Multiomics Analysis of Anti-Nephrin Antibody–Mediated Signaling in iPSC-Derived Podocytes
Wissenschaftliches Arbeitsprogramm
Nephrin is a key structural and signaling molecule of the slit diaphragm, essential for maintaining the integrity of the glomerular filtration barrier. In a subset of patients with minimal change disease and focal segmental glomerulosclerosis, pathogenic autoantibodies targeting Nephrin have been identified. Their presence is associated with the occurrence of nephrotic syndrome and is thought to interfere with intracellular signaling in podocytes. The project aims to systematically characterize the molecular alterations induced by anti-Nephrin antibodies and to elucidate their functional consequences for podocyte structure, metabolism, and survival. Human induced pluripotent stem cells (hiPSCs) will be genetically modified using CRISPR/Cas9 to generate NPHS1 knockout and NPHS1 overexpression lines, differentiated into podocytes, and exposed to patient sera and defined antibodies. Integrative multiomics analyses and live-cell imaging will be used to investigate signaling pathways, metabolic adaptation, and condensate formation (liquid–liquid phase separation, LLPS). The resulting data are expected to provide a detailed molecular understanding of antibody-mediated podocytopathies and to identify potential targets for future diagnostic and therapeutic approaches.