ESR10

Identification of altered signalling pathways in patients with renal ciliopathies


Renal manifestations, including nephronophthisis (NPH), are most frequent in ciliopathies and represents the morbidity factor for ciliopathy patient for which the kidney graft is the only therapeutic issue. Despite their high genetic heterogeneity, ciliopathies arise through perturbations of common cilia-dependent signaling pathways suggesting that therapeutic strategies targeting those pathways could potentially ameliorate both renal and extra-renal (i.e. retinal) alterations linked to different gene defects. ESR10 will use cellular and omics analyses (transcriptomic and proteomic) in CRISPR invalidated epithelial cells or urinary epithelial renal cells collected from patients to characterize the pathophysiological processes and determine common and specific signaling pathways altered in patients with NPH. ESR10 will use inhibitors/activators and biosensors (FRET) of the altered pathways to examine their role in NPH-associated phenotype in iPSC-derived kidney organoids and animal models (zebrafish, mouse). In collaboration with P1-RUMC and P7-EKUT, ESR10 will integrate the functional analysis and genetic data to structural and biophysical studies of ciliary assembly factors. TGFβ/BMP signalling and metabolism signaling will be analyzed in NPH models in collaboration with P2-UCPH and P4-OSR respectively.

Partner: Institut Imagine, Paris, France

Supervisor: prof dr S. Saunier