Role of Gardnerella vaginalis in the Urinary Tract

阴道加德纳菌在尿道中的作用

• 批准号: 9912142
• 负责人: Nicole Marie Gilbert
• 金额: $ 11.17万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-25 至 2022-04-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9912142
• 关键词: Abscess; Acute Renal Failure with Renal Papillary Necrosis; Address; Affect; Agonist; Antibiotic Resistance; Apoptosis; Apoptotic; Area; Automobile Driving; Bacteria; Bacterial Infections; Bacterial Vaginosis; Biological Factors; Biological Markers; Biometry; Bladder; Caspase Inhibitor; Cells; Cellular Stress; Chemicals; Clinical; Clinical Research; Clinical Sciences; Coitus; Communicable Diseases; Data; Disease; Educational process of instructing; Epithelial; Epithelium; Escherichia coli; Exposure to; Faculty; Frequencies; Gardnerella vaginalis; Genitourinary system; Goals; Grant; Human; Immune; Immune response; Infection; Infective cystitis; Inflammatory Response; Inflammatory Response Pathway; Institutes; Instruction; Interview; Journals; Kidney; Laboratories; Language; Learning; Life; Manuscripts; Medical Research; Mentored Research Scientist Development Award; Mentors; Modeling; Molecular; Mus; Nested Case-Control Study; Nuclear Orphan Receptor; Occupations; Peer Review; Population; Pregnancy; Prevalence; Procedures; Proteins; Publications; Recurrence; Research; Research Design; Research Ethics; Research Personnel; Research Proposals; Research Training; Risk; Risk Factors; Role; Specimen; Symptoms; Systemic infection; Testing; Tissues; Training; Training Activity; Transcript; Translating; Translational Research; United States National Institutes of Health; Universities; Urethra; Urinary tract; Urinary tract infection; Urine; Urologic Diseases; Urology; Urothelium; Vagina; Washington; Woman; Writing; acute infection; base; career; career development; career networking; clinical center; co-infection; cost; cytokine; experimental study; infection risk; innovation; kidney infection; medical schools; meetings; member; microbiota; mouse model; neutrophil; novel; pathogen; recurrent infection; response; sexually active; skills; transcriptome sequencing; vaginal infection; vaginal microbiota

ABSTRACT The overall goal of this proposal is to provide me with the skills and expertise necessary to launch my career in translational medical research in the field of urologic disease, particularly bacterial infections of the urinary tract. To achieve this goal, I will use the K01 mechanism to meet the following training objectives: Objective 1: Generate innovative data for publication in highly regarded peer-reviewed journals. Recurrent urinary tract infections (UTI) disproportionately affect women and are common, costly and sometimes life threatening. Escherichia coli is the most frequent causative agent of UTI, and has been shown in mouse models to establish antibiotic-resistant tissue reservoirs that persist long after acute infection of the bladder lumen is resolved. Bacterial emergence from such reservoirs has long been regarded as one likely origin of recurrent infections in humans. We have shown in a novel mouse model that Gardnerella vaginalis, a common member of the urogenital microbiota, causes E. coli to emerge from bladder reservoirs and initiate a recurrent UTI episode. The experiments outlined in this research plan test the hypothesis that G. vaginalis induces UTI recurrence by damaging the bladder epithelium (Aim 1) and modulating the host inflammatory response (Aim 2). These studies will increase our understanding of the mechanisms driving UTI recurrence and have the potential to identify G. vaginalis as a biomarker of risk in susceptible women. Objective 2: Gain expertise in performing translational research. I will engage in training activities, including seminars and didactic coursework offered by the NIH Clinical Center and through the Clinical Research Training Center (CRTC) of the Institute for Clinical and Translational Sciences (ICTS) at Washington University School of Medicine. This instruction will teach me the language and procedures of clinical study design and execution and is essential for me to meet my goal of leading a transdisciplinary team doing T1 clinical research. With guidance from my co-mentors and the Research Design and Biostatistics Group of the ICTS, I will hone my skills in this area by performing a nested case-control study that seeks to confirm the findings of our mouse model in human clinical specimens. Objective 3: Develop my professional abilities and grow my professional network. Washington University has a wealth of career development mechanisms offered through the Center for the Integration of Research, Teaching, and Learning, the Offices of Postgraduate and Faculty Affairs and the CRTC. I will attend seminars and courses on research ethics, scientific manuscript and grant writing, academic job interviewing, laboratory finances and management. Additionally, I will attend instructive seminars at national meetings on urology and infectious diseases, where I will present my research findings and network and build collaborative relationships with leading researchers in the field. I have assembled a mentoring committee that includes leaders in the field of UTI research, which will evaluate the completion of both my scientific and career development milestones and facilitate my transition to an independent investigator.

抽象的 该提案的总体目标是为我提供开展职业生涯所需的技能和专业知识 泌尿系统疾病领域的转化医学研究，特别是泌尿道细菌感染 道。为了实现这个目标，我将利用K01机制来实现以下培训目标： 目标1： 生成创新数据，以便在备受推崇的同行评审期刊上发表。尿路复发 感染（UTI）对女性的影响尤为严重，而且很常见、成本高昂，有时甚至危及生命。 大肠杆菌是尿路感染最常见的病原体，并已在小鼠模型中显示 建立耐抗生素的组织储库，该储库在膀胱腔急性感染后仍持续很长时间 解决了。长期以来，此类水库中细菌的出现一直被认为是复发性传染病的可能根源之一。 人类感染。我们在一种新颖的小鼠模型中证明了阴道加德纳菌（Gardnerella vaginalis），一种常见的成员 泌尿生殖微生物群的破坏，导致大肠杆菌从膀胱储库中出现并引发复发性尿路感染 插曲。本研究计划中概述的实验检验了阴道加德纳菌诱发尿路感染的假设 通过损伤膀胱上皮（目标 1）和调节宿主炎症反应（目标 2）。这些研究将加深我们对尿路感染复发机制的理解，并具有 确定阴道加德纳菌作为易感女性风险生物标志物的潜力。目标 2：获得以下方面的专业知识 进行转化研究。我将参加培训活动，包括研讨会和教学 由 NIH 临床中心和临床研究培训中心 (CRTC) 提供的课程 华盛顿大学医学院临床与转化科学研究所 (ICTS)。这 指导将教会我临床研究设计和执行的语言和程序，这是必不可少的 让我能够实现领导跨学科团队进行 T1 临床研究的目标。在我的指导下 共同导师和 ICTS 的研究设计和生物统计小组，我将通过以下方式磨练我在该领域的技能 进行巢式病例对照研究，旨在证实我们的小鼠模型在人类临床中的发现 标本。目标3：发展我的专业能力并扩大我的专业网络。华盛顿 大学通过融合中心提供丰富的职业发展机制 研究、教学和学习、研究生和教师事务办公室以及 CRTC。我会参加 关于研究伦理、科学手稿和资助写作、学术工作面试的研讨会和课程， 实验室财务和管理。此外，我将参加全国会议上的指导性研讨会 泌尿学和传染病，我将在那里展示我的研究成果和网络并建立协作 与该领域领先研究人员的关系。我组建了一个指导委员会，其中包括 UTI 研究领域的领导者，这将评估我的科学和职业生涯的完成情况 发展里程碑并促进我向独立调查员的过渡。