Ocular Surface Microbiome, Virome, and Pathogens in Ophthalmic Disease and Health

眼科疾病与健康中的眼表微生物组、病毒组和病原体

• 批准号: 9980409
• 负责人: Thuy A Doan
• 金额: $ 23.91万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9980409
• 关键词: Anterior uveitis; Antibiotic Therapy; Antibiotics; Aqueous Humor; Archives; Azithromycin; Bioinformatics; Biological Assay; Biometry; Blindness; California; Clinical; Clinical Microbiology; Clinical Research; Clinical Trials Design; Communicable Diseases; Communities; Complement; Complex; Consumption; Corneal Ulcer; Data Collection; Detection; Development; Development Plans; Diagnosis; Diagnostic; Diagnostic tests; Disease; Doctor of Medicine; Doctor of Philosophy; Endophthalmitis; Environment; Etiology; Eye Infections; Foundations; Future; Goals; Gold; Health; Herpesviridae; Human; Infectious Agent; Inflammatory; Institution; Institutional Review Boards; Intervention; Investigation; Knowledge; Laboratories; Liquid substance; Mentors; Mentorship; Microbe; Molecular; Molecular Biology; Morbidity - disease rate; Niger; Ophthalmology; Organism; Outcome; Pathogenesis; Patients; Performance; Placebos; Polymerase Chain Reaction; Postoperative Period; Predisposing Factor; Public Health; Randomized Controlled Trials; Reaction; Research; Sampling; San Francisco; Scientist; Sensitivity and Specificity; Shotguns; Specimen; Suggestion; Surface; System; Techniques; Testing; Time; Toxoplasma; Training; Uncertainty; Universities; Uveitis; Viral; Virus; Virus Diseases; Visual; Work; accurate diagnosis; aqueous; bacterial community; base; career; career development; clinical diagnostics; co-infection; conjunctiva; deep sequencing; design; experimental study; improved; innovation; metagenomic sequencing; microbiome; microorganism interaction; molecular diagnostics; multidisciplinary; next generation sequencing; novel; ocular surface; particle; pathogen; prevent; prospective; rRNA Genes; response; skills; success; virome

PROJECT SUMMARY/ABSTRACT This K08 application for Thuy Doan, M.D., Ph.D., describes a five year strategy designed to enhance her research and professional skills with the career goal of becoming an independent clinician scientist advancing the understanding of ocular infectious and inflammatory diseases and improving their treatment. Infectious uveitis and ocular infections are a major cause of ocular morbidity and blindness worldwide. While timely and accurate diagnosis is crucial for improved visual outcomes, a definitive diagnosis is often not possible given the significant knowledge gap in factors predisposing to eye infections and the limitations of available diagnostic tests in ophthalmology. The core hypothesis of this proposal is that the bacterial and viral constituents of the ocular surface are involved in ocular health and disease. The goal of this project is to understand this potential pathogen reservoir, the ocular surface microbiome and virome, and to identify infectious agents involved in ocular infections. We propose to advance the capabilities of ocular molecular diagnostics and enhance the understanding of the pathogenesis of ocular infections with the following aims. The first aim will evaluate the use of a next-generation sequencing (NGS)-based approach as a viable clinical diagnostic test for ocular infections. These experiments will directly compare NGS to the current conventional molecular diagnostics using archived intraocular samples. Prospectively collected aqueous samples will then be assessed for potential pathogens. The second aim will characterize the effects of antibiotics on the bacterial and viral communities using samples collected in a large randomized controlled trial. These studies have the potential to improve the diagnostic paradigm and guide targeted interventions for ocular infections. I am committed to developing a clinical research-oriented career in the field of ophthalmology at a major academic institution and understand the need to pursue additional formal training and mentorship. Key components of the career development plan include: (1) laboratory investigations of the ocular surface microbiome, virome, and causes of ocular infectious diseases; (2) mentorship from a multidisciplinary group of scientists and clinician scientists with expertise in advanced molecular techniques, biostatistics, and clinical trial designs; (3) formal didactics to expand molecular biology, biostatistics, and clinical microbiology knowledge; (4) data collection for R01 application; and (5) planned transition to independence including professional development. A scientific advisory and mentorship committee has been assembled to assure progression toward independence. The career development plan will be carried out at the University of California, San Francisco, which provides an exceptional environment to conduct this research, including state- of-the-art facilities and a world-class and supportive community of scientists all critical to my future success.

