Pathophysiology of podocyte damage

The glomerulus is a specialized structure in the kidney cortex that is responsible for the production of primary urine. The glomerular filtration barrier is a selective macromolecular filter composed of the fenestrated endothelium, the glomerular basement membrane, and terminally differentiated epithelial cells called podocytes. A key characteristic of healthy podocytes is the presence of a network of interdigitating membranous projections, called foot processes, that form a highly specialized filtration structure known as the slit diaphragm. All of this complex cell morphology is supported by a highly dynamic and tightly regulated cytoskeleton, alongside numerous other signaling molecules and interacting proteins. A common observation in clinical syndromes that affect the glomerular filter is the loss of these specialized cell-to-cell contacts, which in almost all cases leads to proteinuria. However, although glomerular diseases are a leading cause of end-stage renal failure, there are currently no specific therapy options available to target injured podocytes.

The Schiffer research group aims to identify peptides and small molecules capable of targeting the podocytes and modulating critical aspects of the cytoskeleton to develop novel clinical strategies to treat podocytopathies. We also focus on describing the underlying molecular mechanisms responsible for podocyte dysfunction. To accomplish this, we rely on well-established glomerular cell lines, as well as zebrafish and mice, to model different aspects of glomerular function. Additionally, we use information derived from big “-omics” datasets, as well as specific cell biology experiments, to address a variety of basic podocyte biology and clinically relevant translational research questions.