The specific objectives of ESR6 project will be to investigate: (i) the physiological regulators of UMOD production and the roles of the UMOD matrix inside the lumen of kidney tubules; (ii) the mechanisms by which UMOD mutations cause tubulointerstitial kidney disease and the role of ER/oxidative stress, unfolded protein response (UPR) and autophagy in the progression of CKD; (iii) the role of UMOD promoter variants and UMOD in complex disorders including CKD and kidney stones, and (iv) the possible benefit of pharmacological compounds interfering with UMOD production and/or processing.
- Functional characterization of the Umod gene dosage effect over time in mouse models;
- Defining the role of UMOD in different models of renal disease;
- Elucidating the mechanisms linking UMOD with the risk of CKD and hypertension;
- Validation of pathways and biomarkers studies in prospective human cohorts