Neonatal Salivary Genomic Profiles To Access Feeding Tolerance and Disease

描述（由申请人提供）：这是Jill L. Maron博士申请指导临床科学家发展奖的申请。在Diana Bianchi博士领导的强大指导团队的指导下，Maron博士开发了一个独立的，假设驱动的转化研究项目，使用非侵入性新生儿唾液基因组图谱来生成关于早产儿新生儿喂养并发症的重要和新颖的基因组和蛋白质组学数据。Maron博士先前在微阵列分析方面的成功和早产儿唾液表达谱的有希望的初步数据为本研究提供了基础。这个转化研究项目有三个具体目标，包括使用早产儿的唾液基因组表达谱来更好地了解婴儿对喂养的发育准备，婴儿对饲料的耐受性以及胃肠道系统的病理状况，坏死性小肠结肠炎（NEC）。为了实现这些目标，将对从妊娠28-32周出生的婴儿连续收集的唾液样本中提取的RNA进行全转录组基因表达分析。在开始喂食之前和开始口服喂养期间将收集唾液，以记录正常消化运动和成功口服喂养所必需的发育转录本的时间过程和外观。在引入肠内饲料期间，将采集更多样本，检查消化酶、炎症和免疫调节生物标志物的基因表达，以评估婴儿对饲料的耐受性。

DESCRIPTION (provided by applicant): 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.