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

摘要(核心B) 儿童囊性肾脏疾病(CCKD)是一种治疗方法有限的衰弱疾病 可用。治愈CCKD的圣杯是定义囊性起始和 可以成功地通过治疗学进行的后续维护。CCKD的体外模型提供 一种分析通路变化的快速研究工具，以促进细胞和蛋白质的可视化是理想的 这是发现或验证假说的起点，也是初步测试潜在治疗方法的关键。 有机物培养的最新进展提供了一种诱人的体内前过渡方法来理解 CCKD和潜在治疗的第二阶段测试。尽管体外模型在CCKD中的重要性 研究存在阻碍其高效和有效使用的关键障碍：1)容易获得和共享 基于细胞的CCKD资源；2)试剂的仔细标准化，以提供严密性和重复性 实验室；以及3)资源中心，促进创新和基于细胞的必要资源的产生 对于CCKD研究社区，不会给各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与儿童有关的信号通路 囊性肾脏疾病；目标2--对CCKD研究的体外模型进行基因工程；以及目标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 患者在该联盟中进行的研究(如UAB Core A)与生成的体内模型之间的关系 通过联合体(如UAB Core C)和治疗性筛查(如UAB Core D)。拥有一个 集中化的CCKD体外生物传感器和建模资源将在更大程度上促进和加强研究 PKD社区，是抗击这一令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.