The association between the urine microbiome, the host immune response and urinary symptoms in children with spina bifida

凯瑟琳·福斯特，医学博士，医学硕士，医院医学儿科医生，她的首要职业目标是成为 世界公认的神经性膀胱炎儿童尿路感染的领导者。 研究：尽管尿路感染(UTI)对儿童健康结局的重要性 对于神经性膀胱，目前还没有方法可以准确地诊断这一人群中的尿路感染。这 提案将开始填补这一空白。这项提案的目标是确定哪些儿童应该接受测试 UTI，开发一种使用小鼠模型对UTI高度特异的诊断方法，并将这些结果转化为 一群儿童飞行员。这些目标将通过完成以下具体目标来实现：1) 开发一种基于临床特征的算法来确定脊柱儿童发生尿路感染的可能性 2)确定尿液微生物多样性与尿液生物标志物之间的关系。 神经病理性膀胱；3)探讨尿路感染与尿菌群多样性和/或尿液的关系 脊柱裂儿童的生物标志物。目标1将通过使用来自多机构的数据来完成 保留初始肾功能的泌尿外科治疗脊柱裂患儿的方案研究。 AIM 2将同时使用神经性膀胱的遗传和外科小鼠模型。在目标3中，尿路生物群和 将对有症状的脊柱裂儿童进行尿液生物标志物的检测。 职业发展：福斯特博士与她的导师卡尔·贝茨博士和纳德·谢赫博士一起， 在她之前的培训基础上制定了职业发展计划，旨在解决以下领域 她需要额外的培训：获得关于小鼠膀胱研究和遗传模型的更多知识 膀胱疾病，创造和维护一个小鼠群体，获得尿动力学解释的经验 数据，发展生物信息学方法的工作知识，以分析16S rRNA测序数据，以及 在招募和收集一群儿科患者的预期尿样方面培养专业知识。 拟议的培训计划将为Forster博士提供必要的技能，以验证这项工作的结果。 环境：这项研究将在匹兹堡儿童医院内进行。建议数 职业发展计划利用匹兹堡大学和 CHP，包括微生物组和医学中心，以及国家认可的研讨会和课程。 摘要：这项拟议的创新性研究将扩大尿路感染诊断的证据基础。 患有脊柱裂的儿童。与NIDDK的使命相一致，这项工作将对 改善患有神经性膀胱的儿童的健康。福斯特博士的研究和临床培训 研究经验和敬业的指导团队使她成为从事这项研究的理想人选。这 获奖将有助于福斯特博士继续发展成为一名独立的调查员 优化神经性膀胱患儿护理及预后的研究。

Catherine Forster, MD, MS is a pediatrician in hospital medicine whose overarching career goal is to be a world-recognized leader on UTIs in children with neuropathic bladder. Research: Despite the importance of urinary tract infections (UTIs) to health outcomes in children with neuropathic bladders, there are currently no methods to accurately diagnose UTIs in this population. This proposal will begin to fill that gap. The goals of this proposal are to identify children who should be tested for a UTI, develop a highly specific diagnostic method for UTI using mouse models, and translate these results into a pilot cohort of children. These goals will be attained through completion of the following specific aims: 1) Develop an algorithm based on clinical characteristics to determine the probability of UTI in children with spina bifida; 2) Identify the relationship between urine microbial diversity and urinary biomarkers in mouse models of neuropathic bladder; and 3) Explore the association between UTI and urobiome diversity and/or urine biomarkers in children with spina bifida. Aim 1 will be completed through use of data from the multi-institutional Urologic Management to Preserve Initial Renal Function Protocol for Young Children with Spina Bifida study. Aim 2 will use both genetic and surgical mouse models of neuropathic bladder. In Aim 3, the urobiome and urine biomarkers will be measured in symptomatic children with spina bifida. Career Development: Together with her mentors, Dr. Carl Bates and Dr. Nader Shaikh, Dr. Forster has created a career development plan built upon her prior training that is designed to address the areas where she requires additional training: Gain additional knowledge around mouse bladder studies and genetic models of bladder disease, create and maintain a mouse colony, gain experience with interpretation of urodynamic data, develop working knowledge of bioinformatic approaches to analyze 16S rRNA sequencing data, and develop expertise with recruiting and collecting prospective urine samples from a cohort of pediatric patients. The proposed training plan will provide Dr. Forster with the necessary skills to validate the results of this work. Environment: This research will take place within the Children’s Hospital of Pittsburgh (CHP). The proposed career development plan utilizes the intellectual resources available through the University of Pittsburgh and CHP, including the Center for Microbiome and Medicine, and nationally recognized seminars and courses. Summary: This proposed innovative research will expand the evidence base for the diagnosis of UTI in children with spina bifida. Aligned with NIDDK’s mission, this work will be an important contribution to improving the health of children with neuropathic bladders. Dr. Forster's research and clinical training, prior research experiences, and dedicated mentorship team make her ideally suited to pursue this research. This award will facilitate Dr. Forster’s continued development into an independent investigator in the conduct of research of the optimizing the care and outcomes of children with neuropathic bladders.