faculty Award

• Ileana Vargas-Rodriguez, MD (Endocrinology): “NextGen Chefs: Building Culinary Connoisseurs for Healthy Future Societies Through Delicious Wholesome Home Cooking”

INF Clinical Program – Faculty Award

• Vincent Duron, MD (Surgery): “From Womb to Home: The Morgan Stanley Children’s Hospital Pre-Peri-Postnatal (PPP) Treatment and Research Program”