This is the second renewal application for this project to understand the role of genetic changes in the pathogenesis of glomerular diseases like focal segmental glomerulosclerosis (FSGS). In this application, we propose two specific aims. In the first, we propose to characterize a gene that we discovered that is highly expressed in podocytes. This gene, ARHGAP24, is a known regulator of the actin cytoskeleton and the high expression of this gene implicates a specific actin regulatory pathway in the normal function of podocytes. To test the role of this gene in the glomerulus, we propose to generate and characterize a mouse that lacks expression of ARHGAP24. In the second aim, we will set-up a genetic screen that combines RNAi technology and state of the art mouse genetic methods to perform a genetic screen in mouse to identify genes that when mutated contribute with CD2AP and another podocyte specific gene, synaptopodin, in the pathogenesis of glomerular dysfunction. Our long-term goal is the identification of all genes that, when mutated, contribute to the pathogenesis of human FSGS.

Public Health Relevance

The goals of this project are to better understand the genetic causes of kidney disease. We will test the role of specific genes in the development of kidney diseases.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Study Section
Pathobiology of Kidney Disease Study Section (PBKD)
Program Officer
Mullins, Christopher V
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Washington University
Schools of Medicine
Saint Louis
United States
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Suleiman, Hani Y; Roth, Robyn; Jain, Sanjay et al. (2017) Injury-induced actin cytoskeleton reorganization in podocytes revealed by super-resolution microscopy. JCI Insight 2:
Beckerman, Pazit; Bi-Karchin, Jing; Park, Ae Seo Deok et al. (2017) Transgenic expression of human APOL1 risk variants in podocytes induces kidney disease in mice. Nat Med 23:429-438
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Tsuji, Kenji; P?unescu, Teodor G; Suleiman, Hani et al. (2017) Re-characterization of the Glomerulopathy in CD2AP Deficient Mice by High-Resolution Helium Ion Scanning Microscopy. Sci Rep 7:8321
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Grahammer, Florian; Wigge, Christoph; Schell, Christoph et al. (2016) A flexible, multilayered protein scaffold maintains the slit in between glomerular podocytes. JCI Insight 1:
Brähler, Sebastian; Yu, Haiyang; Suleiman, Hani et al. (2016) Intravital and Kidney Slice Imaging of Podocyte Membrane Dynamics. J Am Soc Nephrol 27:3285-3290

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