Non-Sjogren's Syndrome-and Sjogren's Syndrome-related Keratoconjunctivitis SICCA: A Spectrum of Inflammatory Dry Eye

非干燥综合征和干燥综合征相关角结膜炎 SICCA：炎症性干眼症谱系

• 批准号: 9322864
• 负责人: John Alexander Gonzales
• 金额: $ 25.18万
• 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: 2016-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9322864
• 关键词: Affect; Autoimmune Diseases; Autoimmune Process; Award; Bioinformatics; Biometry; Biopsy; California; Chronic; Classification; Clinical; Clinical Research; Clinical Trials; Collection; Confocal Microscopy; Cornea; Corneal Ulcer; Critical Care; Data; Databases; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Dryness; Environment; Epidemiologic Methods; Epidemiology; Esthesia; European; Exhibits; Foreign Bodies; Foundations; Funding; Future; Gene Expression; Gene Expression Profile; Genetic screening method; Genetic study; Genomics; Goals; Gold; Grant; Guidelines; Harvest; Health; High-Throughput Nucleotide Sequencing; Incidence; Individual; Inflammation; Inflammatory; Injury; International; K-Series Research Career Programs; Keratoconjunctivitis; Keratoconjunctivitis Sicca; Labial Salivary Gland; Lacrimal gland structure; Lead; Learning; Lung; Lung diseases; Lymphocyte; Malignant Neoplasms; Medicine; Mental Depression; Mentored Patient-Oriented Research Career Development Award; Mentors; Molecular; Motivation; Nerve; Nerve Plexus; Ophthalmology; Outcome; Pain; Participant; Pathogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacotherapy; Photophobia; Production; Prospective cohort study; Quality of life; Questionnaires; Randomized Clinical Trials; Registries; Research; Research Personnel; Research Priority; Rewards; Rheumatism; Rheumatoid Factor; Risk; Salivary Glands; San Francisco; Science; Seminal; Serological; Serum; Severities; Signal Transduction; Sjogren' s Syndrome; Specialist; Staining method; Stains; Standardization; Steroids; Symptoms; Technology; Testing; Trachoma; Ulcer; United States National Institutes of Health; Universities; Uveitis; aqueous; biobank; career development; cohort; data registry; epidemiology study; experience; eye dryness; follow-up; genetic signature; high risk; indexing; mid-career faculty; mortality; neuropathology; orofacial; painful neuropathy; patient oriented research; peripheral blood; prevent; professor; profiles in patients; public health relevance; skills; success; systemic autoimmune disease; transcriptome sequencing; treatment trial

NON-SJÖGREN'S SYNDROME AND SJÖGREN'S SYNDROME KERATOCONJUNCTIVITIS SICCA: A SPECTRUM OF INFLAMMATORY DRY EYE ABSTRACT This is an application for a mentored K23 career development award to Dr. John A. Gonzales, a uveitis specialist at The F.I. Proctor Foundation at the University of California, San Francisco. Dr. Gonzales is establishing himself as an investigator in patient-oriented research focused on ocular inflammatory conditions including keratoconjunctivitis sicca and uveitis. This K23 Award will provide Dr. Gonzales the support necessary to complete the following goals: (1) to become skilled in epidemiology research by utilizing the Sjögren's International Collaborative Clinical Alliance (SICCA) Registry's wealth of data; (2) to understand the nuances and utility of high throughput sequencing technology to; (3) to learn and utilize advanced statistical and epidemiology methods necessary for success in clinical studies; and (4) to develop the skills needed to transition to an independent investigator. To achieve these goals Dr. Gonzales has assembled a team of mentors comprised of the following experts: • Dr. Tom Lietman, a Professor in both the Departments of Ophthalmology and Epidemiology and Biostatistics at UCSF. Dr. Lietman has been awarded NIH-funded grants for seminal randomized clinical trials in infectious and inflammatory ocular diseases including Eliminating trachoma with repeat mass drug treatment, the Steroids for Cornea Ulcers Trial, and the Mycotic Ulcer Treatment Trial. • Dr. Caroline Shiboski, Professor in the Department of Orofacial Sciences is a Sjögren's syndrome expert. She has extensive experience leading the SICCA study eading an international effort to obtain definitive approval from both ACR and the European League Against Rheumatism (EULAR) of a final set of criteria to be used for entry into Sjögren's syndrome clinical trials • Dr. Laura Koth, Associate Professor in the Department of Medicine in the Division of Pulmonary and Critical Care Medicine. Dr. Koth is an expert in genomics and bioinformatics utilizing high-throughput sequencing to characterize autoimmune pulmonary disease. The research proposed herein seeks to accomplish the following: (1) to examine how non-Sjögren's and Sjögren's-related keratoconjunctivitis impact quality of life, depression, and mortality; (2) to identify accompanying features of corneal neuropathology and neuropathic pain when patients convert from non- Sjögren's keratoconjunctivitis to Sjögren's syndrome; and (4) to characterize Sjögren's syndrome on a gene expression level. This research will form the basis for an R01 application before the end of the K award. Dr. Gonzales's passion and motivation for the proposed project, the environment at the Proctor Foundation and at UCSF, and the support of his mentors will set the stage for a rigorous and rewarding career development into an independent researcher.

非Sjgren综合征和Sjgren综合征的角膜结膜炎 炎性干眼的光谱 摘要 这是向John A博士申请辅导K23职业发展奖的申请。冈萨雷斯，葡萄膜炎 F.I.的专家弗朗西斯科加州大学普罗克特基金会。冈萨雷斯医生 确立了自己作为以患者为导向的研究，专注于眼部炎症状况的研究者的地位 包括干燥性角膜结膜炎和葡萄膜炎。这个K23奖将为冈萨雷斯博士提供支持 必须完成以下目标： (1)通过利用舍格伦国际合作临床研究中心， 联盟（SICCA）注册中心的丰富数据;（2）了解高吞吐量的细微差别和实用性 测序技术;（3）学习和利用先进的统计和流行病学方法， 在临床研究中取得成功;（4）发展过渡到独立研究者所需的技能。 为了实现这些目标，冈萨雷斯博士组建了一个由以下专家组成的导师团队： ·Tom Lietman博士，眼科和流行病学系教授， 加州大学旧金山分校的生物统计学。Lietman博士已获得NIH资助的赠款，用于 感染性和炎症性眼病的临床试验，包括重复消除沙眼 大规模药物治疗、类固醇治疗角膜溃疡试验和肌溃疡治疗试验。 ·Caroline Shiboski博士，口腔颌面科学系教授，患有舍格伦综合征 专家她在领导SICCA研究方面拥有丰富的经验， ACR和欧洲反风湿联盟（EULAR）最终批准了决赛 用于进入干燥综合征临床试验的一组标准 ·Laura Koth博士，肺和肺科医学系副教授 重症监护医学。Koth博士是基因组学和生物信息学方面的专家， 测序以表征自身免疫性肺病。 本文提出的研究旨在实现以下目标：（1）检查非Sjögren和 干燥相关性角膜结膜炎影响生活质量、抑郁和死亡率;（2）识别 伴随的角膜神经病理学和神经性疼痛的特点，当患者从非- 干燥角结膜炎与干燥综合征的关系;（4）干燥综合征的基因特征 表达水平。 这项研究将成为K奖结束前R 01申请的基础。冈萨雷斯医生的热情 和动机的拟议项目，在普罗克特基金会和加州大学旧金山分校的环境， 他的导师的支持将为一个严格和有益的职业发展成为一个独立的阶段 研究员