Biochemical Predictors of Necrotizing Enterocolitis

描述(由申请人提供)：候选人凯瑟琳·E·格雷戈里，博士，RN，目标是成为一名独立的临床调查员，将领导她所在领域的以患者为中心的创新研究计划。格雷戈里博士的研究计划将利用尖端的生化分析(即微生物组)和生物信息学预测策略(即代谢组学)产生新的疾病发病机制和预测模型。作为她迄今为止的研究培训和经验的一部分，她已经确定了早产儿坏死性小肠结肠炎(NEC)的临床预测因素。这项工作扩大了对NEC先兆的了解，远远超出了早产儿和人口统计学的范围。格雷戈里博士将继续关注NEC，这是新生儿护理中尚未解决的主要问题之一，也是早产儿最常见的胃肠道急症，也是早产儿营养、生长和神经发育异常的主要原因。需要新的范式来理解NEC的病因学和病理生物学，这将有助于我们对这种疾病和其他疾病的预测。这项研究提出的中心假设是，可以使用非血清生物样本(即尿液和粪便)在极低胎龄新生儿中预测NEC。使用尿液进行生物标记物分析，使用粪便进行生化预测技术，具有非侵入性方法的优势，不会耗尽已经有限的血量的低胎龄婴儿。格雷戈里博士将在W.Allan Walker医学博士的指导下，培训与胃肠道疾病发病机制的人类微生物群相关的科学方法。她将在布鲁斯·克里斯托博士的指导下进行代谢和生物信息学分析，以预测疾病。最后，Gregory博士将在临床环境中接受Linda Van Marter医学博士和公共卫生硕士的指导，她将在那里收集生物样本，开发一个用于未来分析的样本库，并对与NEC相关的临床因素进行流行病学调查。该指导团队已被选中，在胃肠道疾病、营养、微生物组分析、代谢组学和尖端新生儿研究等领域拥有多样化的研究专业知识。总之，应聘者将在世界级的研究环境中与经验丰富的导师合作。她将在她的研究和培训目标上取得成功。 相关性：尽管新生儿重症监护取得进展，早产儿存活率显著提高，坏死性小肠结肠炎仍然是早产最重要的并发症之一。疾病预测是以患者为中心的研究中的一个优先领域，它将彻底改变我们照顾患者的方式，并改善人类健康。需要新的范式来理解NEC的发病机制，这将有助于我们预测这种疾病，并反过来改善对早产儿的护理。

DESCRIPTION (provided by applicant): The candidate, Katherine E. Gregory, PhD, RN, aims to become an independent clinical investigator who will lead her field in an innovative program of patient-oriented research. Dr. Gregory's program of research will generate new models of disease pathogenesis and prediction using cutting-edge biochemical analysis (i.e. microbiome) and bioinformatic prediction strategies (i.e. metabolomics). As part of her research training and experience to date, she has identified clinical predictors of necrotizing enterocolitis (NEC) in premature infants. This work has extended knowledge of antecedents of NEC well beyond prematurity and demographics. Dr. Gregory will remain focused on NEC, one of the major unsolved problems of neonatal care, the most common gastrointestinal emergency experienced by premature infants, and the leading reason for aberrant nutrition, growth and neurodevelopment in premature infants. New paradigms are needed to understand NEC etiology and pathobiology, which will aid in our prediction of this and other diseases. The central hypothesis of the research proposed is that NEC may be predicted in a population of extremely low gestational age neonates using non-serum based biologic sample (i.e. urine and stool). The use of urine for biomarker assays and stool for biochemical prediction techniques has the advantage of a noninvasive approach that would not deplete the low gestational age infant of an already limited blood volume. Dr. Gregory will train in the scientific methods related to the human microbiome of gastrointestinal disease pathogenesis under the mentorship of W. Allan Walker, MD. She will work under the mentorship of Bruce Kristal, PhD in conducting the metabolomic and bioinformatic analyses for the purpose of disease prediction. Finally, Dr. Gregory will be mentored by Linda Van Marter, MD, MPH in the clinical setting where she will collect biologic sample, develop a specimen bank for future analysis, and conduct an epidemiologic investigation of clinical factors related to NEC. This mentorship team has been selected for a diversity of research expertise in areas including gastrointestinal disease, nutrition, microbiome analysis, metabolomics, and cutting-edge neonatal research. In sum, the candidate will work with seasoned mentors in a world-class research environment. She will be successful in her research and training aims. RELEVANCE: Despite advances in neonatal intensive care and significant gains in premature infant survival, necrotizing enterocolitis remains one of the most significant complications of premature birth. Disease prediction, a priority area in patient-oriented research, will revolutionize how we take care of patients and improve human health. New paradigms are needed to understand the pathogenesis of NEC, which will aid in our ability to predict this disease and in turn improve care for premature infants.