MIRIAD - Multiplexed Imaging of Resilience In Alzheimers Disease
MIRIAD - Multiplexed Imaging of Resilience In Alzheimers Disease
批准号:
9439172
负责人:
Robert michael Angelo
金额:
$93.48万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-09-15 至 2022-05-31
关键词:
AbbreviationsAffectAgeAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAlzheimer&aposs disease riskAmericanAmyloid beta-ProteinApolipoprotein EAreaBiologyBlood VesselsBrainCellsCessation of lifeChronic DiseaseClinicalCognitiveColorCommunitiesConsumptionDataDatabasesDementiaDisastersDiseaseElectronsEquipmentFinancial compensationFluorescence-Activated Cell SortingFusiform gyrusGenerationsGeneticGenetic RiskGenomicsHealthcare SystemsHippocampus (Brain)HumanImageImage AnalysisImmunohistochemistryIndividualInferiorInvestigationKnowledgeLobuleLongitudinal cohort studyMeasuresModelingMolecularMultiplexed Ion Beam ImagingNerve DegenerationNeurofibrillary TanglesNeurogliaNeuronsOnline SystemsParietalPathogenicityPathologicPathway interactionsPhenotypePlant RootsPopulationProteinsProteomicsPublic HealthResearchResearch InfrastructureResistanceResolutionResourcesRiskRoleScientistSenile PlaquesSlideSpectrometry, Mass, Secondary IonSurfaceSynapsesTestingUniversitiesWashingtonabeta accumulationaging populationcollaborative approachdata sharingdisabilitydisease-causing mutationhigh dimensionalityimaging platformimaging studyinnovationinsightinstrumentationlearning strategymolecular imagingmolecular phenotypenanometerneuroinflammationneuropathologynew therapeutic targetnext generationnovelpaired helical filamentpredictive modelingpredictive signaturepresenilinpresenilin-1presenilin-2resilienceresponse to injuryrisk variantsymposiumtissue resource
中文摘要
摘要
阿尔茨海默病(AD)仍然是美国和全球主要公众残疾和死亡的主要原因
由于人口老龄化增加而造成的健康问题造成了难以形容的痛苦,并对健康构成了严峻挑战
经济和社会发展是必然的。解决方案只能来自创新研究。我们的应用程序
高度响应这一迫切的科学需求,提出利用创新的分子成像技术,
斯坦福大学发明的多路离子束成像(MIBI)平台。我们将确定高维
AD相关分子的细胞和亚细胞蛋白水平表达、相互作用和定位
通过基因组和蛋白质组学研究,使用人脑切片在恢复力和病理状态下进行鉴定
一项正在进行的AD蛋白质组学研究我们假设,在深入,阶段特异性表型
从这些独特的群体中提取的签名将提供对支持
大脑储备的保护机制。我们将通过三个具体目标来检验我们的假设:(1)建立
脆弱和抵抗大脑区域的亚细胞表型框架。下一代MIBI设备
将用于同时对30多种蛋白质进行严格成像;目标标记神经元,突触,
将同时测量非神经元细胞、神经炎症和血管成分。(2)揭示
认知弹性复合表型。使用我们成功应用于其他单一
细胞研究,我们将分析多路复用成像数据与统计深度学习方法已经
建立在我们的实验室,以确定拓扑,细胞和分子表型之间的差异弹性,共同,
病态和AD痴呆(3)实施共享数据存储库。多路复用成像在
生物学是其揭示共定位或互斥性以推断调节作用并获得机制的能力。
洞察力.为了传播我们提出的高度多路复用研究中的数百张图像,我们将创建一个
基于网络的门户网站,使用已经建立的基础设施,其中可以从本研究的所有图像
访问,多颜色叠加产生的特设,所有的功能将免费共享。
英文摘要
ABSTRACT
Alzheimer's disease (AD) remains a leading cause of disability and death in the US and major global public
health problem due to rise in aging population resulting in untold suffering, and severe challenges to health
care systems and economies is certain. Solutions will come only from innovative research. Our application is
highly responsive to this urgent scientific need by proposing to leverage an innovative molecular imaging
platform invented at Stanford, multiplexed ion beam imaging (MIBI). We will determine the high dimensional
cellular and subcellular protein-level expression, interaction, and localization for AD-relevant molecules
identified by genomic and proteomic studies in resilience and pathologic states using human brain sections
from an ongoing proteomic investigation of AD. We hypothesize that in-depth, stage-specific phenotypic
signatures extracted from these unique groups will provide insight into the modifiable factors that endorse the
protective mechanisms of brain reserve. We will test our hypothesis through three Specific Aims: (1) Establish
