PREcision Medicine through IntErrogation of Rna in the kidnEy (PREMIERE)

通过肾脏 RNA 检测实现精准医学 (PREMIERE)

• 批准号: 10242728
• 负责人: Nir Hacohen
• 金额: $ 56.09万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10242728
• 关键词: 3-Dimensional; Acute Renal Failure with Renal Papillary Necrosis; Architecture; Atlases; Bioinformatics; Biological Markers; Biomedical Research; Biopsy; Cell Extracts; Cell Lineage; Cells; Chronic Kidney Failure; Clinical; Complex; Computing Methodologies; Data; Development; Disease; Disease Marker; Excretory function; Fluid Balance; Funding; Future; Gene Expression; Gene Expression Profile; Genetic Structures; Genetic Transcription; Goals; Health; Heterogeneity; Hormonal; In Situ; In Situ Hybridization; Individual; Institution; Interdisciplinary Study; Kidney; Kidney Diseases; Laboratories; Lead; Link; Maintenance; Maps; Methods; Molecular; Molecular Analysis; Molecular Disease; Molecular Structure; Nephrons; Pathogenesis; Pathway interactions; Patients; Phase; Phenotype; Process; RNA; Renal Tissue; Reproducibility; Research Personnel; Role; Science; Site; Sodium Chloride; Source; Stains; Structure; Taxonomy; Techniques; Technology; Therapeutic; Tissue Procurements; Tissues; Work; analysis pipeline; base; biomarker development; blood pressure regulation; cell type; clinical care; data mining; design; droplet sequencing; experience; genome-wide; human tissue; improved; in silico; kidney biopsy; kidney cell; kidney dysfunction; new therapeutic target; next generation; novel; precision medicine; response; scale up; single cell analysis; single-cell RNA sequencing; targeted treatment; therapy development; tool; transcriptome sequencing; transcriptomics; wasting

ABSTRACT The kidney has developed a complex, three-dimensional architecture to serve its key functions, including excretion of waste substances, maintenance of the internal balance for fluid and salt, blood pressure control, and hormonal function. Understanding the roles of the individual renal cell types in these processes in health and disease is critical to develop novel targeted therapies. Extensive studies lead by this investigative group and others have started to identify molecular disease mechanism in renal biopsy tissues and helped to develop novel disease markers and therapies. However, up to now these studies were limited using biopsy tissue homogenates, making it difficult to discern the specific pathways activated in cell types. The PREcision Medicine through IntErrogation of Rna in the kidnEy (PREMIERE) Network will bring investigators from three leading biomedical research institutions with diverse, complementary expertise together. Our team has an established track record in working jointly to develop state of the art approaches in molecular analysis of renal disease. We will set out to mine our existing compendium of thousands of gene expression profiles from renal biopsy tissues to extract single cell signatures using advanced data mining tools. In parallel we will develop technologies in our laboratories towards single cell analysis of renal tissues and scale them down so that they can work on single cells extracted from small renal biopsies. These single cell profiles will be linked to the disease states of the patients. Key signatures associated with specific cells and diseases will be extracted and localized in the three dimensional context of the kidney using specific RNA staining techniques in the first phase of the project. In the second phase, the analytical strategies will be scaled up so that single cell profiles from specific groups of patients can be obtained in a robust and reproducible manner. To this end the PREMIERE investigators will work closely with the tissue procurement sites and the Central Hub of the KPMP, using their 20 years of experience in team science, so that at the end of the first KPMP funding cycle novel, cell type specific treatment targets are identified fueling the therapeutic pipelines of the future.

抽象的 肾脏已经开发了一种复杂的三维体系结构，以服务其关键功能，包括 废物物质排泄，维持液体和盐的内部平衡，血压 控制和激素功能。了解单个肾细胞类型在这些过程中的作用 在健康和疾病中，对于开发新颖的靶向疗法至关重要。广泛的研究由此领导 研究组和其他人已经开始鉴定肾脏活检组织中的分子疾病机制 并有助于开发新的疾病标志物和疗法。但是，到现在为止，这些研究是 使用活检组织匀浆的限制，因此难以辨别细胞中激活的特定途径 类型。 通过肾脏（首映）网络中RNA的询问的精确医学将带来 来自三个领先的生物医学研究机构的研究人员，具有多样的互补专业知识 一起。我们的团队在共同开发最新方法的共同努力方面拥有既定的往绩 在肾脏疾病的分子分析中。我们将着手挖掘我们现有的成千上万的汇编 来自肾脏活检组织的基因表达谱，使用先进数据提取单细胞特征 采矿工具。同时，我们将在实验室中开发技术来实现肾脏的单细胞分析 组织并将其缩小，以便它们可以从小型肾脏活检中提取的单个细胞进行工作。 这些单细胞谱将与患者的疾病状态有关。关键标志 特定的细胞和疾病将在肾脏的三维环境中提取并定位 在项目的第一阶段使用特定的RNA染色技术。在第二阶段，分析 将缩放策略，以便可以在A中获得特定患者组的单细胞剖面 坚固且可再现的方式。 为此，首映调查人员将与组织采购站点和中央紧密合作 毕马威（KPMP）的枢纽，利用他们在团队科学领域的20年经验，因此在第一个毕马威（KPMP）结束时 资金周期小说，鉴定出细胞类型的特定治疗目标，以加油 未来。