This is an application for a Mentored Clinical Scientist Development Award for Dr. Jill L. Maron. Under the guidance of a strong mentoring team led by Dr. Diana Bianchi, Dr. Maron has developed an independent, hypothesis driven translational research project to use non-invasive neonatal salivary genomic profiles to generate important and novel genomic and proteomic data regarding neonatal feeding complications in premature infants. Dr. Maron's prior success in microarray analyses and promising preliminary data of salivary expression profiles in preterm infants provides the basis for this study. There are three specific aims of this translational research project, which include using salivary genomic expression profiles of premature infants to better understand an infant's developmental readiness to feed, an infant's tolerance of feeds, and a pathological condition of the gastrointestinal system, necrotizing enterocolitis (NEC). To achieve these aims, whole transcriptome gene expression analyses will be performed on RNA derived from salivary samples serially collected from infants born at 28-32 weeks'gestation. Saliva will be collected prior to initiation of feeds and during the introduction of oral feeding to chronicle the time course and appearance of developmental transcripts necessary for proper digestive motility and successful oral feeding. Additional samples will be taken during the introduction of enteral feeds where gene expression of digestive enzymes, inflammatory and immune regulatory biomarkers will be examined to assess an infant's tolerance of feeds. Finally, in a small subset of infants, salivary samples will be obtained during the acute and convalescent stages of NEC to better understand its pathophysiology. With the assistance of collaborators Dr. Donna Slonim, an Associate Professor of Computer Science at Tufts University, and Drs. Marco Ramoni and Gil Alterovitz, bioinformatics specialists at Harvard Medical School, advanced bioinformatic comparisons and analyses will be performed on serial salivary samples from the same infant over time to generate important gene and protein interactions that will elucidate biological and pathological processes occurring in premature neonates. Dr. Maron will meet regularly with her collaborators, and participate in graduate seminars in bioinformatics, scientific writing, and translational research. This grant provides the necessary training and education for her to achieve her ultimate goal of becoming an independent R01 funded researcher.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Clinical Investigator Award (CIA) (K08)
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Pediatrics Subcommittee (CHHD)
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Grave, Gilman D
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Tufts University
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Maron, Jill L; Hwang, Jooyeon S; Pathak, Subash et al. (2015) Computational gene expression modeling identifies salivary biomarker analysis that predict oral feeding readiness in the newborn. J Pediatr 166:282-8.e5
Maron, J L; Johnson, K L (2015) Comparative performance analyses of commercially available products for salivary collection and nucleic acid processing in the newborn. Biotech Histochem 90:581-6
Romano-Keeler, J; Wynn, J L; Maron, J L (2014) Great expectorations: the potential of salivary 'omic' approaches in neonatal intensive care. J Perinatol 34:169-73
Maron, Jill L; Johnson, Kirby L; Dietz, Jessica A et al. (2012) Neuropeptide Y2 receptor (NPY2R) expression in saliva predicts feeding immaturity in the premature neonate. PLoS One 7:e37870
Maron, Jill L; Dietz, Jessica A; Parkin, Christopher et al. (2012) Performing discovery-driven neonatal research by transcriptomic analysis of routinely discarded biofluids. J Matern Fetal Neonatal Med 25:2507-11
Dietz, Jessica A; Johnson, Kirby L; Wick, Heather C et al. (2012) Optimal techniques for mRNA extraction from neonatal salivary supernatant. Neonatology 101:55-60
Maron, Jill L (2011) Exploring the neonatal salivary transcriptome: technical optimization and clinical applications. Clin Biochem 44:467-8
Maron, Jill L (2011) Exploring the neonatal salivary transcriptome: technical optimization and clinical applications. Clin Biochem 44:467-8
Bianchi, Diana W; Maron, Jill L; Johnson, Kirby L (2010) Insights into fetal and neonatal development through analysis of cell-free RNA in body fluids. Early Hum Dev 86:747-52
Maron, Jill L; Johnson, Kirby L; Rocke, David M et al. (2010) Neonatal salivary analysis reveals global developmental gene expression changes in the premature infant. Clin Chem 56:409-16