We would like to get a better understanding of the deregulated molecular pathways that characterized the ADPKD. In particular, we want to have a deeper understanding of the role of HIF pathway and its downstream and upstream targets such as AspH as potential novel therapeutics targets to slow CKD progression in ADPKD.
(PKD1 KO) to test whether the inhibition of ASPH, specifically reduces Pkd1-deficient cells cell viability using a cell-based viability assay. A double PKD1/AspH knock-out mouse model will be created and murine read-out parameters (mice kidney function, kidney weight/body weight) will be measured and evaluated to determine the role of AspH in ADPKD progression. Furthermore, anti-cancer drug screening will be performed.
We expect to better define and understand the role of downstream targets of HIF-1, especially AspH in ADPKD. This knowledge could be useful to identify and/or validate new targets for drug discovery leading to more targeted treatments for ADPKD patients.