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.

项目总结/摘要 Thuy多安博士的K 08申请，哲学博士、描述了一个旨在提高她的五年战略， 研究和专业技能，职业目标是成为一名独立的临床科学家， 对眼部感染性和炎症性疾病的了解，并改善其治疗。 感染性葡萄膜炎和眼部感染是全球眼部发病和失明的主要原因。而 及时和准确的诊断对于改善视力结果至关重要，但明确的诊断往往不是 考虑到在易患眼部感染的因素方面存在重大知识差距， 眼科可用的诊断测试。这一提议的核心假设是，细菌和病毒 眼表面的成分与眼的健康和疾病有关。该项目的目标是 了解这种潜在的病原体储存库，眼表微生物组和病毒组，并确定 与眼部感染有关的传染性病原体。我们建议提高眼分子的能力， 本发明的目的在于提供诊断方法，并增强对眼部感染的发病机理的理解，其目的如下。 第一个目标将评估使用基于下一代测序（NGS）的方法作为可行的临床 眼部感染的诊断测试。这些实验将直接比较NGS与目前的常规 使用存档的眼内样本进行分子诊断。然后将预先收集的水样 评估潜在病原体。第二个目标将描述抗生素对细菌的影响， 和病毒群落使用的样本收集在一个大型随机对照试验。这些研究有 有可能改善诊断模式并指导针对眼部感染的靶向干预。 我致力于在眼科领域发展一个以临床研究为导向的职业生涯， 学术机构，并了解需要追求额外的正式培训和指导。关键 职业发展计划的组成部分包括：（1）眼表的实验室检查 微生物组，病毒组和眼部感染性疾病的原因;（2）来自多学科小组的指导， 科学家和临床科学家，具有先进分子技术，生物统计学和临床 试验设计;（3）正式教学，以扩大分子生物学，生物统计学和临床微生物学 知识;（4）R 01应用的数据收集;以及（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经成立，以确保 走向独立。职业发展计划将在大学进行。 加州，旧金山弗朗西斯科，它提供了一个特殊的环境进行这项研究，包括国家- 最先进的设施和世界级的科学家支持社区，这些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

Evaluation of Metagenomic Deep Sequencing as a Diagnostic Test for Infectious Keratitis.

评估宏基因组深度测序作为感染性角膜炎的诊断测试。

• DOI: 10.1016/j.ophtha.2020.07.030
• 发表时间: 2021-03
• 期刊: Ophthalmology
• 影响因子: 13.7
• 作者: Lalitha P;Prajna NV;Sikha M;Gunasekaran R;Hinterwirth A;Worden L;Chen C;Zhong L;Liu Z;Lietman TM;Seitzman GD;Doan T
• 通讯作者: Doan T