TRR 422:  PodoSigN – Podocyte Signaling Networks - From Basic Concepts to Disease Understanding

• Subject Area: Medicine ; Biology
• Term: since 2025
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 543604419

Podocytes form an integral part of the kidney's filtration system. They cover the outer surface of the glomerular basement membrane (GBM), closely enveloping the glomerular capillaries to facilitate the ultrafiltration of fluids, maintaining the body's internal equilibrium. These cells are particularly susceptible to injuries stemming from genetic, hemodynamic, metabolic, inflammatory, and environmental factors. Their inability to undergo cell division underscores the imperative of preserving their transcriptome, proteome, and metabolome balance throughout an organism's lifespan. Biologically, podocytes are characterized by their exquisite differentiation, adaptive responses to external signals, intricate cytoskeletal organization, and complex integrated signaling networks. From a medical perspective, the loss of podocytes plays a critical role in the most prevalent forms of chronic kidney disease (CKD). The severity of symptoms, such as albuminuria, directly corresponds to podocyte damage. Even though we know about the importance of podocyte health, therapeutic strategies still fail to address podocyte-specific diseases. Currently, the field suffers from stagnation of therapeutic developments, paired with a critically high rate of unsuccessful trials. We hypothesize that the incomplete comprehension of podocyte physiology is responsible for the lack of bench-to-bedside translation. To change this, we need to understand the complex balance of health- and injury signaling at the level of structural organization, cellular homeostasis, genetic programs, and metabolism. Recent advancements in molecular and spatial (single-cell) techniques, combined with (AI-driven) computational analytics, now enable research to advance kidney and podocyte knowledge at the complexity and integration required for next-level podocyte precision medicine. Our teams have pioneered advancements in single-cell analysis, omics technologies, multiplex imaging, and computational analytics in podocyte research. In our joint effort, we aim to systematically decode podocyte signaling maps, identify disease checkpoints, and generate knowledge graphs, integrating this information with data from our extensive national and European glomerulopathy tissue repositories. This transregional Collaborative Research Center (CRC) brings together leading experts in podocyte research from diverse disciplines, including medicine, biology, chemistry, genetics, computational science, and mathematics. Together, we will transform our understanding of podocyte-related diseases. Our 12-year perspective is to deepen the understanding of the signaling landscape of podocyte health and injury signaling (phase 1), develop integrated genome/proteome/metabolome-scale models of podocyte disease, including validated disease checkpoints (phase 2), and ultimately improve podocyte and kidney health based on targeted intervention and drug repurposing strategies (phase 3).

• DFG Programme: CRC/Transregios

Current projects

• A01 - Defending podocyte integrity against mechanical strain: Unveiling mechanosensitive multiprotein complex signaling at the slit diaphragm (Project Heads Benzing, Thomas ;  Bozek, Katarzyna ;  Butt, Linus )
• A02 - Decoding slit diaphragm stabilization (Project Heads Grahammer, Florian ;  Puelles, Ph.D., Victor G. )
• A03 - Podocyte polarity signaling: The role of the Crumbs2 complex in podocyte maturation and maintenance (Project Heads Möller-Kerutt, Annika ;  Weide, Thomas )
• A04 - Unravel the mechanotransduction signature of podocytes in health and disease (Project Heads Köhler, Sybille ;  Mühlig, Anne Katrin )
• B01 - Calcium-regulated actin organization in podocyte dysfunction and injury (Project Heads Hackl, Matthias Johannes ;  Wedlich-Söldner, Roland )
• B02 - The role of the late endosomal pathway in podocytes (Project Heads Meyer-Schwesinger, Catherine ;  Sachs, Wiebke )
• B03 - Deciphering intraglomerular inflammatory signaling in podocyte homeostasis and disease (Project Heads Brähler, Sebastian ;  Tomas, Nicola )
• B04 - Analysis of extracellular vesicles (EVs) in podocyte survival and intercellular communication (Project Heads Braun, Fabian ;  Krahn, Ph.D., Michael )
• C01 - The Ajuba/YAP/TAZ module interconnects cytoskeletal dynamics signaling and transcriptional programs to maintain podocyte homeostasis (Project Heads Cabrita Bustorff Silva, Inês ;  Schermer, Bernhard ;  Vollenbröker, Beate )
• C02 - Disruption of nuclear pores in podocyte injury (Project Heads Braun, Daniela Anne ;  Menke, Amélie Friederike )
• C03 - Genetically enhanced podocytes to uncover mechanisms of podocyte resilience (Project Heads Döser, Markus Carl ;  Pavenstädt, Hermann )
• C04 - Quantifying podocyte damage at the single-cell level and in tissue context (Project Heads Beyer, Andreas ;  Kann, Martin )
• D01 - Podocyte metabolic signaling (Project Heads Huber, Tobias B. ;  Wanner, Nicola )
• D02 - Mitochondrial control of metabolic signaling in podocytes (Project Heads Brinkkötter, Paul-Thomas ;  Ester, Lioba )
• D03 - RNA binding of metabolic enzymes in the crosstalk of metabolic regulation and signaling in podocyte disease (Project Heads Huppertz, Ina ;  Müller, Roman-Ulrich )
• D04 - Role of amino acid metabolism at the kidney filtration barrier (Project Heads Rinschen, Markus ;  Schmidt, Insa Marie )
• INFCP02 - Data management and modeling of podocyte signaling networks across clinical and molecular landscapes in human and animal systems (Project Heads Antczak, Philipp ;  Beyan, Oya ;  Bonn, Stefan )
• MGKIRTG - Integrated Research Training Group - PodoSigN-RTG (Project Heads Harendza, Sigrid ;  Meyer-Schwesinger, Catherine ;  Schermer, Bernhard ;  Weide, Thomas )
• SCP03 - Advanced molecular and clinical phenotyping (Project Heads Habbig, Sandra ;  Huber, Tobias B. ;  Lindenmeyer, Maja ;  Weber, Lutz T. ;  Wiech, Thorsten )
• ZCP01 - Central tasks and coordination of the collaborative research center (Project Head Benzing, Thomas )

• Applicant Institution: Universität zu Köln
• Co-Applicant Institution: Universität Hamburg; Universität Münster
• Participating Institution: Max-Planck-Institut für Biologie des Alterns
• Spokesperson: Professor Dr. Thomas Benzing