UAB Childhood Cystic Kidney Disease Core Center (UAB-CCKDCC) - In Vitro Bioassay and Model Development Resource

摘要（核心 B） 儿童囊性肾病 (CCKD) 是一种使人衰弱的疾病，治疗方法有限 可用。治愈 CCKD 的圣杯是定义囊肿发生和形成所必需的信号通路 随后的维护可以成功地针对治疗。 CCKD 的体外模型提供 分析途径变化、促进细胞和蛋白质可视化的快速研究工具是理想的选择 发现或验证假设的起点，对于潜在治疗的初步测试至关重要。 类器官培养的最新进展提供了一种有吸引力的体内前过渡方法来理解 CCKD 和潜在治疗的第二阶段测试。尽管 CCKD 体外模型很重要 研究表明，存在阻碍其高效和有效使用的关键障碍：1）易于获取和共享 基于细胞的 CCKD 资源； 2) 仔细标准化试剂，以提供严格性和可重复性 实验室； 3) 促进创新和重要细胞资源生成的资源中心 对于 CCKD 研究界来说，不会给各个实验室带来繁琐的学习曲线负担 基因组编辑、生物传感器生成和质量控制评估。核心 B 将解决这些障碍 以下目标： 目标 1 - 建立体外生物传感器来研究童年涉及的信号通路 囊性肾病；目标 2 – 为 CCKD 研究构建体外基因工程模型；和目标 3- 至 建立并分发 CCKD 研究的关键体外资源。核心 B 充当重要桥梁 联盟中源自患者的研究（例如 UAB Core A）与生成的体内模型之间的关系 由联盟（例如UAB Core C）和治疗筛选（例如UAB Core D）。拥有一个 集中的 CCKD 体外生物传感器和建模资源将促进和加强更广泛的研究 多囊肾社区是对抗这种使人衰弱的疾病的重要组成部分。

ABSTRACT (CORE B) Childhood Cystic Kidney Diseases (CCKDs) are debilitating disorders for which there are limited treatments available. The Holy Grail to curing CCKD is to define signaling pathways essential for cyst initiation and subsequent maintenance that can be successfully targeted with therapeutics. In vitro models of CCKD provide a rapid research tool to analyze changes in pathways, to facilitate cellular and protein visualization, are ideal starting points for discovery or validation of hypotheses and are essential for initial testing of potential treatments. Recent advancements in organoid cultures provide an attractive pre-vivo transitional approach to understand CCKD and for second phase testing of potential treatments. Despite the importance of in vitro models for CCKD research there are critical barriers preventing their efficient and effective use: 1) readily available and sharable cell based CCKD resources; 2) careful standardization of reagents that provide rigor and reproducibility across laboratories; and 3) a resource center that facilitates generation of innovative and essential cell based resources for the CCKD research community, without burdening individual labs with the cumbersome learning curve of genome editing, biosensor generation, and quality control assessment. Core B will address these barriers in the following aims: Aim 1 - To Establish In Vitro Biosensors to Study Signaling Pathways Involved in Childhood Cystic Kidney Disorders; Aim 2 – To Genetically Engineer In Vitro Models for CCKD Research; and Aim 3- To Establish and Distribute Critical In Vitro Resources for CCKD Research. Core B acts as an essential bridge between the patient derived studies in the consortium (such as UAB Core A), and the in vivo models generated by the consortium (such as UAB Core C), and therapeutic screening (such as in UAB Core D). Having a centralized CCKD in vitro biosensor and modeling resource will facilitate and enhance research in the greater PKD community and is an essential component of fighting this debilitating disease.