PEC-SURF

Kidney disease represents one of the significant global health challenges. Chronic kidney disease (CKD) affects approximately 10% of the worldwide population, with increasing prevalence and health economics impact. Its etiologies are diverse, ranging from diabetes and hypertension to infections and auto-immune processes. Injury to the glomerulus, the central filtering unit in the kidney, is involved in approximately 80%. Glomerular diseases are associated with distinct pathological lesions in the glomerulus, such as focal segmental glomerulosclerosis (FSGS) or crescentic glomerulonephritis (CrGN) involving a complex network of different glomerular cell types. Typically viewed as separate diseases, recent research indicates that these stereotypical patterns are manifestations of continuous injury and repair processes of the glomerulus and manifest independently of the underlying disease origin. The severity and nature of these patterns depend on the extent, duration, and severity of injury, as well as the reparative capacity of e.g., parietal epithelial cells, PECs. Currently, there is a significant gap in our knowledge regarding the molecular and cell-cell communication pathways of PECs. Treatment of CKD patients and their comorbidities represents a major healthcare burden, with dialysis alone costing 140 billion per year in the EU. There is an urgent medical need for more effective drugs specifically targeting severe glomerular diseases. Building on recent groundbreaking discoveries highlighting the key pathological role of PECs, we propose a series of experiments leveraging state-of-the-art technologies. In PEC-SURF, we aim to uncover new mechanisms of PEC activation, focusing on their surfaceome and analysing their cellular crosstalk. This work aims to identify promising new translatable biomarkers and therapeutic targets, which will be rigorously tested in advanced human 3D in-vitro models, glomerulus-on-chip, novel transgenic mouse models, iPSC-derived kidney organoids and human biopsy tissues.