The Roles of Autophagy in Limbal/Corneal Epithelia.

自噬在角膜缘/角膜上皮中的作用。

基本信息

  • 批准号:
    10400950
  • 负责人:
  • 金额:
    $ 48.08万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-05-01 至 2024-02-29
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT The anterior surface of the eye functions as a barrier to the external environment, protects the delicate underlying structures from injury, supports a tear film and maintains transparency. These functions are achieved, in part, through the corneal and limbal epithelia, which must maintain proper proliferation and differentiation. Autophagy, a catabolic process by which cells adapt to intrinsic and extrinsic stress-related situations, has been shown to also regulate proliferation and differentiation. Despite the many advances made in our understanding of corneal and limbal epithelial biology, autophagy remains largely unstudied. We have recently reported that: (i) under resting conditions, autophagy is greater in limbal epithelial basal compared with corneal epithelial basal cells; (ii) autophagy contributes to limbal epithelial proliferative capacity; and (iii) autophagy enables proper activation of transit amplifying (TA) cells following wounding. We also have preliminary evidence that: (i) NUS1 is a novel upstream regulator of autophagy in the limbal epithelium; (ii) blocking autophagy impairs corneal epithelial differentiation and the removal of nuclear material (nucelophagy); and (iii) the receptor tyrosine kinase, EphA2, positively affects corneal epithelial differentiation via regulating end stage autophagy. These observations lead us to hypothesize that autophagy is required to maintain limbal epithelial stem and TA cell homeostasis as well as insure proper corneal epithelial differentiation. We propose to test this hypothesis by focusing on how autophagy: (i) affects limbal epithelial stem cell proliferation; (ii) regulates differentiation in the corneal epithelium; and (iii) is regulated by EphA2 in the corneal epithelium. To accomplish these goals, we will capitalize on our ability to conduct gain- and loss-of-function studies of autophagy-related genes and their key up-stream regulators in complimentary model systems that include cultured human limbal (HLEKs) and corneal (HCEKs) epithelial cells, 3-D raft cultures of limbal and corneal epithelia, and mouse models of impaired autophagy and EphA2 signaling. We will assess the functional consequences of such modulations with a combination of morphogenetic (including Structured Illumination Microscopy and TEM), biochemical, molecular biological, cell biological and physiological approaches. By focusing on autophagy, our proposal represents a new approach to study the regulation of: (i) limbal stem and TA cell proliferation; and (ii) corneal epithelial differentiation and nucelophagy. Such knowledge has clinical applicability as sustaining proliferation is necessary for the proper expansion of cultured HLEKs used in ex vivo transplantation as well as in wound healing. The impact of autophagy and nucleophagy on corneal epithelial differentiation has translational relevance since aberrant differentiation is a feature of diseases of the corneal epithelium (e.g., aniridia, chemical burns) and modulation of autophagy-associated genes are potential treatment modalities, Understanding how autophagy is regulated in corneal epithelium is essential as this tissue is routinely subjected to stress, which requires a proper autophagic response to maintain homeostasis.
项目总结/文摘

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

ROBERT M LAVKER其他文献

ROBERT M LAVKER的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('ROBERT M LAVKER', 18)}}的其他基金

