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.
