Giulia is a young researcher from Italy and she holds a Bachelor’s degree in Biotechnologies at the University of Modena and Reggio Emilia and a Master’s degree in Medical and Pharmaceutical Biotechnologies at the University of Trieste. During her studies she developed a strong interest towards genetics and pathology, which she was able to follow thanks to several laboratory internships performing research on genetic diseases. During her time at the Genetics Immunology laboratory of the IRCSS Burlo Garofolo Maternal Institute (Trieste, Italy) she approached the field of immunology and translational research whereas thanks to a mobility exchange at Institut Mondor of Biomedical research (Créteil, France) she focused on genome editing techniques and cellular models. Pursuing her research interests, Giulia is currently working as a SCilS PhD student in the laboratory of hereditary kidney diseases at Imagine Institut (Paris, France).

Abstract
Nephronophthisis (NPH) is an autosomal recessive renal ciliopathy characterized by chronic tubulointerstitial nephritis with massive interstitial fibrosis and cyst formation leading to end-stage renal disease during childhood and adolescence. To date, 22 NPH causative genes have been identified and almost all the proteins encoded by these genes (NPHP) localize at the primary cilium, a particular organelle where many components of different pathways (Hedgehog, Wnt, Notch, TGF-β, GPCR, mTor, ion channels) concentrate. The aim of this project is to characterize specific signaling pathways and cellular processes altered in patients with NPH using a combination of CRISPR-based genome editing in epithelial cells and urinary epithelial cells from patients and deploy multi-omics analyses. Tubular cells invalidated for NPHP1 (one of the most mutated gene in NPH) by CRISPR-Cas technology (mIMCD3) or recovered from urine of NPHP1 patients and controls (URECs) have been established for cellular phenotyping, ciliogenesis, ciliary composition and transcriptomic analyses. A particular focus would be given to the elucidation of the inflammatory status: comparisons between NPH and other kidney diseases models will be made in order to obtain features specific for this ciliopathy. Moreover, further validations of signaling pathways will be carried in kidney organoids from patients-derived iPSC and in Nphp1 KO mice and patients kidney biopsies for more in-deep analysis of renal fibrosis development, including functional readouts epithelial differentiation, ECM deposition, ciliogenesis or ciliary trafficking. The results obtained would implement current NPH knowledge allowing to better understand the mechanisms of its pathogenesis.