Autosomal Dominant Tubulointerstitial Kidney Disease MUC1 (ADTKD-MUC1) is a rare genetic kidney disease that ultimately leads to end stage renal failure. Earlier studies have shown that the pathobiology of the disease involves the misdirection and intracellular accumulation of MUC1, a glycoprotein that protects the epithelial barrier. This triggers ferroptosis, a form of programmed cell death, through unknown pathways. Currently, there are no cures available, and patients rely on delaying disease progression. Therefore, due to disease rarity and lack of treatments, a new disease model is required to identify potential drug targets.
The URKIDNEY research project will utilize the access to the large cohort of ADKTD-MUC1 patients in Cyprus, to develop an accurate personalized in-vitro disease model. This will be followed by a comprehensive repurposed drug screening to identify candidates that reduce ferroptosis and intracellular accumulation of MUC1. The model will be based on kidney organoids developed by urine-derived epithelial cells differentiated into the different cell types of the nephron. This will be followed by 3D cell culture in hydrogels to allow proper tubule and epithelial barrier formation. RNA sequencing analysis will identify deregulated pathways and a high-throughput drug screening will be performed at our collaborative institute (BIU) for selecting promising drugs.
The project has the potential to generate a powerful, patient-specific tool for studying kidney diseases, with ADKTD-MUC1 serving as a starting point. This would provide a vital framework in Cyprus for future projects and the creation of a competitive startup company that specializes in precision medicine. The proposed research and training program will complement the applicant’s skills in 3D cell cultures with the host’s expertise in bioinformatics to enhance his professional development and facilitate new international research and innovation initiatives and multidisciplinary collaborations.
The URKIDNEY research programme is funded by the Research and Innovation Foundation under the “Horizon Europe – 2nd Opportunity – MSCA” programme (OPPORTUNITY – MSCA/1223).

 

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