Neonatal Salivary Genomic Profiles To Access Feeding Tolerance and Disease

描述（由申请人提供）：这是Jill L博士的指导临床科学家发展奖申请。马龙在Diana比安奇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，该项目使用非侵入性新生儿唾液基因组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这项研究提供了基础。这个转化研究项目有三个具体目标，其中包括使用早产儿的唾液基因组表达谱，以更好地了解婴儿的发育准备喂养，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品中衍生的RNA进行全转录组基因表达分析。在开始喂食前和经口喂食期间收集唾液，以记录适当消化运动和成功经口喂食所需的发育转录物的时间进程和外观。在引入肠内喂养期间将采集额外的样本，其中将检查消化酶、炎症和免疫调节生物标志物的基因表达，以评估婴儿对喂养的耐受性。 最后，在一小部分婴儿中，将在NEC的急性期和恢复期获得唾液样本，以更好地了解其病理生理学。在合作者塔夫茨大学计算机科学副教授Donna Slonim博士和哈佛医学院生物信息学专家Marco Ramoni和Gil Alterovitz博士的协助下，先进的生物信息学比较和分析将对同一婴儿随时间推移的系列唾液样本进行，以产生重要的基因和蛋白质相互作用，从而阐明早产儿发生的生物学和病理学过程。新生儿Maron博士将定期与她的合作者会面，并参加生物信息学，科学写作和转化研究的研究生研讨会。该补助金为她提供必要的培训和教育，以实现她成为一名独立的R 01资助的研究人员的最终目标。

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.