Biochemical Predictors of Necrotizing Enterocolitis

描述（由申请人提供）：候选人Katherine E. Gregory，博士，注册护士，目标是成为一名独立的临床研究者，她将在一个以患者为导向的创新研究项目中领导她的领域。Gregory博士的研究项目将使用尖端的生化分析（即微生物组）和生物信息学预测策略（即代谢组学）产生疾病发病机理和预测的新模型。作为她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。这项工作已经扩展了NEC的前身的知识远远超出了早产和人口统计学。Gregory博士将继续专注于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，这将有助于我们预测这种疾病和其他疾病。该研究提出的中心假设是，NEC可以在极低胎龄新生儿中使用非血清生物样本（即尿液和粪便）进行预测。使用尿液进行生物标志物测定，使用粪便进行生化预测技术具有无创方法的优点，不会耗尽低胎龄婴儿已经有限的血容量。Gregory博士将在W. Allan Walker， MD的指导下学习与胃肠道疾病发病机制的人类微生物组相关的科学方法。她将在Bruce Kristal博士的指导下进行以疾病预测为目的的代谢组学和生物信息学分析。最后，Gregory博士将在临床环境中接受Linda Van Marter，医学博士，公共卫生硕士的指导，她将收集生物样本，为未来的分析开发一个标本库，并对NEC相关的临床因素进行流行病学调查。该指导团队在胃肠道疾病、营养、微生物组分析、代谢组学和前沿新生儿研究等领域拥有丰富的研究专业知识。总之，候选人将在世界一流的研究环境中与经验丰富的导师一起工作。她将成功实现她的研究和培训目标。

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.