EPH-RECEPTOR SIGNALING IN LENS DEVELOPMENT AND AGING

项目摘要 Eph受体酪氨酸激酶激活复杂的信号网络，参与不同的生物和 病理过程包括胚胎发育、组织再生、免疫监测、肿瘤 进展和病毒感染。最近，编码其中一种受体EphA2的基因发生了变异 与遗传性和年龄相关的人类白内障有关，而EphA2已被发现是一种 晶状体膜蛋白质组有丰富的成分，但知之甚少。这个项目的总体目标是 研究是为了促进对EPH受体信号在晶状体发育和老化中的理解。在这 建议我们将采用跨学科的方法来阐明连接基因的分子机制 EphA2随晶状体表型的变化。首先，我们将执行定向测序以确定 EphA2编码变异与晶状体老化的关系第二，我们将使用基因靶向的小鼠和 用于表征EphA2在晶状体发育过程中的功能和功能障碍的成像技术。最后我们会 采用蛋白质组学技术来表征EphA2信号和在晶状体中的处理。结果来自 这些研究将为EPH受体信号在晶状体发育和发育中的作用提供新的见解 衰老，在白内障形成的背景下--视力受损的一个重要原因。

Project Summary EPH-receptor tyrosine kinases activate complex signaling networks involved in diverse biological and pathological processes including embryonic development, tissue regeneration, immune surveillance, tumor progression and viral infection. Recently, variations in the gene encoding one of these receptors, EPHA2, have been associated with inherited and age-related forms of human cataract, and EPHA2 has been identified as an abundant, but poorly understood, component of the lens membrane proteome. The overall goal of this research is to advance understanding of EPH-receptor signaling in lens development and aging. In this proposal we will conduct an interdisciplinary approach to elucidate molecular mechanisms that connect genetic variation in EPHA2 with lens phenotype. First, we will perform targeted-sequencing to determine the relationship between EPHA2 coding variation and lens aging. Second, we will use gene-targeted mice and imaging techniques to characterize EPHA2 function and dysfunction during lens development. Finally we will undertake proteomics techniques to characterize EPHA2 signaling and processing in the lens. Results from these studies will provide new insights regarding the role of EPH-receptor signaling in lens development and aging, within the context of cataract formation - an important cause of visual impairment.