Biomedical Research Core

生物医学研究核心

• 批准号: 10707954
• 负责人: GLORIA S PRYHUBER
• 金额: $ 12.1万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-21 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10707954
• 关键词: Acceleration; Adolescent; Adopted; Adult; Age; Aging; Atlases; Authorization documentation; Biological Assay; Biology; Biomedical Research; Biopsy; Cell Line; Cells; Cessation of life; Child; Childhood; Clinical; Collaborations; Communities; Consent; Data; Development; Distal; Drug toxicity; Early Diagnosis; End stage renal failure; Engineering; Ensure; FAIR principles; Generations; Gifts; Goals; Human; Hypertension; Image; Incidence; Infant; Infrastructure; Instruction; Kidney; Kidney Diseases; Kidney Failure; Knowledge; Life; Longevity; Measurement; Methods; Molecular; Morphology; Nature; Neonatal; Nephrology; Nephrons; Organ; Organ Transplantation; Organoids; Parents; Pathologic; Pathology; Patients; Pediatric Research; Physiological; Policies; Positioning Attribute; Procedures; Protocols documentation; Provider; Publishing; Quality Control; Reporter; Research; Research Personnel; Resources; Sampling; Severities; Source; Specimen; Technology; Time; Tissue Banks; Tissue Engineering; Tissue Sample; Tissues; Translational Research; Trauma; United States; Universities; Washington; authority; biological research; cell type; delivery complications; design; design verification; effective intervention; epigenome; fetal; gene function; induced pluripotent stem cell; innovation; interest; interoperability; kidney cell; kidney dysfunction; molecular imaging; multimodality; multiple omics; operation; postnatal; premature; preservation; prevent; quality assurance; repository; screening; single cell technology; tissue processing; transcriptome; validation studies

Abstract Pediatric Kidney BioMedical Core (pKidBIO Core) Kidney disease is a major cause of illness and death in infants, children, and adolescents with the incidence of end-stage kidney disease (ESKD) in these patients in the United States of about 15 per million. The rapidly increasing problems of adult hypertension and renal failure may also have roots in pediatric kidney insults that go undetected, unprevented and untreated. The development of effective interventions and methods of early detection and severity measurements of renal disease in children is lagging in part due to a lack of knowledge of physiological and pathological changes that occur as the kidney matures. Molecular blueprints would dramatically enhance our ability to design effective approaches to intervene and prevent kidney dysfunction. This goal cannot be met, however, without having a source of pediatric kidney tissue to begin molecular interrogations to identify the, uniquely human and developmental, ’omic instructions required to make and maintain healthy kidneys. The pKidBIO core, as part of the Washington University Pediatric Center of Excellence, is in an unusually strong and unique position to provide the required pediatric kidney tissues, originating from clinical biopsies or as “gifts of life” consented for research, preserved with methods shown to be compatible with the most recent technologies to enable age-specific research to dig into multi-omic single cell transcriptome and epigenome assays, molecular imaging and tissue engineering. By its design and nature, the pKidBIO core will promote enthusiasm and progress in pediatric kidney disease research by 1) providing human age-specific references for fetal and childhood kidney disease tissues, 2) enabling studies aimed to delineate cellular, morphological, physiological and molecular changes associated with postnatal kidney maturation, 3) accelerating scientific research aimed at ex vivo human kidney organoids, 4) establishing protocols for isolating differentiated kidney cell types at stages consistent with those seen in kidney tissue samples, 5) advancing drug toxicity screening, and by 6) designing validation studies of gene function and kidney engineering. The availability of the tissue and the outstanding data generated from them will attract new expertise outside kidney research developing spatial imaging and analytical technologies and research interested in physiological aging across the lifespan. The pKidBIO repository will be a national resource for the research and clinical community that is findable, accessible, interoperable, and reusable.

摘要 儿科肾脏生物医学核心（pKidBIO核心） 肾脏疾病是婴儿、儿童和青少年的疾病和死亡的主要原因， 在美国，这些患者中终末期肾病（ESKD）的发病率约为15 百万分之一成人高血压和肾衰竭的迅速增加的问题也可能有 根源在于未被发现、未被预防和未被治疗的儿童肾脏损伤。发展 有效的干预措施和方法的早期发现和严重程度的测量肾 在儿童疾病是滞后的部分原因是缺乏知识的生理和病理 肾脏成熟时发生的变化。分子蓝图将极大地增强我们的 设计有效方法干预和预防肾功能障碍的能力。这一目标 然而，如果没有儿科肾脏组织来源来开始分子治疗， 询问，以确定，独特的人类和发展，'omic指令所需的， 保持和维持健康的肾脏pKidBIO核心，作为华盛顿大学的一部分 儿科卓越中心，是在一个异常强大和独特的地位，提供 需要儿科肾脏组织，来源于临床活检或作为“生命的礼物”同意 研究，保存的方法显示与最新的技术兼容， 使年龄特异性研究能够深入到多组单细胞转录组和表观基因组 分析、分子成像和组织工程。根据其设计和性质，pKidBIO核心将 通过以下方式促进儿科肾脏疾病研究的热情和进展：1）提供人类 胎儿和儿童肾脏疾病组织的年龄特异性参考，2）使研究旨在 描绘与出生后相关的细胞、形态、生理和分子变化， 肾脏成熟，3）加速针对离体人类肾脏类器官的科学研究，4） 建立用于在与那些阶段一致的阶段分离分化的肾细胞类型的方案 在肾组织样本中观察到，5）推进药物毒性筛查，以及6）设计验证 基因功能和肾脏工程的研究。组织的可用性和突出的 由此产生的数据将吸引肾脏研究以外的新专业知识， 成像和分析技术，以及对生理老化感兴趣的研究， 寿命pKidBIO储存库将成为研究和临床的国家资源 可查找、可访问、可互操作和可重用的社区。