The following research goals will be addressed:
I. Identification and characterization of immune-mediated mechanisms in kidney injury
II. Development of new therapeutic strategies in experimental models
III. Validation and translation of new findings and concepts into the clinical setting
IV. Development of new diagnostic and therapeutic approaches in clinical studies
Project A1: Dr. Panzer will investigate the functional role of chemokines and chemokine receptors in TH1, TH17, and Treg-cell trafficking into (and potentially out of) the kidney, as well as the consecutive renal damage in murine models of crescentic glomerulonephritis.
Project A2: Dr. Tiegs will elucidate the immune regulatory mechanisms responsible for dampening renal inflammation.
Project A3: Dr. Steinmetz and Dr. Kluger will address the regulation of TH1 and TH17 immune responses in renal inflammation by newly emerging Treg populations and the Treg modulating cytokines IL-6 and IL-10.
Project A4: Dr. Mittrücker will investigate the antigen specific T cell response to nephritogenic antigens in experimental autoimmune glomerulonephritis and in patients with immune-mediated glomerular disease (ANCA-GN and membranous nephropathy).
Project A5: Dr. Krebs and Dr. Huber will address the plasticity of TH17 cells in glomerulonephritis. Their project aims to identify factors that induce the switch from pathogenic effector T cells to regulatory phenotypes.
Project A6: Dr. Turner will elucidate the innate and adaptive cellular sources of IL-22 and IL-9 in renal inflammation and address the functional significance of these cytokines for renal tissue injury and repair.
Project A7: Dr. Fuchs has a strong expertise in analyzing the biological functions of neutrophil extracellular traps (NETs). He will investigate the interplay of neutrophil-derived NETs and autoimmunity in murine models of systemic lupus erythematosus (SLE), and in patients with lupus nephritis.
Project A8: Dr. Kurts will investigate the pro-inflammatory and, potentially, anti-inflammatory roles of kidney dendritic cells (DCs) in glomerulonephritis by specifically focusing on their regulatory interactions with infiltrating T cells.
Project B1: Dr. Stahl and Dr. Hoxha established, together with collaborating clinicians of the KFO 228 across Germany, the largest prospectively studied cohort of patients with membranous nephropathy (MN) worldwide. Using this cohort, they established new assays for the detection and quantification of phospholipase A2 receptor (PLA2R) antibody serum levels and demonstrated that PLA2R antibody levels of patients with MN are associated with clinical activity (proteinuria) of the disease.
Project B2: The major aim of Dr. Tomas, Dr. Zahner and Dr. Stahl is the establishment of a mouse model with transgenic PLA2R expression in podocytes in which the pathogenic mechanisms underlying MN can be studied.
Project B3: Dr. Meyer-Schwesinger recently demonstrated that progressive podocyte injury in human membranous nephropathy and in murine models of podocyte injury is characterized by an early up-regulation of proteolytic systems, such as the ubiquitin proteasome system (UPS), in podocytes. Her project is designed to better understand the role of the UPS in podocyte injury and in glomerular inflammatory responses.
Project B5: Dr. Nolte will investigate the role of purinergic receptors on immune cells and kidney-resident cells in renal inflammation.
Project B6: combines the expertise of Dr. Wiech, who is a nephropathologist, and Dr. Zipfel, who is an internationally recognized specialist in the field of complement research. They aim to characterize C3 glomerulopathies by investigating the correlation of serologic and morphologic markers in patients with mutations in genes of the complement system combining the Jena MPGN collective and the Hamburg GN Registry.
Project B7: Dr. Wenzel and Dr. Ehmke will investigate the role of the innate immune system in hypertensive glomerular injury.
Project C1: Hamburg Glomerulonephritis Registry will provide a platform for all human studies of the SFB initiative.
Project C2: Management and Coordination of the CRC is the coordinating and administrating unit of the CRC.