In addition to our regular CRI Activities Update, this month’s Research Focus highlights collaborative work from the team of Mike O’Shea, MD, MPH, Chief of the Division of Neonatal and Perinatal Medicine and Rebecca Fry, Ph.D. Professor, Environmental Sciences and Engineering.

Activities Update: This past month, Kevin Kelly, MD, Toni Darville, MD, Leslie Nelson, and Suzanne Kennedy, PhD, visited the UNC Development Office of Corporate and Foundation Relations to learn more about how they might assist us in funding collaborative research that benefits children. The Corporate and Foundation Relations team fosters collaborations between UNC and industry and foundations, as well as assists with application submissions to these entities. For this relationship to benefit the CRI optimally, the Corporate and Foundation Relations team wants to learn about our current relationships with foundations and industry, in order to enhance these interactions. We will be reaching out to investigators to start this conversation.

This summer we secured the Bioinformatics Auditorium (room 1131) as the location for our CRI monthly luncheon seminar series. Wesley Burks, MD, will kick off the series on Thursday, October 5, at 12:15 p.m. Thereafter, the seminars will regularly occur the second Tuesday of every month. The second seminar will be delivered by David Peden, MD, MS, on Tuesday, November 14. Invitations have been and will continue to be sent through Outlook; please check that the invite is on your calendar. This novel format seminar series will start with lunch and a presentation focusing on the investigator’s latest research efforts. This is followed with time for questions and a 20-minute “Research Development” discussion on building collaborations and securing funding.

Mary Ellen Jones Renovation Update: The builders have relayed that we are still on schedule to have occupancy in the spring of 2019. Construction has begun for the elevated plaza located in the service area between Mary Ellen Jones and Thurston-Bowles.  Plaza construction is expected to last through October.

Research Focus of the MonthTo inform each other of the research interactions in pediatrics, and in the spirit of CRI’s mission to promote collaboration, each CRI update will continue to highlight different investigators’ collaborative efforts. Below is a summary on the collaborative research from Mike O’Shea, MD, MPH, Chief of the Division of Neonatal and Perinatal Medicine and Rebecca Fry, Ph.D. Professor, Environmental Sciences and Engineering.

Mike O'Shea, MD, MPH
Mike O’Shea, MD, MPH

Extremely preterm birth is associated with greatly increased risks of neurodevelopmental impairments and potential childhood behavioral problems. Dr. O’Shea is leading the charge at UNC Children’s to delve into factors that affect early childhood development, performing ongoing research into a cohort of children recruited from 2002 to 2004 into the ELGAN (Extremely Low Gestational Age Newborns) study. ELGAN is funded by the National Institute of Neurological Disorders and Stroke (NINDS) and National Institute of Child Health and Human Development (NICHD). More than 1,500 premature children from across 14 U.S. hospitals, including NC Children’s Hospital, are enrolled in ELGAN. Dr. O’Shea and his ELGAN collaborators in Boston and Germany have found that recurrent or persistent elevations of inflammation-related proteins (ICAM-3, MPO, IL-6, TNF-RI, IL-8, VEGF-R1, VEGF-R2) detected in two-week postnatal blood were associated with attention problems in children at two years of age.

Last year, the NIH launched the $150 million Environmental influences on Child Health Outcomes (ECHO) initiative to research how environmental exposures affect children’s neurodevelopment, chances of developing obesity and asthma, and overall health. By collaborating with other ECHO cohorts, the ELGAN investigators will extend their studies of relationships among initiators of inflammation, placenta epigenetics, neonatal systemic inflammation, and neurodevelopmental outcomes in the offspring. Their published work points to maternal obesity, fetal growth restriction, and placental microorganisms as important antecedents of neurodevelopmental impairments that operate through epigenetic and/or inflammatory mechanisms.

The ELGAN-ECHO study is a prime example of collaboration between basic and clinical science research at UNC. Dr. O’Shea co-led the UNC School of Medicine’s participation in this NIH ECHO initiative with the third phase of the ELGAN study, alongside co-principal investigator Professor Rebecca Fry, PhD, an environmental scientist with the UNC Gillings School of Public Health. This ELGAN-ECHO study will continue to follow the ELGAN cohort to investigate how the placenta senses and transmits information about environmental exposures to the fetus. The study also examines how these exposures lead to early inflammation and affect health later. The children participating in the ELGAN-ECHO study had assessments at 10 years of age (N=889, 81%) and will continue to be evaluated until the age of 18 across psychiatric, cognitive, and neurological health.

