Core 1: Cellular diagnostics/imaging core
核心1:细胞诊断/成像核心
基本信息
- 批准号:10469358
- 负责人:
- 金额:$ 35.86万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-08-01 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAnimalsAtherosclerosisBlood CirculationBlood VesselsBlood flowBlood specimenBone MarrowCardiovascular DiseasesCellsCollaborationsColorCommunicationCustomData AnalysesDetectionDevelopmentDiagnostic ImagingEndotheliumExtracellular MatrixFluorescenceFunctional ImagingFutureGenesGenome engineeringHeartHematopoiesisHematopoieticHematopoietic stem cellsImageImaging technologyLaboratoriesLasersLesionLeukocyte TraffickingLeukocytesMeasurementMeasuresMethodsMicrodissectionMissionMolecularMolecular AnalysisMolecular ProfilingMusOpticsPeripheralPopulationProductionProteinsProtocols documentationResearch PersonnelResourcesScientific Advances and AccomplishmentsSignal TransductionTechniquesTechnologyTimeTissuesVascular Endothelial CellVascular PermeabilitiesWorkbasebone cellbone imagingcardiovascular effectscell typedesignhematopoietic stem cell nicheimage guidedimage processingimaging capabilitiesimaging modalityin vivoinnovationinstrumentationintravital microscopymeetingsmembermigrationmultiphoton imagingnon-invasive monitorreceptorsecond harmonicsingle cell analysistool
项目摘要
The mission of the cellular diagnostics/imaging core is two fold. First, we will provide state-of-the art imaging
technology and cell analysis tools to meet the scientific needs of the four projects in this PPG. We will work
closely with project investigators to perform quantitative measurements and data analysis, customizing
instrumentation and optimizing experimental protocols as necessary. Second, we will pursue new technical
innovations that will lead to future scientific advances beyond what can be accomplished with existing
technologies. The Core is a unique resource with deep expertise in optical technology, intravital microscopy,
instrumentation design and fabrication, as well as image processing and data analysis. We also have a
record of productive collaborations with multiple investigators in this PPG, including Dr. Scadden (Project 1),
Dr. Nahrendorf (Project 2), and Dr. Swirski (Project 3). Our laboratories are all physically co-located in the
same building, making the Core a common meeting place where team members from various laboratories
converge, not just to use the facility but also to interact and exchange ideas. To carry out the mission of the
Core, we propose the following Specific Aims. In Aim 1, we will work with Projects 1 and 4 to perform clonal
analysis of hematopoietic cells based on their expression of multi-color fluorescent proteins. We will expand
the multi-color capability of our in vivo flow cytometer, a technology developed in our laboratory for real-time
detection and quantification of fluorescent cells in the circulation of live animals without the need to draw
blood samples, to enable noninvasive monitoring of the clonal dynamics in the peripheral circulating
leukocyte population. In Aim 2, we will work with Project 2 to assess how the bone marrow (BM) vasculature
is altered by cardiovascular diseases (CVD). We will measure functional parameters such as blood flow,
vascular permeability, vascular reactivity, and trans-endothelial migration, by performing multiphoton
imaging of the BM vasculature together with second-harmonic imaging of the extracellular matrix
component. We will also work with Project 3 to characterize hematopoietic stem cell (HSC) localization and
dynamics in the BM in the settings of MI and atherosclerosis using gene-edited HSCs provided by the
Genome Engineering Core. In Aim 3 we propose to develop a new method to enable image-guided laser
microdissection and extraction of live cells from the BM for single cell molecular profiling. We will initially
focus on capturing BM vascular endothelial cells, as they form a critical component of the HSC niche and
also regulate leukocyte trafficking and macromolecular transport. The technique will bridge the existing
divide between single-cell analysis on the one hand, which provides molecular but no spatial information,
and live imaging on the other, which supplies the 3D spatial context lacking in the molecular analysis. The
technique can be extended in future studies to the analysis of other cell types and in other tissues.
