Spatial Mapping of Proteomic and Transcriptional Signatures in Kidney Disease
肾脏疾病蛋白质组和转录特征的空间图谱
基本信息
- 批准号:10701891
- 负责人:
- 金额:$ 55.59万
- 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:2022-09-15 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:AcuteAcute Renal Failure with Renal Papillary NecrosisAlbuminuriaAnatomyAtlasesAwardBioinformaticsBiologicalBiological AssayBiological SciencesBiopsyBiopsy SpecimenCancer BiologyCellsChronic Kidney FailureClinical DataColoradoComplementCreatinineDevelopmentDiagnosisDiseaseEtiologyExpression ProfilingFundingGene ExpressionGene Expression ProfileGene Expression ProfilingGenetic Complementation TestGenetic TranscriptionGoalsHumanImmuneImmunologistImmunologyImmunotherapyInjuryInterdisciplinary StudyKidneyKidney DiseasesLocationMapsMedicalMethodsMolecularMolecular ProfilingMorbidity - disease rateMorphologyMultiplexed Ion Beam ImagingPathologic ProcessesPathologistPathway interactionsPatientsPatternPhenotypeProcessProteinsProteomicsPublic HealthRNARenal functionResearchResolutionResourcesSerumSiteStandardizationStructureSupportive careSystems BiologyTechnologyTestingTherapeuticTissue atlasTissuesTranslatingUniversitiesWidespread Diseaseanalytical methodanticancer researchcandidate markercell typeexperimental studyhemodynamicshigh dimensionalityimprovedinjury and repairinnovationinsightkidney biopsymedical schoolsmortalitymultidimensional datamultiple omicsnovelnovel diagnosticsnovel therapeutic interventionnovel therapeuticsprecision medicineprotein expressionproteomic signaturerenal damagetherapeutic targettooltranscriptometranscriptomicstumor
项目摘要
AKI and CKD are highly prevalent diseases that are associated with significant morbidity and mortality.
Unfortunately, there are not currently any specific treatments for either of these conditions. Both diseases
are caused by a range of underlying diseases and processes. AKI, for example, can result from
hemodynamic, toxic, infectious, and immune insults to the kidney. In both AKI and CKD, the diagnosis is
based on changes in the serum creatinine and albuminuria, but these tests do not discriminate among the
various etiologies of injury. Thus, beyond detecting a reduction in kidney function, clinicians typically have
little information regarding the underlying pathologic process. Better understanding of the cellular and
molecular patterns in the kidneys of patients with AKI and CKD will provide key insights into these diseases
and will lead to new diagnostic and therapeutic approaches. In recent years, multi-omics analyses have had
a major impact on our understanding of several fields, such as cancer biology, and have supported the
identification and development of new treatments. These same technologies could transform our
understanding of AKI and CKD, particularly when spatial resolution is complemented with proteomic and
transcriptomic cellular analyses. Although kidney biopsies are not usually performed in patients with AKI and
CKD, biopsy samples obtained through the Kidney Precision Medicine Project (KPMP) offer a valuable
opportunity to analyze kidney tissue using state-of-the-art high-dimensional multi-omic platforms. We
propose to utilize complementary spatial protein and RNA technologies to generate comprehensive tissue
atlases for AKI and CKD. We will pursue the following specific aims: Aim 1. Generate a kidney cellular map
via phenotypic and functional protein expression profiling. We will analyze biopsies using Multiplexed Ion
Beam Imaging (MIBI), which detects 40+ protein targets at single-cell resolution (250 nm) with tissue-specific
spatial information. Aim 2. Generate a kidney morphological map via phenotypic and functional gene
expression profiling. We will analyze biopsies using Visium Spatial Transcriptomics (ST), which provides the
whole transcriptome with morphological context. Aim 3. Generate an integrated cellular and molecular protein
and gene expression kidney atlas. We will apply statistical and bioinformatic approaches to integrate the
results from Aims 1 and 2 to create a composite map of the cellular protein and transcriptional expression
profiles in the kidney. To accomplish these goals, we have assembled a multidisciplinary research team that
includes nephrologists, renal pathologists, immunologists, and experts on multi-omics systems biology
analyses. The proposed experiments are expected to reveal subsets of AKI and CKD patients based on the
patterns of cells and molecular pathways present in the kidney, and to support identification of novel
candidate biomarkers and therapeutic targets.
