The Molecular Basis of Pseudoexfoliation Syndrome

假性剥脱综合征的分子基础

• 批准号: 7114343
• 负责人: PRATAP CHALLA
• 金额: $ 19.17万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7114343
• 关键词: age difference; blood chemistry; clinical research; comorbidity; family genetics; functional /structural genomics; gene expression; genetic disorder; genetic susceptibility; genotype; glaucoma; high performance liquid chromatography; human subject; hyperproteinemia; linkage mapping; microarray technology; molecular pathology; nucleic acid probes; nucleic acid sequence; phenotype; polymerase chain reaction; protein metabolism disorder; racial /ethnic difference; sequence tagged sites; single strand conformation polymorphism; southern blotting

DESCRIPTION (provided by applicant): This grant proposal outlines a five-year training program for the development of an academic career in molecular biology. The principal investigator is a fellowship-trained clinician who proposes to expand and diversify his scientific ability through intensive coursework and reentered research training. The didactic portion of this program will consist of graduate level coursework at Duke University and regular sessions with the proposed mentors, Drs Klintworth and Bowes Rickman. Dr Klintworth is director of the Ophthalmic Genetics Center at Duke University and has expertise in studying genetically determined diseases of the eye. Dr Bowes Rickman is an Assistant Professor of Ophthalmology and Cell Biology and has expertise in characterizing mRNAs and proteins in ocular disorders. The proposed research is to investigate the molecular mechanisms that are associated with the development of pseudoexfoliation syndrome (PEX) and pseudoexfoliation syndrome with glaucoma (PEX-G) using gene array technologies. PEX is an idiopathic systemic disease characterized by fibrillar deposits in multiple ocular and non-ocular tissues. PEX is the most common identifiable cause of open angle glaucoma worldwide and is phenotypically distinct from primary open angle glaucoma. Growing evidence suggests that PEX is a late onset inherited disorder. Despite the prevalence of PEX and PEX-G little is known about their underlying molecular mechanisms. In short, we propose to: 1) Identify genes or ESTs involved in the pathogenesis of PEX using gene array technologies 2) Characterize/deduce gene sequences 3) Identify differences in gene expression between PEX and PEX-G and 4) Ascertain and recruit additional PEX patients and families. These investigations are critical to understanding the molecular basis of PEX and any modifying genetic factors that would predispose to the development of glaucoma. The Ophthalmology department at Duke University is an ideal setting for training physician-scientists and has an established track record of strong support for promising clinician-scientists.

描述（由申请人提供）：此拨款提案概述了分子生物学学术生涯发展的五年培训计划。首席研究员是一名接受过奖学金培训的临床医生，他建议通过强化课程和重新进入研究培训来扩展和多样化他的科学能力。该计划的教学部分将包括杜克大学研究生水平的课程，以及与拟议导师Klintworth博士和Bowes Rickman博士的定期会议。Klintworth博士是杜克大学眼科遗传学中心的主任，在研究由基因决定的眼部疾病方面具有专长。Bowes Rickman博士是眼科学和细胞生物学助理教授，在眼部疾病的mrna和蛋白质表征方面拥有专业知识。本研究拟利用基因阵列技术研究假表皮脱落综合征（PEX）和假表皮脱落综合征伴青光眼（PEX- g）发生的分子机制。PEX是一种特发性全身性疾病，以眼部和非眼部组织中的纤维沉积为特征。PEX是开角型青光眼最常见的病因，在表型上与原发性开角型青光眼不同。越来越多的证据表明，PEX是一种晚发性遗传疾病。尽管PEX和PEX- g普遍存在，但对其潜在的分子机制知之甚少。总之，我们建议：1)利用基因阵列技术鉴定参与PEX发病机制的基因或ESTs； 2)表征/推断基因序列；3)鉴定PEX和PEX- g之间的基因表达差异；4)确定和招募更多的PEX患者和家庭。这些研究对于了解PEX的分子基础和任何可能导致青光眼发展的修饰性遗传因素至关重要。杜克大学眼科是培养医生科学家的理想场所，在培养有前途的临床科学家方面有着良好的记录。