项目摘要/摘要 这项K08申请申请Thuy Doan，M.D。，博士，描述了旨在增强她的五年策略 研究和专业技能，其职业目标是成为一名独立临床医生的发展 对眼部传染和炎症性疾病的理解并改善了治疗。 感染性葡萄膜炎和眼部感染是全世界眼部发病率和失明的主要原因。尽管 及时，准确的诊断对于改善视觉结果至关重要，确定的诊断通常不是 考虑到易受眼感染的因素的明显知识差距，可能 眼科中可用的诊断测试。该提议的核心假设是细菌和病毒 眼表的成分参与眼部健康和疾病。这个项目的目标是 了解这种潜在的病原体储层，眼表面微生物组和病毒瘤，并鉴定 参与眼部感染的传染剂。我们建议提高眼分子的能力 诊断和增强对眼部感染的发病机理的理解。 第一个目的将评估下一代测序（NGS）的使用作为可行的临床 眼部感染的诊断测试。这些实验将直接将NG与当前的常规进行比较 分子诊断使用存档的眼内样品。前瞻性收集的水样将 评估潜在病原体。第二个目标将表征抗生素对细菌的影响 使用大型随机对照试验中收集的样品和病毒群落。这些研究具有 改善眼部感染的诊断范式和指导靶向干预措施的潜力。 我致力于在一个专业的眼科领域发展面向临床研究的职业 学术机构并了解需要进行额外的正式培训和指导。钥匙 职业发展计划的组成部分包括：（1）实验室研究眼表 微生物组，病毒瘤和眼部传染病的原因； （2）来自多学科小组的指导 具有高级分子技术，生物统计学和临床​​方面的专业知识的科学家和临床医生科学家 试用设计； （3）正式的教学法扩展分子生物学，生物统计学和临床​​微生物学 知识; （4）R01应用程序的数据收集； （5）计划向独立过渡，包括 专业发展。一个科学咨询和指导委员会已组装以确保 向独立发展。职业发展计划将在大学进行 加利福尼亚州旧金山，提供了一个特殊的环境来进行这项研究，包括国家 艺术设施和一个世界一流和支持的科学家社区都对我未来的成功至关重要。

项目成果

Macrolide Resistance and Longer-Term Assessment of Azithromycin in MORDOR I. Reply.

MORDOR I 中阿奇霉素的大环内酯耐药性和长期评估。回复。

• DOI: 10.1056/nejmc1910014
• 发表时间: 2019
• 期刊: The New England journal of medicine
• 作者: Lietman,ThomasM;Doan,Thuy;Keenan,JeremyD
• 通讯作者: Keenan,JeremyD

Poultry Ownership and Genetic Antibiotic Resistance Determinants in the Gut of Preschool Children.

学龄前儿童肠道中的家禽饲养和遗传性抗生素耐药性决定因素。

• DOI: 10.4269/ajtmh.20-1384
• 发表时间: 2021
• 期刊: The American journal of tropical medicine and hygiene
• 作者: Brogdon,JessicaM;Sié,Ali;Dah,Clarisse;Ouermi,Lucienne;Coulibaly,Boubacar;Lebas,Elodie;Zhong,Lina;Chen,Cindi;Lietman,ThomasM;Keenan,JeremyD;Doan,Thuy;Oldenburg,CatherineE
• 通讯作者: Oldenburg,CatherineE

Comprehensive pathogen detection for ocular infections.

• DOI: 10.1016/j.jcv.2021.104759
• 发表时间: 2021-03
• 期刊: Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
• 作者: Doan T;Sahoo MK;Ruder K;Huang C;Zhong L;Chen C;Hinterwirth A;Lin C;Gonzales JA;Pinsky BA;Acharya NR
• 通讯作者: Acharya NR

Gut Resistome of Preschool Children After Prolonged Mass Azithromycin Distribution: A Cluster-randomized Trial.

• DOI: 10.1093/cid/ciab485
• 发表时间: 2021-10-05
• 期刊: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
• 作者: Arzika AM;Maliki R;Abdou A;Mankara AK;Harouna AN;Cook C;Hinterwirth A;Worden L;Zhong L;Chen C;Ruder K;Zhou Z;Lebas E;O'Brien KS;Oldenburg CE;Le V;Arnold BF;Porco TC;Keenan JD;Lietman TM;Doan T
• 通讯作者: Doan T

High-throughput sequencing of pooled samples to determine community-level microbiome diversity.

对合并样本进行高通量测序以确定群落水平的微生物组多样性。

• DOI: 10.1016/j.annepidem.2019.09.002
• 发表时间: 2019
• 期刊: Annals of epidemiology
• 影响因子: 5.6
• 作者: Ray,KathrynJ;Cotter,SunY;Arzika,AhmedM;Kim,Jessica;Boubacar,Nameywa;Zhou,Zhaoxia;Zhong,Lina;Porco,TravisC;Keenan,JeremyD;Lietman,ThomasM;Doan,Thuy
• 通讯作者: Doan,Thuy