AKI 和 CKD 是高度流行的疾病,与显着的发病率和死亡率相关。
不幸的是,目前还没有针对这两种情况的任何具体治疗方法。两种疾病
由一系列潜在疾病和过程引起。例如,AKI 可能是由于
对肾脏的血流动力学、毒性、感染性和免疫损伤。对于 AKI 和 CKD,诊断都是
基于血清肌酐和蛋白尿的变化,但这些测试并不区分
损伤的各种病因。因此,除了检测肾功能下降之外,临床医生通常还会
关于潜在病理过程的信息很少。更好地了解细胞和
AKI 和 CKD 患者肾脏的分子模式将为了解这些疾病提供重要见解
并将带来新的诊断和治疗方法。近年来,多组学分析
对我们对癌症生物学等多个领域的理解产生了重大影响,并支持了
识别和开发新的治疗方法。这些相同的技术可以改变我们的
了解 AKI 和 CKD,特别是当空间分辨率与蛋白质组学和
转录组细胞分析。尽管 AKI 患者通常不进行肾活检,
通过肾脏精准医学项目 (KPMP) 获得的 CKD、活检样本提供了有价值的信息
使用最先进的高维多组学平台分析肾脏组织的机会。我们
提议利用互补的空间蛋白质和RNA技术来生成综合组织
AKI 和 CKD 地图集。我们将追求以下具体目标: 目标 1. 生成肾脏细胞图谱
通过表型和功能蛋白表达谱。我们将使用多重离子分析活检
光束成像 (MIBI),可通过组织特异性以单细胞分辨率 (250 nm) 检测 40 多个蛋白质靶标
空间信息。目标 2. 通过表型和功能基因生成肾脏形态图
表达分析。我们将使用 Visium 空间转录组学 (ST) 分析活检,它提供了
具有形态学背景的整个转录组。目标 3. 生成整合的细胞和分子蛋白质
和基因表达肾图谱。我们将应用统计和生物信息学方法来整合
根据目标 1 和 2 的结果创建细胞蛋白和转录表达的复合图
肾脏中的轮廓。为了实现这些目标,我们组建了一个多学科研究团队
包括肾脏病学家、肾脏病理学家、免疫学家和多组学系统生物学专家
分析。所提出的实验预计将根据以下结果揭示 AKI 和 CKD 患者的子集:
肾脏中存在的细胞和分子途径的模式,并支持新的识别
候选生物标志物和治疗靶点。
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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{{ truncateString('WEN-YUAN E HSIEH', 18)}}的其他基金
SARS-CoV-2 Vaccine Responses in children with genetic or acquired B cell deficiencies
患有遗传性或后天性 B 细胞缺陷的儿童对 SARS-CoV-2 疫苗的反应
- 批准号:
10502936 - 财政年份:2022
- 资助金额:
$ 55.59万 - 项目类别:
SARS-CoV-2 Vaccine Responses in children with genetic or acquired B cell deficiencies
患有遗传性或后天性 B 细胞缺陷的儿童对 SARS-CoV-2 疫苗的反应
- 批准号:
10633304 - 财政年份:2022
- 资助金额:
$ 55.59万 - 项目类别:
Immune Dysregulation in Pediatric SLE Pathogenesis
儿童 SLE 发病机制中的免疫失调
- 批准号:
9223553 - 财政年份:2017
- 资助金额:
$ 55.59万 - 项目类别:
Immune Dysregulation in Pediatric SLE Pathogenesis
儿童 SLE 发病机制中的免疫失调
- 批准号:
10155413 - 财政年份:2017
- 资助金额:
$ 55.59万 - 项目类别:
Immune Dysregulation in Pediatric SLE Pathogenesis
儿童 SLE 发病机制中的免疫失调
- 批准号:
9902184 - 财政年份:2017
- 资助金额:
$ 55.59万 - 项目类别:














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