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（CCKDs）是一种使人衰弱的疾病，治疗方法有限 available.治愈CCKD的圣杯是定义囊肿起始所必需的信号通路， 随后的维持，可以成功地用治疗剂靶向。CCKD的体外模型提供了 一个快速的研究工具，分析变化的途径，以促进细胞和蛋白质的可视化，是理想的， 发现或验证假设的起点，并且对于潜在治疗的初始测试至关重要。 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体外模型的重要性 研究方面存在着严重的障碍，阻碍了它们的高效和有效的用途：1）容易获得和共享 基于细胞的CCKD资源; 2）仔细标准化试剂，提供跨 实验室;以及3）资源中心，其促进基于细胞的创新和必需资源的产生 对于CCKD研究社区来说，无需为单个实验室带来繁琐的学习曲线， 基因组编辑、生物传感器生成和质量控制评估。核心B将在 以下目的：目的1 -建立体外生物传感器以研究儿童期涉及的信号通路 囊性肾疾病;目标2 -CCKD研究的体外基因工程模型;目标3- 建立和分发CCKD研究的关键体外资源。核心B充当重要的桥梁 联盟中的患者衍生研究（如UAB Core A）与生成的体内模型之间的差异 联合体（如UAB核心C）和治疗筛选（如UAB核心D）。具有 集中的CCKD体外生物传感器和建模资源将促进和加强更大范围的研究。 PKD社区，是对抗这种衰弱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.