Premature birth remains a significant health concern and an increasing proportion of very low birth weight infants are surviving. As a consequence, neonatologists are facing an expanding population of infants with poorly-understood diseases in whom prematurity is a major causative factor. Preterm delivery may expose genetic and epigenetic susceptibility to the extraordinary demands of adaptation to the environment of the nursery. New insights, based on modern genetic analysis are required to address this important problem area. Few physician-scientists or biomedical investigators are trained to understand the complex interplay between genes and environment in the immature host. The overall objective of the proposed Genes and Environment in Neonatal Education (GENE) Training Program is to provide research training for clinical and basic science investigators in the design, implementation and analysis of genome-wide genetic and epigenetic studies in neonates. The program is designed to integrate basic genetic training with research skills fundamental to the unique demands of genome-wide investigation. Using a two-mentor model in which a genetics or epigenetics mentor assists the trainee in understanding the application of modern state-of-the- art tools, while a mentor focused on biological problems in the neonate guides the trainee through clinical or developmental analyses specifically geared to understanding diseases in the NICU. A team of experts in genetics, epigenetics, and clinical/translational research has been assembled to facilitate this training effort. These mentors, combined with the outstanding clinical facilities and research cores of the Children's Hospital of Philadelphia, the University of Pennsylvania, the and the Stokes Research Institute will enhance the training experience of MD and PhD post-doctoral fellows and prepare them to become experts in this emerging field of research.

Public Health Relevance

An increasing number of very premature infants are surviving with complex medical problems, reflecting the influence of environmental factors such as prematurity itself or transition to breathing and feeding on a genetically-susceptible neonate. Few scientists are trained to understand the interactions between genes and the unique environment of the premature infant. This training program attempts to correct that deficiency.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Institutional National Research Service Award (T32)
Project #
5T32HD060556-02
Application #
8109409
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Raju, Tonse N
Project Start
2010-07-10
Project End
2015-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
2
Fiscal Year
2011
Total Cost
$203,121
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Rashid, Cetewayo S; Lien, Yu-Chin; Bansal, Amita et al. (2018) Transcriptomic Analysis Reveals Novel Mechanisms Mediating Islet Dysfunction in the Intrauterine Growth-Restricted Rat. Endocrinology 159:1035-1049
Reynolds, L J; Pollack, R I; Charnigo, R J et al. (2017) Increased birth weight is associated with altered gene expression in neonatal foreskin. J Dev Orig Health Dis 8:575-583
Sengupta, Shaon; Yang, Guang; O'Donnell, John C et al. (2016) The circadian gene Rev-erb? improves cellular bioenergetics and provides preconditioning for protection against oxidative stress. Free Radic Biol Med 93:177-89
Flibotte, John J; Jablonski, Angela M; Kalb, Robert G (2014) Oxygen sensing neurons and neuropeptides regulate survival after anoxia in developing C. elegans. PLoS One 9:e101102
Deshmukh, Hitesh; Lioy, Janet (2014) The use of early lung biopsy in detection of fatal pulmonary disease in the neonate. J Pediatr 164:934-6
Jaeckle Santos, Lane J; Li, Changhong; Doulias, Paschalis-Thomas et al. (2014) Neutralizing Th2 inflammation in neonatal islets prevents ?-cell failure in adult IUGR rats. Diabetes 63:1672-84
Deshmukh, Hitesh S; Liu, Yuhong; Menkiti, Ogechukwu R et al. (2014) The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice. Nat Med 20:524-30
Hudock, Kristin M; Liu, Yuhong; Mei, Junjie et al. (2012) Delayed resolution of lung inflammation in Il-1rn-/- mice reflects elevated IL-17A/granulocyte colony-stimulating factor expression. Am J Respir Cell Mol Biol 47:436-44