Neonatal Salivary Genomic Profiles To Access Feeding Tolerance and Disease

描述(由申请者提供)：这是对Jill L.Maron博士的临床科学家发展指导奖的申请。在戴安娜·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、假设驱动的转换研究项目，使用非侵入性新生儿唾液基因组图谱来生成有关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博士之前在微阵列分析方面的成功，以及关于早产儿唾液表达谱的有前景的初步数据，为这项研究提供了基础。这项翻译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的发育准备情况，婴儿对喂养的耐受性，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周出生的婴儿的唾液样本中提取的RNA进行完整的转录组基因表达分析。在开始喂养之前和开始口服喂养期间收集唾液，以记录适当的消化运动和成功的口服喂养所需的发育成绩单的时间进程和外观。在引入肠道饲料期间将采集额外的样本，检查消化酶、炎症和免疫调节生物标记物的基因表达，以评估婴儿对饲料的耐受性。 最后，在一小部分婴儿中，将在NEC急性期和恢复期采集唾液样本，以更好地了解其病理生理学。在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博士和Gil Alterovitz博士的帮助下，随着时间的推移，将对同一婴儿的一系列唾液样本进行先进的生物信息学比较和分析，以产生重要的基因和蛋白质相互作用，从而阐明早产儿的生物和病理过程。马龙博士将定期与她的合作者见面，并参加生物信息学、科学写作和翻译研究方面的研究生研讨会。这笔赠款为她提供了必要的培训和教育，以实现她成为一名R01资助的独立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.