Notch Signaling in the Corneal Epithelium

角膜上皮中的Notch信号传导

• 批准号: 7494024
• 负责人: ALI R DJALILIAN
• 金额: $ 23.66万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7494024
• 关键词: Affect; Aniridia; Biology; Blindness; Cells; Chemical Injury; Cicatrix; Clinical; Condition; Cornea; Corneal Injury; Defect; Development; Development Plans; Differentiation and Growth; Disease; Epithelial; Epithelial Cells; Epithelium; Eye; Genetic; Goals; Growth; Hand; Human; Lead; Ligands; Mentors; Modeling; Mus; Natural regeneration; Pain; Pathologic; Pathway interactions; Patients; Physiological; Positioning Attribute; Recurrence; Regulation; Regulatory Pathway; Research; Research Personnel; Resources; Role; Scientist; Signal Transduction; Stem cells; Structure; Supervision; Surface; Testing; Training; Translating; United States National Institutes of Health; Visual; Work; Wound Healing; career; corneal epithelial stem cells; corneal epithelium; design; experience; improved; in vivo; innovation; limbal; notch protein; novel; ocular surface; prevent; programs; receptor

DESCRIPTION (provided by applicant): The corneal epithelium is one of the most sensitive and critical structures of the eye. Currently, the pathways that regulate the differentiation and renewal of the corneal epithelial cells are largely unknown. Understanding the precise regulatory pathways governing corneal epithelial regeneration is critical for the development of effective treatments for many corneal wound healing disorders. Notch signaling, which is an important pathway in cell-fate determination, has recently been implicated in corneal epithelial growth and differentiation. The long-term objective of this application is two fold. First, is to contribute to the development of novel and innovative treatments for patients with ocular surface disease by defining the role of Notch signaling in the regulation of corneal epithelial growth and differentiation. Second, is to further develop the career of the applicant as a clinician-scientist and facilitate his transition to becoming an independent investigator. To accomplish the research objectives of this application, the following three specific aims will be pursued: (1) Determine the expression of Notch receptors and ligands in the corneal epithelial cells during proliferation and differentiation. (2) Characterize the effects of induced Notch activation and inhibition on the growth and differentiation of the human corneal epithelial cells. (3) Determine the in vivo effects of Notch activation and inhibition in the murine corneal epithelium. In addition to pursuing these specific aims, the applicant will follow a carefully designed career development plan involving didactic and hands-on training under the direct supervision of experienced mentors. Overall, these studies will improve our understanding of how the surface of the eye is regenerated. These results will lead to the development of new treatments for patients with disabling visual conditions involving the surface of the eye.

描述（由申请人提供）：角膜上皮是眼睛最敏感和最关键的结构之一。目前，调节角膜上皮细胞分化和更新的途径很大程度上未知。 了解控制角膜上皮再生的精确调控途径对于开发许多角膜伤口愈合障碍的有效治疗方法至关重要。 Notch信号传导是细胞命运决定的重要途径，最近与角膜上皮生长和分化有关。该应用程序的长期目标有两个。首先，通过明确Notch信号在角膜上皮生长和分化调节中的作用，为眼表疾病患者开发新颖和创新的治疗方法做出贡献。其次，是进一步发展申请人作为临床医生科学家的职业生涯，并促进他向独立研究者的过渡。为了完成本申请的研究目标，将追求以下三个具体目标：（1）确定角膜上皮细胞在增殖和分化过程中Notch受体和配体的表达。 (2)表征诱导Notch激活和抑制对人角膜上皮细胞生长和分化的影响。 (3) 确定Notch激活和抑制对小鼠角膜上皮的体内影响。除了追求这些具体目标外，申请人还将遵循精心设计的职业发展计划，包括在经验丰富的导师的直接监督下进行教学和实践培训。总的来说，这些研究将提高我们对眼睛表面如何再生的理解。这些结果将导致针对涉及眼睛表面的视力障碍患者开发新的治疗方法。