On May 15, the Seventh Annual Yale Pediatric Research Forum kicked off with excitement in the Anlyan Center (TAC) as Cliff Bogue, MD and Marietta Vázquez, MD welcomed the keynote speaker, Diana Bianchi, MD. Dr. Bianchi is the director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), a position she has held since August 2016.
In her hour-long keynote, Dr. Bianchi focused on her science — a rare topic for an administrator, especially one at the nation’s largest federal biomedical and public health research institution. For more than 35 years, Dr. Bianchi has maintained a commitment to researching Down Syndrome (DS). She developed a non-invasive prenatal test to diagnose DS using flow cytometry, and as of late last year, 10 million of these tests have been performed. Dr. Bianchi’s research also focuses on fetal treatments for disease, with an emphasis on precision medicine. Dr. Bianchi described her simultaneous preclinical in vivo studies, primarily in mouse models of DS, as well as her parallel in vitro studies of somatic cells, induced pluripotent stem cells and neural stem cells, and brain cells. Both types of studies complement her human studies of fetuses, children, and adults with DS to lead to the validation of candidate drugs to test in human clinical trials. Her proof-of-principle studies in mice and human amniocytes established the potential for apigenin as a prenatal treatment, or fetal therapy, for DS, because apigenin can reduce inflammation and advance the cell cycle. Photo courtesy of NIH.
After Dr. Bianchi’s keynote, the Research Forum continued with the scientific plenary session. It included oral presentations from researchers across Pediatrics. First, Julia Rosenberg, MD, a fellow in the National Clinician Scholars Program, described her analysis of the National Survey of Children’s Health in 2016 as it pertained to mental and behavioral health care among children in immigrant families. Dr. Rosenberg opened by stating that we lack culturally sensitive screens for utilization to health care, since the screens we use are made for U.S. kids. She shared that in her sample of over 50,000 children, those in immigrant families had a lower prevalence of nearly all diagnoses, with the largest difference in ADHD. Children in immigrant families also received less mental and behavioral health treatment. She closed by calling for more research to understand the underlying differences in diagnostics and reasons for differences in treatment access, studies for which the New Haven refugee population may be particularly well-suited. Photo courtesy of YSM.
Following Dr. Rosenberg, a joint presentation by medical student Jacob Lister and undergraduate student Seneca Oxendine demonstrated the role of the N-methyl-D-aspartate (NMDA) glutamate receptor (NMDA-R) in neonatal cortex development. We know that disrupted nervous system development underlies many cognitive and psychiatric disorders, and that the NMDA-R mediates developmental plasticity. The receptor is also disrupted in neurodevelopmental disorders. What is not known, and what this study aimed to address, is the role of the NMDA-R in very early brain development. Lister and Oxendine studied neonatal mice in the first two weeks of life using fMRI. They found that NMDA-R signaling is critical for whole cortex network development, as evidenced by a loss of network specialization during spontaneous activity in NMDA-R knockout mice. These findings indicate that NMDA-R is necessary for neuronal pruning in early development and may offer a biomarker to link animal model and human developmental systems.
Next, residents Kamelia McRae, MD, and Theiju Sebastian, MD presented a unique qualitative study of neonatal abstinence syndrome (NAS). Using an ethnographic approach that focused on interviewing parents of babies experiencing NAS, Drs. McRae and Theiju asked about Yale’s previous approach to managing NAS, the traditional Finnegan Neonatal Abstinence Scoring System (FNASS). FNASS relies on temporary separation of parents and infants while the infant was being treated in the NICU, assessment with a standard subjective withdrawal scoring tool, and frequent medication with morphine. They also asked parents about Yale’s current approach, implemented since 2011, which instead relies on infants rooming in on the Well Newborn unit with the mother, management with the newer Eat, Sleep, Console approach (called ESC), and rare use of medication. (A paper on ESC by Yale Department Pediatrics researchers was published in 2018.) With the old approach, infants spent an average of 21 days in the hospital; with the new approach the average stay is now five days. Relying on a lived experience framework, Drs. McRae and Theiju interviewed parents in-person and over the phone. Overall, they found that parents had a very positive perception of ESC compared to the old approach, with interview responses indicating a preference for parented-centered care, with mothers at the frontline of treatment, and a preference for rooming in and little to no medication. However, the authors also found that parents had unclear expectations about their hospital stay, with a lack of information about NAS from their prenatal provider, and they also experienced large variations in breastfeeding support, understanding, and practice. Drs. McRae and Theiju concluded that better communication with families is warranted, including around evidence-based breastfeeding education, as is the creation of a non-judgmental environment throughout the hospital regarding NAS.
To close the oral sessions, Jinlin Li, PhD, associate research scientist, presented his research into the genetics of Epstein-Barr Virus (EBV). EBV is one of eight known human herpesvirus types and is associated with many diseases including multiple types of cancer worldwide. The EBV life cycle switches from latent to lytic, making it able to produce new copies of the virus. Dr. Li shared his research into late genes for EBV, which encode for structural proteins that regulated viral events like virus attachment and internalization during infection and protect infected cells from immune responses. Because the mechanisms regulating the transcription of late genes are not well defined, research in this field is crucial. Dr. Li shared that a gene called BGLF.3 is essential for the expression of late genes, and that phosphorylation of BGLF.3 at threonine 42 (or T42, an essential amino acid) is essential for late gene expression. This phosphorylation also regulates the assembly of the viral pre-initiation complex, which is essential for EBV late gene transcription. Dr. Li’s research sheds new light on our understanding of the complex mechanisms underlying the transcription of late genes in EBV, which could hold potential for future therapeutic targets.
The Research Forum ended with a two-hour-long poster session and reception in the TAC lobby. The 57 poster topics were as diverse as the scientists presenting them, ranging from preclinical animal studies into developmental genetics, to treatments of children and adolescents for various health issues, to physicians, unions, and strikes.
Next year’s Pediatric Research Forum will have a high bar to meet!