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

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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.