Dr. O’Shea brings a wealth of experience in perinatal epidemiology and neurodevelopmental outcomes to the study, while Dr. Fry brings a deep background in epigenetics and systems biology. A recent highlight of their combined efforts is a publication on sex-dependent epigenetic patterning in the placenta. They found differences in methylation patterns of DNA for the innate immune protein Toll-Like Receptors (TLR) 7 and 8. Compared to females, in males TLR7 is hypermethylated while TLR8 is hypomethylated. This may contribute to differential susceptibility to environmental exposures in utero.

Other key collaborators are Karl Kuban (principal investigator for the second phase of the ELGAN Study, Boston Medical Center); Robert Joseph (developmental and cognitive psychologist, Boston University); Jean Frazier (child psychiatrist, University of Massachusetts); Hernan Jara (MRI physicist, Boston Medical Center); Laurie Douglass (child neurologist, Boston Medical Center); Steve Hooper (developmental psychologist, UNC), Julie Daniels (epidemiologist, UNC), Eliana Perrin (pediatrician and child obesity expert, Duke University), Tim Heeren (biostatistician, Boston University), and Matt Psioda (biostatistician, UNC School of Public Health).

For more information on Mike O’Shea’s research, read more about the ELGAN study and the NIH’s ECHO program.

Recent Publications:

1: Yanni D, Korzeniewski S, Allred EN, Fichorova RN, O’Shea TM, Kuban K, Dammann O, Leviton A. Both antenatal and postnatal inflammation contribute information about the risk of brain damage in extremely preterm newborns. Pediatr Res. 2017 May 26. doi: 10.1038/pr.2017.128. [Epub ahead of print] PubMed PMID: 28549057.

2: Tilley SK, Joseph RM, Kuban KCK, Dammann OU, O’Shea TM, Fry RC. Genomic biomarkers of prenatal intrauterine inflammation in umbilical cord tissue predict later life neurological outcomes. PLoS One. 2017 May 11;12(5):e0176953. doi: 10.1371/journal.pone.0176953. eCollection 2017. PubMed PMID: 28493900; PubMed Central PMCID: PMC5426658.

3: Jensen ET, van der Burg JW, O’Shea TM, Joseph RM, Allred EN, Heeren T, Leviton A, Kuban KCK; Extremely Low Gestational Age Newborns Study Investigators. The Relationship of Maternal Prepregnancy Body Mass Index and Pregnancy Weight Gain to Neurocognitive Function at Age 10 Years among Children Born Extremely Preterm. J Pediatr. 2017 Aug;187:50-57.e3. doi: 10.1016/j.jpeds.2017.02.064. Epub 2017 Mar 21. PubMed PMID: 28341527; PubMed Central PMCID: PMC5533624.

4: Joseph RM, Korzeniewski SJ, Allred EN, O’Shea TM, Heeren T, Frazier JA, Ware J, Hirtz D, Leviton A, Kuban K; ELGAN Study Investigators. Extremely low gestational age and very low birthweight for gestational age are risk factors for autism spectrum disorder in a large cohort study of 10-year-old children born at 23-27 weeks’ gestation. Am J Obstet Gynecol. 2017 Mar;216(3):304.e1-304.e16. doi: 10.1016/j.ajog.2016.11.1009. Epub 2016 Nov 12. PubMed PMID: 27847193; PubMed Central PMCID: PMC5334372.

5: Kuban Joseph RM, O’Shea TM, Heeren T, Fichorova RN, Douglass L, Jara H, Frazier JA, Hirtz D, Rollins JV, Paneth N; Extremely Low Gestational Age Newborn (ELGAN) Study Investigators. Circulating Inflammatory-Associated Proteins in the First Month of Life and Cognitive Impairment at Age 10 Years in Children Born Extremely Preterm. J Pediatr. 2017 Jan;180:116-123.e1. doi:10.1016/j.jpeds.2016.09.054. Epub 2016 Oct 24. PubMed PMID: 27788929; PubMedCentral PMCID: PMC5183478.