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: 10703510
• 负责人: Nir Hacohen
• 金额: $ 62.74万
• 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 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10703510
• 关键词: 3-Dimensional; Acute Renal Failure with Renal Papillary Necrosis; Address; Anatomy; Architecture; Automobile Driving; Bioinformatics; Biological Markers; Biomedical Research; Biopsy; CRISPR/Cas technology; Cell Communication; Cell physiology; Cells; Cellular biology; Chronic Kidney Failure; Cohort Studies; Communities; Complex; Consensus; Core Biopsy; Data; Data Set; Development; Diabetic Nephropathy; Dimensions; Disease; Disease Marker; Disease Pathway; Environment; Event; Excretory function; Fluid Balance; Fluorescent in Situ Hybridization; Funding; Future; Gene Expression; Genes; Genetic Transcription; Health; Heterogeneity; Hormonal; Immune; Immunology; Individual; Injury to Kidney; Institution; Kidney; Kidney Diseases; Kidney Transplantation; Knowledge; Lead; Length; Link; Lupus Nephritis; Maintenance; Maps; Messenger RNA; Methods; Mitochondria; Molecular; Molecular Analysis; Molecular Biology; Molecular Disease; Nephrology; Nephrons; Participant; Pathology; Pathway interactions; Patients; Prevention strategy; Process; Protein Isoforms; Protocols documentation; Public Health; Quality Control; RNA; RNA Splicing; Reproducibility; Research; Research Personnel; Resolution; Role; Science; Site; Sodium Chloride; Stains; Structure; Subgroup; Systems Biology; Techniques; Technology; Therapeutic; Tissue Procurements; Tissue atlas; Tissues; Transcript; Work; analysis pipeline; blood pressure control; cell type; clinical care; cost; data mining; differential expression; experience; improved; insight; interstitial; kidney biopsy; kidney cell; multidisciplinary; nanopore; new therapeutic target; novel; patient subsets; precision medicine; preservation; quality assurance; scale up; single-cell RNA sequencing; therapeutic biomarker; tissue injury; tool; 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 and cell states 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. The PREcision Medicine through IntErrogation of Rna in the kidnEy (PREMIERE) Network has brought 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 continue to perform high-quality, high-throughput single cell RNA sequencing on research biopsies from the Kidney Precision Medicine Project and advance the technology for deeper sequence coverage, reduce cost, use smaller biopsy portions without data loss so that additional technologies can be employed across KPMP, in a robust and reproducible manner. 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 spatial context of the kidney using specific, highly multiplexed RNA staining techniques. Additionally, we will employ cutting edge spatial transcriptomic technology to map cell clusters to their local environment for an added dimension of disease understanding. 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 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 排泄废物物质，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和细胞态在这些中的作用 健康和疾病的过程对于开发新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。通过审讯的精确医学 肾脏（Premiere）网络中的RNA带来了来自三项领先生物医学研究的研究者 具有多样化的补充专业知识的机构。我们的团队在 共同致力于开发肾脏疾病分子分析的艺术方法。我们将继续 在肾脏的研究活检中进行高质量的高通量单细胞RNA测序 精密医学项目并推进技术的更深序列覆盖，降低成本，使用 较小的活检部分而没有数据丢失，因此可以在kpmp的跨度中采用其他技术 坚固且可再现的方式。这些单细胞谱将与患者的疾病状态有关。 与特定细胞和疾病相关的关键特征将在空间环境中提取和本地化 使用特定的，高度多重的RNA染色技术的肾脏。此外，我们将采用切割 边缘空间转录组技术将细胞簇映射到其本地环境以增加维度 理解疾病。为此，首映调查人员将与组织紧密合作 采购网站和毕马威会计师事务所的中心枢纽，利用他们在团队科学领域的20年经验，因此 在毕马威（KPMP）资金周期结束时 未来的治疗管道。

项目成果

Molecular Signatures of Glomerular Neovascularization in a Patient with Diabetic Kidney Disease.

糖尿病肾病患者肾小球新生血管形成的分子特征。

• DOI: 10.2215/cjn.0000000000000276
• 发表时间: 2023
• 期刊: Clinical journal of the American Society of Nephrology : CJASN
• 作者: Ferkowicz,MichaelJ;Verma,Ashish;Barwinska,Daria;Ferreira,RicardoMelo;Henderson,JoelM;Kirkpatrick,Mary;Silva,PaoloS;Steenkamp,DevinW;Phillips,CarrieL;Waikar,SushrutS;Sutton,TimothyA;KidneyPrecisionMedicineProject
• 通讯作者: KidneyPrecisionMedicineProject