CAREER: Mechanobiology of Mesenchymal-Epithelial Transition

职业:间充质-上皮转化的力学生物学

基本信息

  • 批准号:
    1751785
  • 负责人:
  • 金额:
    $ 50万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-05-01 至 2024-04-30
  • 项目状态:
    已结题

项目摘要

When cells are weakly attached to each other, they are able to migrate. This happens when cancer spreads, but also when an embryo grows. Whether cells can change from ones that move into ones that remain in the same place is partly dependent on the tissue stiffness. If we better understand this change in cells, it will improve our understanding of how cancer progresses and how our organs grow. The change from mobile to a static cells is call mesenchymal-epithelial transition (MET). MET is important to kidney and heart development, wound healing and cancer metastasis. When MET happens, migrating cells change so that they are immobile and tightly bound to neighboring cells. MET depends on tissue stiffness, but the details of the dependence aren't known. This Faculty Early Career Development Program (CAREER) project will measure the response of cells to dynamic changes in matrix stiffness and determine how EMT is affected by tissue stiffness. This will help in understanding how embryos grow, how to better manufacture artificial tissues and in building 'organs on a chip' that can be used for drug discovery research. The PI and graduate student supported through this project will develop and implement a workshop for grade 6-12 teachers focused on biomechanics and mechanobiology concepts so that they can better teach their students, including how engineering research impacts society. Mesenchymal-epithelial transition (MET) is a phenotypic change in which migratory cells with weak cell-cell contacts transition to tightly bound cells exhibiting apical-basal polarity. MET is central to embryonic remodeling, establishment of organ architecture, wound healing, reprogramming of somatic cells into induced pluripotent stem cells, and metastatic dissemination of cancer cells. While it is recognized that mechanical properties of the cellular niche change dynamically during MET-associated processes in vivo, important questions still remain regarding how microenvironmental physical properties regulate MET. The goal of this CAREER project is to develop a dynamic hydrogel system that recapitulates changes in tissue mechanical properties during MET-associated events, and then to use this system to determine the expression of genes associated with epithelial and mesenchymal phenotypes, cytoskeletal remodeling, and cell migration. Further studies will elucidate the role of key mechanoresponsive signaling molecules and epigenetic remodeling in regulating MET response to mechanical signals. The establishment of molecular mechanisms linking tissue mechanics and MET will result in a better understanding of mechanotransduction processes and will provide insight into how mechanical signals regulate cell plasticity. The research program provides the foundation for educational and outreach efforts aimed toward incorporating positive themes about the impact of engineering and mechanobiology on society into engineering curricula and into recruitment efforts directed toward grade 6-12 through graduate-level students. A workshop for grade 6-12 teachers focused on biomechanics and mechanobiology concepts will be developed and implemented and will demonstrate how research impacts society.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
当细胞彼此弱附着时,它们能够迁移。 这种情况发生在癌症扩散时,也发生在胚胎生长时。 细胞是否能从移动的细胞变成留在原地的细胞,部分取决于组织的硬度。如果我们更好地了解细胞的这种变化,它将提高我们对癌症如何发展以及我们的器官如何生长的理解。间充质-上皮细胞转变(MET)是细胞从移动的到静止的转变。MET对肾脏和心脏发育、伤口愈合和癌症转移都很重要。当MET发生时,迁移细胞发生变化,使它们不动并与相邻细胞紧密结合。MET依赖于组织硬度,但这种依赖性的细节尚不清楚。这个教师早期职业发展计划(CAREER)项目将测量细胞对基质硬度动态变化的反应,并确定EMT如何受到组织硬度的影响。这将有助于了解胚胎如何生长,如何更好地制造人工组织,以及在芯片上构建可用于药物发现研究的“器官”。PI和研究生通过这个项目支持将开发和实施6-12年级的教师专注于生物力学和机械生物学概念,使他们可以更好地教他们的学生,包括工程研究如何影响社会研讨会。 间质-上皮转化(MET)是一种表型变化,其中具有弱细胞-细胞接触的迁移细胞转化为表现出顶部-基底极性的紧密结合的细胞。MET是胚胎重塑、器官结构建立、伤口愈合、体细胞重编程为诱导多能干细胞和癌细胞转移性传播的核心。虽然人们认识到,在体内MET相关过程中,细胞生态位的机械特性动态变化,但关于微环境物理特性如何调节MET的重要问题仍然存在。该CAREER项目的目标是开发一种动态水凝胶系统,该系统可重现MET相关事件期间组织力学特性的变化,然后使用该系统确定与上皮和间充质表型、细胞骨架重塑和细胞迁移相关的基因表达。进一步的研究将阐明关键的机械应答信号分子和表观遗传重构在调节MET对机械信号的应答中的作用。建立连接组织力学和MET的分子机制将导致更好地理解机械转导过程,并将提供深入了解机械信号如何调节细胞可塑性。该研究计划为教育和推广工作提供了基础,旨在将工程和机械生物学对社会的影响的积极主题纳入工程课程,并通过研究生水平的学生直接面向6-12年级的招聘工作。一个针对6-12年级教师的生物力学和机械生物学概念的研讨会将被开发和实施,并将展示研究如何影响社会。该奖项反映了NSF的法定使命,并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
User-friendly chemical patterning with digital light projection polymer brush photolithography
  • DOI:
    10.1016/j.eurpolymj.2021.110652
  • 发表时间:
    2021-07
  • 期刊:
  • 影响因子:
    6
  • 作者:
    Michele Fromel;Raymond L. Crisci;Chinmay S. Sankhe;D. R. Hickey;T. Tighe;Esther W. Gomez;Christian W. Pester
  • 通讯作者:
    Michele Fromel;Raymond L. Crisci;Chinmay S. Sankhe;D. R. Hickey;T. Tighe;Esther W. Gomez;Christian W. Pester
Crosstalk between ERK and MRTF‐A signaling regulates TGFβ1‐induced epithelial‐mesenchymal transition
ERK 和 MRTF 之间的串扰 —A 信号传导调节 TGFβ1 — 诱导的上皮 — 间质转化
  • DOI:
    10.1002/jcp.30705
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    5.6
  • 作者:
    Nalluri, Sandeep M.;Sankhe, Chinmay S.;O'Connor, Joseph W.;Blanchard, Paul L.;Khouri, Joelle N.;Phan, Steven H.;Virgi, Gage;Gomez, Esther W.
  • 通讯作者:
    Gomez, Esther W.
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Esther Gomez其他文献

