In Vivo Multiphoton Based Imaging of Complex Cancer Cell Behavior

基于体内多光子的复杂癌细胞行为成像

基本信息

项目摘要

PROJECT ABSTRACT Recent results have led many to propose a microenvironment-dependent model for initiation of migratory and disseminating tumor cell behavior at both the primary tumor and within target organs that is not stably specified by genetic mutation and that is transient in time and space. This view is called the microenvironment model of metastasis. The testing of this model has been hampered in part by the lack of high-resolution in vivo microscopy methods and genetically-encoded fluorescent probes for tumor deep-tissue imaging that allow definitive identification of the microenvironments involved in initiating the migratory and disseminating tumor cell phenotype. Equally problematic are the limitations of standard analyses of expression profiles. Standard analysis of expression profiles in cancer involves identifying consistently up- and down- regulated genes. While these techniques are likely to identify sets of genes directly within affected networks, our previous theoretical results have shown that major perturbations (of which cancer is one) cause expression changes far beyond the pathway involved. Crucially, these more distant changes will be highly variable depending on the genetic background, thus tumor expression profiles are expected to be greatly dissimilar between individuals. Using this hypothesis we propose a novel systems-level analysis of cancer (SLAC), which identifies key genes based upon increase in expression variability, and which in turn offers the possibility of discovering highly non-intuitive pathway interactions connected with microenvironment regulation of breast cancer progression. By combining the multiphoton high-resolution microscopy having the wide range of excitation wavelengths with the proposed multicolor far-red fluorescent probes as versatile as conventional GFP we will advance deep-tissue cell labeling and imaging of tumor cells dynamics in vivo. This approach will make possible the intravital imaging of simultaneously up to six genetically-encoded colors in tumor studies. This in turn will provide a way to discriminate and subsequently isolate the tumor cells of multiple metastatic phenotypes based on the fluorescent color-encoded expression patterns. By correlating the behavior and fate of migrating and disseminating tumor cells obtained by the multiphoton imaging at a single-cell level with SLAC analysis of expression profiles of these cells, we will identify the key genes driving tumor cell behaviors involved in metastasis such as cell migration and dissemination.
项目摘要

项目成果

期刊论文数量(0)
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Vladislav Verkhusha其他文献

Vladislav Verkhusha的其他文献

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{{ truncateString('Vladislav Verkhusha', 18)}}的其他基金

Head-mounted Photoacoustic Imaging of Deep-brain Neural Activities in Freely Behaving Animals
自由行为动物深脑神经活动的头戴式光声成像
  • 批准号:
    9924909
  • 财政年份:
    2020
  • 资助金额:
    $ 76.6万
  • 项目类别:
Near-infrared fluorescent probes and optogenetic tools
近红外荧光探针和光遗传学工具
  • 批准号:
    10551976
  • 财政年份:
    2017
  • 资助金额:
    $ 76.6万
  • 项目类别:
Calcium biosensors for deep-tissue imaging and spectral multiplexing
用于深层组织成像和光谱复用的钙生物传感器
  • 批准号:
    9526574
  • 财政年份:
    2017
  • 资助金额:
    $ 76.6万
  • 项目类别:
Near-Infrared Fluorescent Proteins, Biosensors and Optogenetic Tools
近红外荧光蛋白、生物传感器和光遗传学工具
  • 批准号:
    10163867
  • 财政年份:
    2017
  • 资助金额:
    $ 76.6万
  • 项目类别:
Super Resolution PALM/STORM Microscopy System In Multi-User Facility
多用户设施中的超分辨率 PALM/STORM 显微镜系统
  • 批准号:
    8640512
  • 财政年份:
    2014
  • 资助金额:
    $ 76.6万
  • 项目类别:
Engineering bacterial phytochromes for near-infrared imaging in mammals
用于哺乳动物近红外成像的细菌光敏色素工程
  • 批准号:
    9857688
  • 财政年份:
    2014
  • 资助金额:
    $ 76.6万
  • 项目类别:
Engineering bacterial phytochromes for near-infrared imaging in mammals
用于哺乳动物近红外成像的细菌光敏色素工程
  • 批准号:
    9220835
  • 财政年份:
    2014
  • 资助金额:
    $ 76.6万
  • 项目类别:
Engineering bacterial phytochromes for near-infrared imaging in mammals
用于哺乳动物近红外成像的细菌光敏色素工程
  • 批准号:
    9024584
  • 财政年份:
    2014
  • 资助金额:
    $ 76.6万
  • 项目类别:
In Vivo Multiphoton Based Imaging of Complex Cancer Cell Behavior
基于体内多光子的复杂癌细胞行为成像
  • 批准号:
    8231689
  • 财政年份:
    2011
  • 资助金额:
    $ 76.6万
  • 项目类别:
In Vivo Multiphoton Based Imaging of Complex Cancer Cell Behavior
基于体内多光子的复杂癌细胞行为成像
  • 批准号:
    8699512
  • 财政年份:
    2011
  • 资助金额:
    $ 76.6万
  • 项目类别:

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