a subcellular, phenotypic framework of vulnerable and resistant brain areas. Next-generation MIBI equipment
will be used to rigorously image 30+ proteins simultaneously; targets marking subtypes of neurons, synapses,
non-neuronal cells, neuro-inflammatory, and vascular components will be concurrently measured. (2) Reveal
cognitive resilience multiplexed phenotypes. Using approaches we have successfully applied in other single
cell studies, we will analyze multiplexed imaging data with statistical deep learning methods already
established in our lab to identify topological, cellular, and molecular phenotypic differences among resilient, co-
morbid, and AD dementia. (3) Implement a shared data repository. The power of multiplexed imaging in
biology is its ability to reveal co-localization or mutual exclusivity to infer regulatory roles and gain mechanistic
insight. To disseminate hundreds of these images from our proposed highly multiplexed study, we will create a
web-based portal, using already established infrastructure, where all of the images from this study can be
accessed, multi-color overlays generated ad hoc, and all the features will be shared freely.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Multimodal histologic atlas of human bone marrow
-
批准号:10531005
-
项目类别:
-
资助金额:$150.0万
-
财政年份:2022
-
负责人:Robert michael Angelo
-
依托单位:
Data Analysis, Integration, and Sharing Core
-
批准号:10531006
-
项目类别:
-
资助金额:$46.44万
-
财政年份:2022
-
负责人:Robert michael Angelo
-
依托单位:
Multimodal histologic atlas of human bone marrow
-
批准号:10924351
-
项目类别:
-
资助金额:$5.0万
-
财政年份:2022
-
负责人:Robert michael Angelo
-
依托单位:
Multimodal histologic atlas of human bone marrow
-
批准号:10673893
-
项目类别:
-
资助金额:$174.52万
-
财政年份:2022
-
负责人:Robert michael Angelo
-
依托单位:
Project 2: Cellular topography and function of the breast cancer tissue microenvironment
-
批准号:10704687
-
项目类别:
-
资助金额:$34.15万
-
财政年份:2021
-
负责人:Robert michael Angelo
-
依托单位:
Project 2: Cellular topography and function of the breast cancer tissue microenvironment
-
批准号:10272390
-
项目类别:
-
资助金额:$26.33万
-
财政年份:2021
-
负责人:Robert michael Angelo
-
依托单位:
A robust platform for multiplexed, subcellular proteomic imaging in human tissue
-
批准号:9894465
-
项目类别:
-
资助金额:$59.0万
-
财政年份:2019
-
负责人:Robert michael Angelo
-
依托单位:
A robust platform for multiplexed, subcellular proteomic imaging in human tissue
-
批准号:10247827
-
项目类别:
-
资助金额:$54.7万
-
财政年份:2019
-
负责人:Robert michael Angelo
-
依托单位:
MIRIAD - Multiplexed Imaging of Resilience In Alzheimers Disease
-
批准号:9974453
-
项目类别:
-
资助金额:$87.92万
-
财政年份:2017
-
负责人:Robert michael Angelo
-
依托单位:
The Phenotypic Landscape of Cognitive Decline as Revealed by Next-Generation Multiplexed Ion Beam Imaging
-
批准号:9910356
-
项目类别:
-
资助金额:$51.42万
-
财政年份:2017
-
负责人:Robert michael Angelo
-
依托单位:
MIRIAD - Multiplexed Imaging of Resilience In Alzheimers Disease
-
批准号:10212937
-
项目类别:
-
资助金额:$86.5万
-
财政年份:2017
-
负责人:Robert michael Angelo
-
依托单位:
MIRIAD - Multiplexed Imaging of Resilience In Alzheimers Disease
-
批准号:9756278
-
项目类别:
-
资助金额:$89.33万
-
财政年份:2017
-
负责人:Robert michael Angelo
-
依托单位:
Predictive signatures in breast cancer using multiplexed ion beam imaging
-
批准号:9341982
-
项目类别:
-
资助金额:$40.13万
-
财政年份:2014
-
负责人:Robert michael Angelo
-
依托单位:
Predictive signatures in breast cancer using multiplexed ion beam imaging
-
批准号:8795909
-
项目类别:
-
资助金额:$40.13万
-
财政年份:2014
-
负责人:Robert michael Angelo
-
依托单位:
海外基金