Molecular Mechanisms in Sweat Gland Development

汗腺发育的分子机制

基本信息

  • 批准号:
    9185264
  • 负责人:
  • 金额:
    $ 12.4万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-01-21 至 2018-04-30
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): I have been devoted and aiming to establish an independent and innovative research program in epithelial stem cell biology and to study skin-related diseases. The K01 mentored research scientist development award will present great opportunities for me to acquire additional skills and expertise that are essential for my transitio into an independent position. As a postdoctoral fellow in the laboratory of Dr. Elaine Fuchs at The Rockefeller University, I find myself in a premium scientific environment that fully supports my career development and provides all the equipments, resources, facilities, and trainings that are necessary for me to complete this proposed work successfully and to transition into an independent faculty position. Eccrine sweat glands are widely distributed in most areas of human skin, and its proper maintenance and functioning is crucial for optimal thermoregulation and water balance throughout our lifetime. Patients born with Hypohidrotic (Anhydrotic) Ectodermal Dysplasia (HED) have defects in sweat gland development and suffer from constant high fever due to inability to dissipate heat efficiently, and their lives are at risk. The long-tem objective of this proposed research is to understand the molecular mechanisms in sweat gland development, more specifically, the epithelial-mesenchymal signaling crosstalk that are involved. Knowledge acquired from this proposed research will contribute to future sweat gland regeneration that may benefit patients with sweat gland deficiency. Previous studies on Human HED patients revealed that mutations in WNT10a, in addition to components in EDA pathways, cause defective sweat gland development. As EDA pathway has been well characterized to be indispensable for initiation of various ectodermal appendages, the role of Wnt signaling in the context of sweat gland development is unknown. In addition, epithelial-mesenchymal signaling crosstalk has been shown to dictate epithelial cell fate, but exact signaling components that are involved remain elusive. Based on prior knowledge, I hypothesize that Wnt signaling triggers changes in the expression of secreting factors from mesenchyme, which then in turn determine the cell fate of epithelial progenitors to derive sweat glands. Specifically in this research proposal, I plan to: 1) Characterize the temporal and spatial activities of Wnt signaling during sweat gland initiation and morphogenesis; 2) Identify mesenchymal signals that specify sweat gland cell fate and support glandular differentiation; 3) Determine whether BMP-Shh antagonism occurs in the context of sweat gland development. With the support of a K01 award, I will obtain the necessary training and techniques essential for my transition into an independent research position, and expand my expertise and capability to perform research of high quality. I will also develop additional skills on networking, management, and mentoring, which together will equip me to achieve my future research goals as an independent investigator.
 工作描述(由申请人提供):我一直致力于建立一个独立的、创新的上皮干细胞生物学研究项目,并研究皮肤相关疾病。K 01指导研究科学家发展奖将为我提供很好的机会,让我获得额外的技能和专业知识,这对我过渡到独立的职位至关重要。作为洛克菲勒大学伊莱恩·富克斯博士实验室的博士后研究员,我发现自己处于一个优质的科学环境中,完全支持我的职业发展,并提供所有必要的设备,资源,设施和培训,使我成功完成这项拟议的工作,并过渡到一个独立的教师职位。 外泌汗腺广泛分布在人体皮肤的大部分区域,其适当的维护和功能对于我们一生中的最佳体温调节和水分平衡至关重要。患有先天性少汗(无汗)外胚层发育不良(HED)的患者,汗腺发育有缺陷,因无法有效散热而持续高烧,生命危在旦夕。这项研究的长期目标是了解汗腺发育的分子机制,更具体地说,涉及上皮-间充质信号串扰。从这项拟议的研究中获得的知识将有助于未来的汗腺再生,可能使汗腺缺乏症患者受益。 先前对人类HED患者的研究表明,除了EDA途径中的组分外,WNT 10a的突变会导致汗腺发育缺陷。由于EDA途径已被充分表征为对于各种外胚层附属物的起始是必不可少的,因此Wnt信号传导在汗腺发育背景中的作用是未知的。此外,上皮-间充质信号串扰已被证明决定上皮细胞的命运,但涉及的确切信号组分仍然难以捉摸。基于先前的知识,我假设,Wnt信号触发的变化,从间充质分泌因子的表达,然后反过来决定上皮祖细胞的细胞命运,以获得汗腺。具体来说,在这项研究提案中,我计划:1)表征汗腺启动和形态发生过程中Wnt信号的时空活动; 2)确定指定汗腺细胞命运和支持腺体分化的间充质信号; 3)确定BMP-Shh拮抗作用是否发生在汗腺发育的背景下。 在K 01奖的支持下,我将获得必要的培训和技术,这对我过渡到独立研究职位至关重要,并扩大我的专业知识和能力,以进行高质量的研究。我还将开发网络,管理和指导,这将使我能够实现我作为一个独立的研究者未来的研究目标的额外技能。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Catherine Pei-Ju Lu其他文献

Catherine Pei-Ju Lu的其他文献

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{{ truncateString('Catherine Pei-Ju Lu', 18)}}的其他基金

Molecular Mechanisms in Sweat Gland Development
汗腺发育的分子机制
  • 批准号:
    10660583
  • 财政年份:
    2023
  • 资助金额:
    $ 12.4万
  • 项目类别:
Molecular mechanism of neuronal control in sweat gland development
神经元控制汗腺发育的分子机制
  • 批准号:
    10928886
  • 财政年份:
    2023
  • 资助金额:
    $ 12.4万
  • 项目类别:
Molecular Mechanisms in Sweat Gland Development
汗腺发育的分子机制
  • 批准号:
    8822013
  • 财政年份:
    2015
  • 资助金额:
    $ 12.4万
  • 项目类别:
Molecular Mechanisms in Sweat Gland Development
汗腺发育的分子机制
  • 批准号:
    8996554
  • 财政年份:
    2015
  • 资助金额:
    $ 12.4万
  • 项目类别:
Epithelial Stem Cell Migration during Wound Repair
伤口修复过程中上皮干细胞的迁移
  • 批准号:
    8260459
  • 财政年份:
    2011
  • 资助金额:
    $ 12.4万
  • 项目类别:
Epithelial Stem Cell Migration during Wound Repair
伤口修复过程中上皮干细胞的迁移
  • 批准号:
    8061143
  • 财政年份:
    2011
  • 资助金额:
    $ 12.4万
  • 项目类别:
Epithelial Stem Cell Migration during Wound Repair
伤口修复过程中上皮干细胞的迁移
  • 批准号:
    8434080
  • 财政年份:
    2011
  • 资助金额:
    $ 12.4万
  • 项目类别:
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