Browsing by Subject "podocyte"

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    A Stem Cell-Based Strategy for Modeling Human Kidney Disease and Discovering Novel Therapeutics
    (2022) Burt, Morgan Alexandra

    Chronic kidney disease (CKD) is a degenerative disorder that affects millions of people worldwide and there are no targeted therapeutics. Given the global burden and increasing prevalence of CKD, the kidneys represent an attractive target for regenerative medicine. The most severe forms of CKD involve irreversible damage to kidney glomerular podocytes - the specialized epithelial cells that encase glomerular capillaries and regulate the removal of toxins and waste from blood. Therefore, the goal of this research proposal was to develop a novel strategy to protect or promote repair of injured human kidney tissues with an initial focus on glomerular podocytes. To achieve this goal, we leveraged advances in the directed differentiation of stem cells and in vitro disease modeling techniques to develop translationally relevant human models of podocyte injury. We used these models to identify potential biomarkers of early onset podocyte dysfunction, endogenous therapeutic targets, and reno-protective drug candidates, with a particular emphasis on studying pathways implicated in biomechanical signaling. Our studies revealed that the mechanosensitive proteins YAP, CTGF, and Cyr61 may be viable endogenous therapeutic targets, while CTGF and Cyr61 expression could serve as biomarkers of podocyte mechanical integrity and cell health. Additionally, our preliminary high-throughput drug screens have identified promising podocyte-protective drug candidates, which will be the subject of future studies.

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    Genetics of Childhood Steroid Sensitive Nephrotic Syndrome: An Update.
    (Frontiers in pediatrics, 2019-01-29) Lane, Brandon M; Cason, Rachel; Esezobor, Christopher Imokhuede; Gbadegesin, Rasheed A
    Advances in genome science in the last 20 years have led to the discovery of over 50 single gene causes and genetic risk loci for steroid resistant nephrotic syndrome (SRNS). Despite these advances, the genetic architecture of childhood steroid sensitive nephrotic syndrome (SSNS) remains poorly understood due in large part to the varying clinical course of SSNS over time. Recent exome and genome wide association studies from well-defined cohorts of children with SSNS identified variants in multiple MHC class II molecules such as HLA-DQA1 and HLA-DQB1 as risk factors for SSNS, thus stressing the central role of adaptive immunity in the pathogenesis of SSNS. However, evidence suggests that unknown second hit risk loci outside of the MHC locus and environmental factors also make significant contributions to disease. In this review, we examine what is currently known about the genetics of SSNS, the implications of recent findings on our understanding of pathogenesis of SSNS, and how we can utilize these results and findings from future studies to improve the management of children with nephrotic syndrome.