Reversing the ocular impact of NM and SM through novel therapies
通过新疗法扭转 NM 和 SM 对眼部的影响
  • 批准号:
    10282412
  • 财政年份:
    2021
  • 资助金额:
    $ 48.08万
  • 项目类别:
Reversing the ocular impact of NM and SM through novel therapies
通过新疗法扭转 NM 和 SM 对眼部的影响
  • 批准号:
    10682631
  • 财政年份:
    2021
  • 资助金额:
    $ 48.08万
  • 项目类别:
Barrier Damage and The Immune CascadeNorthwestern University CounterACT Center of Excellence (NUCCX)
屏障损伤和免疫级联西北大学 CounterACT 卓越中心 (NUCCX)
  • 批准号:
    10282406
  • 财政年份:
    2021
  • 资助金额:
    $ 48.08万
  • 项目类别:
Reversing the ocular impact of NM and SM through novel therapies
通过新疗法扭转 NM 和 SM 对眼部的影响
  • 批准号:
    10490420
  • 财政年份:
    2021
  • 资助金额:
    $ 48.08万
  • 项目类别:
Barrier Damage and The Immune CascadeNorthwestern University CounterACT Center of Excellence (NUCCX)
屏障损伤和免疫级联西北大学 CounterACT 卓越中心 (NUCCX)
  • 批准号:
    10682598
  • 财政年份:
    2021
  • 资助金额:
    $ 48.08万
  • 项目类别:
Barrier Damage and The Immune CascadeNorthwestern University CounterACT Center of Excellence (NUCCX)
屏障损伤和免疫级联西北大学 CounterACT 卓越中心 (NUCCX)
  • 批准号:
    10490379
  • 财政年份:
    2021
  • 资助金额:
    $ 48.08万
  • 项目类别:
The Roles of Autophagy in Limbal/Corneal Epithelia.
自噬在角膜缘/角膜上皮中的作用。
  • 批准号:
    10225304
  • 财政年份:
    2018
  • 资助金额:
    $ 48.08万
  • 项目类别:
The Roles of Autophagy in Limbal/Corneal Epithelia.
自噬在角膜缘/角膜上皮中的作用。
  • 批准号:
    9910410
  • 财政年份:
    2018
  • 资助金额:
    $ 48.08万
  • 项目类别:
2016 Cornea, Biology and Pathobiology Gordon Research Conference & Gordon Research Seminar
2016年角膜、生物学和病理学戈登研究会议
  • 批准号:
    9052308
  • 财政年份:
    2015
  • 资助金额:
    $ 48.08万
  • 项目类别:
Post Graduate Program in Cutaneous Biology
皮肤生物学研究生课程
  • 批准号:
    8844209
  • 财政年份:
    2012
  • 资助金额:
    $ 48.08万
  • 项目类别:

相似海外基金

Hormone therapy, age of menopause, previous parity, and APOE genotype affect cognition in aging humans.
激素治疗、绝经年龄、既往产次和 APOE 基因型会影响老年人的认知。
  • 批准号:
    495182
  • 财政年份:
    2023
  • 资助金额:
    $ 48.08万
  • 项目类别:
Parkinson's disease and aging affect neural activation during continuous gait alterations to the split-belt treadmill: An [18F] FDG PET Study.
帕金森病和衰老会影响分体带跑步机连续步态改变期间的神经激活:[18F] FDG PET 研究。
  • 批准号:
    400097
  • 财政年份:
    2019
  • 资助金额:
    $ 48.08万
  • 项目类别:
The elucidation of the mechanism by which intestinal epithelial cells affect impaired glucose tolerance during aging
阐明衰老过程中肠上皮细胞影响糖耐量受损的机制
  • 批准号:
    19K09017
  • 财政年份:
    2019
  • 资助金额:
    $ 48.08万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Does aging of osteocytes adversely affect bone metabolism?
骨细胞老化会对骨代谢产生不利影响吗?
  • 批准号:
    18K09531
  • 财政年份:
    2018
  • 资助金额:
    $ 48.08万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Links between affect, executive function, and prefrontal structure in aging: A longitudinal analysis
衰老过程中情感、执行功能和前额叶结构之间的联系:纵向分析
  • 批准号:
    9766994
  • 财政年份:
    2018
  • 资助金额:
    $ 48.08万
  • 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
  • 批准号:
    10166936
  • 财政年份:
    2017
  • 资助金额:
    $ 48.08万
  • 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
  • 批准号:
    9320090
  • 财政年份:
    2017
  • 资助金额:
    $ 48.08万
  • 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
  • 批准号:
    9761593
  • 财政年份:
    2017
  • 资助金额:
    $ 48.08万
  • 项目类别:
Experimental Model of Depression in Aging: Insomnia, Inflammation, and Affect Mechanisms
衰老过程中抑郁症的实验模型:失眠、炎症和影响机制
  • 批准号:
    9925164
  • 财政年份:
    2016
  • 资助金额:
    $ 48.08万
  • 项目类别:
Experimental Model of Depression in Aging: Insomnia, Inflammation, and Affect Mechanisms
衰老过程中抑郁症的实验模型:失眠、炎症和影响机制
  • 批准号:
    9345997
  • 财政年份:
    2016
  • 资助金额:
    $ 48.08万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了