Community and shotgun metagenomic analysis of <em>Alligator mississippiensis</em> oral cavity and GI tracts reveal complex ecosystems and potential reservoirs of antibiotic resistance
  • DOI:
    10.1016/j.cbpa.2022.111319
  • 发表时间:
    2022-12-01
  • 期刊:
  • 影响因子:
  • 作者:
    Julissa Perez-Marron;Ciara Sanders;Esther Gomez;Sean Escopete;Tomasz Owerkowicz;Paul M. Orwin
  • 通讯作者:
    Paul M. Orwin

Esther Gomez的其他文献

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{{ truncateString('Esther Gomez', 18)}}的其他基金

REU Site: Integration of Biology and Materials in Chemical Engineering
REU 网站:化学工程中生物学和材料的整合
  • 批准号:
    1950639
  • 财政年份:
    2020
  • 资助金额:
    $ 50万
  • 项目类别:
    Standard Grant
REU Site: Integration of Biology and Materials in Chemical Engineering
REU 网站:化学工程中生物学和材料的整合
  • 批准号:
    1659497
  • 财政年份:
    2017
  • 资助金额:
    $ 50万
  • 项目类别:
    Standard Grant

相似海外基金

Mechanobiology of Endothelial-to-Mesenchymal Transition in Cardiovascular Calcification
心血管钙化中内皮向间质转化的力学生物学
  • 批准号:
    10631013
  • 财政年份:
    2022
  • 资助金额:
    $ 50万
  • 项目类别:
Mechanobiology of Endothelial-to-Mesenchymal Transition in Cardiovascular Calcification
心血管钙化中内皮向间质转化的力学生物学
  • 批准号:
    10442385
  • 财政年份:
    2020
  • 资助金额:
    $ 50万
  • 项目类别:
Mechanobiology of Endothelial-to-Mesenchymal Transition in Cardiovascular Calcification
心血管钙化中内皮向间质转化的力学生物学
  • 批准号:
    10625842
  • 财政年份:
    2020
  • 资助金额:
    $ 50万
  • 项目类别:
Mechanobiology of Endothelial-to-Mesenchymal Transition in Cardiovascular Calcification
心血管钙化中内皮-间质转化的力学生物学
  • 批准号:
    10187651
  • 财政年份:
    2020
  • 资助金额:
    $ 50万
  • 项目类别:
Microengineered Extracellular Environment for Mesenchymal Stem Cell Mechanobiology
间充质干细胞力学生物学的微工程细胞外环境
  • 批准号:
    471047-2015
  • 财政年份:
    2016
  • 资助金额:
    $ 50万
  • 项目类别:
    Postdoctoral Fellowships
Exploiting mesenchymal stem cell mechanobiology to enhance the success of burn wound cell therapy.
利用间充质干细胞力学生物学来提高烧伤创面细胞治疗的成功率。
  • 批准号:
    362321
  • 财政年份:
    2016
  • 资助金额:
    $ 50万
  • 项目类别:
    Fellowship Programs
Microengineered Extracellular Environment for Mesenchymal Stem Cell Mechanobiology
间充质干细胞力学生物学的微工程细胞外环境
  • 批准号:
    471047-2015
  • 财政年份:
    2015
  • 资助金额:
    $ 50万
  • 项目类别:
    Postdoctoral Fellowships
CAREER: Directing Epithelial-Mesenchymal Tissue Self-Structuring and Remodeling With Multi-scale Mechanical Interactions and Principles of Mechanobiology
职业:利用多尺度机械相互作用和机械生物学原理指导上皮间充质组织的自我构造和重塑
  • 批准号:
    1452728
  • 财政年份:
    2015
  • 资助金额:
    $ 50万
  • 项目类别:
    Standard Grant
Endothelial to Mesenchymal Transformation Mechanobiology
内皮细胞向间充质细胞转化的力学生物学
  • 批准号:
    1436173
  • 财政年份:
    2014
  • 资助金额:
    $ 50万
  • 项目类别:
    Standard Grant
Microengineered Extracellular Environment for Mesenchymal Stem Cell Mechanobiology
间充质干细胞力学生物学的微工程细胞外环境
  • 批准号:
    471047-2015
  • 财政年份:
    2014
  • 资助金额:
    $ 50万
  • 项目类别:
    Postdoctoral Fellowships
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