细胞诊断/成像核心的任务是双重的。首先,我们将提供最先进的成像技术
技术和细胞分析工具,以满足这一PPG中四个项目的科学需求。我们会工作的
与项目调查人员密切合作,执行定量测量和数据分析,定制
必要时进行仪器和优化实验方案。第二,我们将追求新的技术
创新将导致未来的科学进步,而不是现有的
技术。核心是一种独特的资源,在光学技术、活体显微镜、
仪器设计和制造,以及图像处理和数据分析。我们还有一个
在此PPG中与多名研究人员进行富有成效的合作记录,包括斯卡登博士(项目1),
纳伦多夫博士(项目2)和斯维尔斯基博士(项目3)。我们的实验室都实际位于
同一建筑,使核心成为来自不同实验室的团队成员的公共会议场所
融合,不仅是为了使用设施,也是为了互动和交流思想。执行国家安全局的使命
核心是,我们提出了以下具体目标。在目标1中,我们将与项目1和4一起进行克隆
基于多色荧光蛋白表达的造血细胞分析。我们将扩大规模
我们的活体流式细胞仪的多色能力,这是我们实验室开发的一项实时技术
活体动物循环中荧光细胞的检测和量化
血液样本,以实现外周循环中克隆动态的非侵入性监测
白细胞数量。在目标2中,我们将与项目2合作,评估骨髓(BM)血管系统如何
是由心血管疾病(CVD)改变的。我们将测量功能参数,如血流量,
通过执行多光子,血管渗透性、血管反应性和跨内皮细胞迁移
骨髓血管成像与细胞外基质的二次谐波成像
组件。我们还将与项目3合作,以确定造血干细胞(HSC)的定位和
使用由提供的基因编辑的HSCs在心肌梗死和动脉粥样硬化环境中的骨髓动力学
基因组工程核心。在目标3中,我们建议开发一种新的方法来实现图像制导激光
从骨髓中显微解剖和提取活细胞,用于单细胞分子图谱。我们最初会
专注于捕获BM血管内皮细胞,因为它们构成了HSC利基和
也调节白细胞的运输和大分子的运输。这项技术将在现有的
一方面,单细胞分析提供了分子信息,但没有空间信息,
另一方面是实时成像,这提供了分子分析所缺乏的3D空间背景。这个
这项技术可以在未来的研究中扩展到其他细胞类型和其他组织的分析。
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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Charles P. Lin其他文献
Deep tissue single cell MSC ablation using a fiber laser source to evaluate therapeutic potential in osteogenesis imperfecta
使用光纤激光源进行深部组织单细胞 MSC 消融评估成骨不全症的治疗潜力
- DOI:
10.1117/12.2213292 - 发表时间:
2016 - 期刊:
- 影响因子:4.3
- 作者:
K. Tehrani;Emily G Pendleton;Charles P. Lin;L. Mortensen - 通讯作者:
L. Mortensen
Haematopoietic stem cells depend on Gαs-mediated signalling to engraft bone marrow
造血干细胞依赖于 Gαs 介导的信号传导来植入骨髓
- DOI:
10.1038/nature07859 - 发表时间:
2009-03-25 - 期刊:
- 影响因子:48.500
- 作者:
Gregor B. Adams;Ian R. Alley;Ung-il Chung;Karissa T. Chabner;Nathaniel T. Jeanson;Cristina Lo Celso;Emily S. Marsters;Min Chen;Lee S. Weinstein;Charles P. Lin;Henry M. Kronenberg;David T. Scadden - 通讯作者:
David T. Scadden
A Sensorless Adaptive Optics Scanning Laser Ophthalmoscope for Mice
用于小鼠的无传感器自适应光学扫描激光检眼镜
- DOI:
- 发表时间:
2006 - 期刊:
- 影响因子:0
- 作者:
D. Biss;R. Webb;Yaopeng Zhou;T. Bifano;Charles P. Lin - 通讯作者:
Charles P. Lin
Computational modeling of stress transient and bubble evolution in short-pulse laser-irradiated melanosome particles
短脉冲激光照射黑素体颗粒中应力瞬态和气泡演化的计算模型
- DOI:
- 发表时间:
1997 - 期刊:
- 影响因子:0
- 作者:
M. Strauss;P. Amendt;R. London;D. Maitland;M. Glinsky;Charles P. Lin;Michael W. Kelly - 通讯作者:
Michael W. Kelly
Declined presentation inflammatory modulation of hematopoietic stromal niche cells by TNF-α leads to rapid mobilization of hematopoietic stem/progenitor cells (HSPC) and neutrophils
- DOI:
10.1016/j.exphem.2015.06.134 - 发表时间:
2015-09-01 - 期刊:
- 影响因子:
- 作者:
Shin-Young Park;Eun Young Anna Han;Yookyung Jung;Charles P. Lin;Leslie E. Silberstein - 通讯作者:
Leslie E. Silberstein
Charles P. Lin的其他文献
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{{ truncateString('Charles P. Lin', 18)}}的其他基金
Local Skull Marrow Sensing and Response to CNS Inflammation
局部颅骨对中枢神经系统炎症的感知和反应
- 批准号:
10654045 - 财政年份:2022
- 资助金额:
$ 35.86万 - 项目类别:
(PQC2) Localization as a determinant of cancer dormancy
(PQC2) 定位作为癌症休眠的决定因素
- 批准号:
8876904 - 财政年份:2015
- 资助金额:
$ 35.86万 - 项目类别:
(PQC2) Localization as a determinant of cancer dormancy
(PQC2) 定位作为癌症休眠的决定因素
- 批准号:
9262173 - 财政年份:2015
- 资助金额:
$ 35.86万 - 项目类别:
Multi-wavelength femtosecond laser sources for intravital multiphoton microscopy
用于活体多光子显微镜的多波长飞秒激光源
- 批准号:
8562082 - 财政年份:2013
- 资助金额:
$ 35.86万 - 项目类别:
Multi-wavelength femtosecond laser sources for intravital multiphoton microscopy
用于活体多光子显微镜的多波长飞秒激光源
- 批准号:
8852123 - 财政年份:2013
- 资助金额:
$ 35.86万 - 项目类别:
Multi-wavelength femtosecond laser sources for intravital multiphoton microscopy
用于活体多光子显微镜的多波长飞秒激光源
- 批准号:
9087255 - 财政年份:2013
- 资助金额:
$ 35.86万 - 项目类别:
Multi-wavelength femtosecond laser sources for intravital multiphoton microscopy
用于活体多光子显微镜的多波长飞秒激光源
- 批准号:
8701293 - 财政年份:2013
- 资助金额:
$ 35.86万 - 项目类别:
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