ESR11

Identification of altered signalling pathways in patients with renal ciliopathies


Renal manifestation, including nephronophthisis (NPHP), represents a major morbidity factor for ciliopathy patients for which the kidney graft is the only therapeutic issue. We developed strategies to identify molecules able to rescue ciliary phenotypes in model cell lines. We identified interesting molecules targeting a family of G protein- coupled receptor previously identified as involved in functions at primary cilium. ESR11 will characterize the expression pattern and ciliary localization of these receptors in kidney cells and their function at cilia both in vitro and in vivo, characterize the impact of NPHP mutations on these processes as well as on the signaling pathways downstream those receptors and evaluate the capacity of the drugs to ameliorates these phenotypes, using urinary epithelial renal patient cells and semi-automated fluorescence-based assays. We also aim to use in vivo models for NPH (zebrafish or mouse) and human iPSC-derived kidney and retinal organoids to validate these observations and the use of these drugs as potential new therapeutic approaches for ciliopathies.

Partner: Institut Imagine, Paris, France

Supervisor: dr A. Benmerah