Research

Minimal Change Disease is characterized by nephrotic syndrome. For many patients, pathogenic antibodies against the slit-diaphragm protein Nephrin were identified in blood and biopsy samples, thereby classifying anti-Nephrin antibody-positive MCD as an autoimmune podocytopathy.
         Podocytes are specialized epithelial cells in the kidney glomerulum that wrap the glomerular capillaries with their cellular processes, called foot processes (FP) which interdigitate with the neighboring podocyte FP. Their intercellular junctions are called slit-diaphragms (SD) and constitute the outer part of the three-layered glomerular filtration barrier that keeps plasma proteins from passing into the urine. Nephrin is a major cell adhesion protein at the SD and transduces signals to the actin cytoskeleton as well as to the basement membrane. Currently, the mechanisms by which Nephrin autoantibodies induce podocytopathy are elusive.
        Our goal is to identify and understand these pathomechanisms and translate to clinical applications. We combine -omics approaches of biobank tissue and murine models with data from the Drosophila melanogaster in vivo nephrocyte model and mechanistic studies in cell culture. 

Identification of more than 30 monogenic causes of steroid resistant nephrotic syndrome (SRNS) has revealed the glomerular podocyte as the center of action in the pathogenesis of SRNS and been highly instructive in understanding functional pathways that are essential for glomerular filter function.
        NPHS1 was the first gene identified to cause SRNS and encodes the slit-diaphragm protein Nephrin which is of central importance for the slit-diaphragm. Loss of function mutations in NPHS1 cause congenital nephrotic syndrome and lead to the necessity of renal replacement therapy within the first year of life. Over 200 disease-causing mutations have been identified in NPHS1. Many missense mutations lead to proteinuria with a broad range in the age of onset from early childhood to adulthood.
        Another SRNS disease gene we are focusing on is NPHS2 which encodes the protein podocin. Podocin is a stomatin family member with a hairpin-like structure which anchors nephrin in the slit-diaphragm. The pathomechanisms of missense mutations in NPHS1 and NPHS2 are incompletely understood. We dissect these using cell culture, Drosophila and murine models.
URPP ITINERARE

Our group is interested in dissecting the mechanisms that lead to transition from acute to chronic kidney diseases. By employing several approaches such as single nucleus transcriptomics from murine models and bio-banked tissue, as well as cell culture techniques, we combine in vivo and in vitro data, to investigate the signaling pathways that govern the transition from acute to chronic kidney disease.