Regulation of endothelial cell invasion, migration and cell junction plasticity

内皮细胞侵袭、迁移和细胞连接可塑性的调节

基本信息

  • 批准号:
    10685981
  • 负责人:
  • 金额:
    $ 39.98万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-09-01 至 2027-07-31
  • 项目状态:
    未结题

项目摘要

Project Summary One of the main research directions of my laboratory focuses on regulation of the endothelial barrier and endothelial cell migration. These processes are critical for physiological function of vascular system and they are often dysregulated in human diseases. A lot of progress has been made in understanding signaling that regulates endothelial barrier and cell migration. However, stimulation of endothelial cell migration during angiogenesis is a highly localized and transient event. Defining the role of the local and temporal components of angiogenic signaling has been challenging due to limitations of current tools. Furthermore, spatiotemporal regulation of the endothelial barrier by these stimuli has been poorly understood. Our proposed work will focus on determining how the location and duration of migratory signals direct endothelial cell invasion and migration through extracellular matrix, and how they affect the organization and permeability of the endothelial barrier. The endothelial barrier is controlled at the level of adherens junctions (AJs), cell-cell adhesion structures mediated by the transmembrane protein VE-cadherin. Phosphorylation-mediated signaling regulates the structure and permeability of AJs. In our recent studies, we described a dual role of tyrosine kinase Src and its phosphorylation of VE-cadherin in regulation of endothelial permeability. Our results demonstrated that Src- mediated phosphorylation induces formation of dynamic AJs that still retain their barrier function. This suggests a mechanism for the regulation of AJ plasticity that does not compromise barrier permeability during endothelial cell migration. In parallel studies, we dissected a mechanism of Src-regulated degradation of the extracellular matrix by the endothelial cell and discovered a novel cytoskeletal component that mediates formation of matrix-degrading podosomes. The studies proposed here will continue to build on our previous findings and focus on dissecting how phosphorylation of VE-cadherin and angiogenic signaling by Vascular Growth Factor Receptor 2 (VEGFR2), Sphingosine-1-phosphate Receptor 1 (S1PR1), and Src regulate plasticity of AJs as well as invasion and migration of endothelial cells. We will employ novel optogenetic tools that will allow us to interrogate these processes with precise spatial and temporal control. We will use engineered light-regulated VEGFR2, S1PR1, and Src to determine the effects of locally and temporally controlled angiogenic signals and dissect mechanisms that mediate regulation of AJs and migration of endothelial cells in three dimensional environment. Our long-term goal is to define the processes that control migration of endothelial cells and endothelial barrier function during angiogenesis.
项目总结

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)

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ANDREI V KARGINOV其他文献

ANDREI V KARGINOV的其他文献

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{{ truncateString('ANDREI V KARGINOV', 18)}}的其他基金

Optogenetic Control of Tumor Initiation and Tumor Progression in vivo
体内肿瘤发生和进展的光遗传学控制
  • 批准号:
    10640927
  • 财政年份:
    2022
  • 资助金额:
    $ 39.98万
  • 项目类别:
Regulation of endothelial cell invasion, migration and cell junction plasticity
内皮细胞侵袭、迁移和细胞连接可塑性的调节
  • 批准号:
    10406685
  • 财政年份:
    2022
  • 资助金额:
    $ 39.98万
  • 项目类别:
Optogenetic Control of Tumor Initiation and Tumor Progression in vivo
体内肿瘤发生和进展的光遗传学控制
  • 批准号:
    10413468
  • 财政年份:
    2022
  • 资助金额:
    $ 39.98万
  • 项目类别:
Synthetic Biology and Optogenetics Core
合成生物学和光遗传学核心
  • 批准号:
    10701925
  • 财政年份:
    2021
  • 资助金额:
    $ 39.98万
  • 项目类别:
Synthetic Biology and Optogenetics Core
合成生物学和光遗传学核心
  • 批准号:
    10170860
  • 财政年份:
    2021
  • 资助金额:
    $ 39.98万
  • 项目类别:
Synthetic Biology and Optogenetics Core
合成生物学和光遗传学核心
  • 批准号:
    10491052
  • 财政年份:
    2021
  • 资助金额:
    $ 39.98万
  • 项目类别:
Optogenetic tools for the dissection of oncogenic signaling mediated by kinases
用于解析激酶介导的致癌信号的光遗传学工具
  • 批准号:
    9891973
  • 财政年份:
    2018
  • 资助金额:
    $ 39.98万
  • 项目类别:
Src-mediated pathways regulating adherens junction assembly.
Src 介导的途径调节粘附连接组装。
  • 批准号:
    10166863
  • 财政年份:
    2017
  • 资助金额:
    $ 39.98万
  • 项目类别:
Src-mediated pathways regulating adherens junction assembly.
Src 介导的途径调节粘附连接组装。
  • 批准号:
    9310733
  • 财政年份:
    2017
  • 资助金额:
    $ 39.98万
  • 项目类别:
New methods for activation of kinases and kinase circuits in living cells.
激活活细胞中激酶和激酶电路的新方法。
  • 批准号:
    8243734
  • 财政年份:
    2012
  • 资助金额:
    $ 39.98万
  • 项目类别:

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Oral pathogen - mediated pro-tumorigenic transformation through disruption of an Adherens Junction - associated RNAi machinery
通过破坏粘附连接相关的 RNAi 机制,口腔病原体介导促肿瘤转化
  • 批准号:
    10752248
  • 财政年份:
    2024
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Adherens junction dynamics and function in epithelial tissue morphogenesis
粘附连接动力学和上皮组织形态发生中的功能
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    469118
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    2022
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Adherens Junction dysfunction in Hidradenitis Suppurativa
化脓性汗腺炎的粘附连接功能障碍
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    10701323
  • 财政年份:
    2022
  • 资助金额:
    $ 39.98万
  • 项目类别:
Adherens junction proteins in neuron-glia interactions
神经元-胶质细胞相互作用中的粘附连接蛋白
  • 批准号:
    9978138
  • 财政年份:
    2019
  • 资助金额:
    $ 39.98万
  • 项目类别:
Elucidation of the function of Focal adherens junction in morphogenesis
阐明焦点粘附连接在形态发生中的功能
  • 批准号:
    19K16145
  • 财政年份:
    2019
  • 资助金额:
    $ 39.98万
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    Grant-in-Aid for Early-Career Scientists
Identifying and characterizing the effect of Aip1 on adherens junction remodeling in Drosophila follicular epithelium
鉴定和表征 Aip1 对果蝇滤泡上皮粘附连接重塑的影响
  • 批准号:
    528450-2018
  • 财政年份:
    2018
  • 资助金额:
    $ 39.98万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Master's
Src-mediated pathways regulating adherens junction assembly.
Src 介导的途径调节粘附连接组装。
  • 批准号:
    10166863
  • 财政年份:
    2017
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    $ 39.98万
  • 项目类别:
Src-mediated pathways regulating adherens junction assembly.
Src 介导的途径调节粘附连接组装。
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The function and interaction of focal adhesion and adherens junction in bone mechanosensing and mechanotransduction.
粘着斑和粘附连接在骨力传感和力转导中的功能和相互作用。
  • 批准号:
    17K17307
  • 财政年份:
    2017
  • 资助金额:
    $ 39.98万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
a-catenin and its binding partners in adherens junction assembly and function
α-连环蛋白及其在粘附连接组装和功能中的结合伙伴
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    357714
  • 财政年份:
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    $ 39.98万
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