MolProt-CKD

Deciphering the molecular pathophysiology of chronic kidney disease based on tissue proteomics (MolProt-CKD)

Summary

Currently about 10% of the general population suffer from chronic kidney disease (CKD), whilst hypertension and diabetes account for 40-60% of these patients. Establishing the molecular mechanisms underlying CKD development and progression is required, as these may lead to improved patient management and more effective therapeutics. While urinary proteomics enabled the identification of an array of biomarkers for CKD, some of which are already used in clinical intervention trials, their role in CKD pathogenesis remains poorly characterized. MolProt-CKD will characterize the key proteomics molecular actors modified in renal compartments associated with the onset and progression of CKD. We will perform an in-depth proteome analysis of glomeruli or whole cortex isolated from 2 mouse models representing diabetic kidney disease (Ins2Kita-T1D model and db/db-T2D model), mimicking the key pathogenic processes leading to CKD and dialysis. We will employ state of the art LC-MS/MS proteomics analysis to generate high resolution data based on established protocols from our lab. The data will be analyzed employing appropriate statistical methods, to identify significant proteomic changes associated with early disease development. Age-associated factors will be considered in the study. Importantly, these results will then be translated to human disease through analyzing the candidate markers in human tissue specimens by immunohistochemistry. Using a Systems Medicine approach and advanced bioinformatics tools, we will combine the newly generated data with existing data on tissue transcriptomics, urinary proteomics and metabolomics available from our own datasets, collaborating consortia, and open-source databases. We will employ these data as key building blocks to generate a molecular map of CKD onset and progression. Altogether, MolProt-CKD will allow identification of the key molecular protein components in CKD, representing valuable information on disease initiation, progression and also potential therapeutic targets.

The team

Principal Investigator
Manousos Makridakis, Ph.D.

Senior Post Doctoral Researcher
Aggeliki Tserga, Ph.D.

Funding

This project has received funding from the Hellenic Foundation for Research and Innovation (HFRI) and the General Secretariat for Research and Innovation (GSRI), under grant agreement No 695.