Project Details
TRR 374: Tubular system and interstitium of the kidney: (Patho-)physiology and crosstalk
Subject Area
Medicine
Biology
Chemistry
Biology
Chemistry
Term
since 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 509149993
In Germany, more than 5 million patients suffer from chronic kidney disease (CKD) - most of them without knowing it - and about 100,000 require renal replacement therapy in the form of dialysis or transplantation. CKD can result from systemic diseases such as diabetes mellitus, arterial hypertension, or immune disorders, as well as from primarily intrarenal causes such as primary glomerular disease, glomerular and interstitial inflammation, inherited tubular transport defects, or polycystic kidney disease. Regardless of which cell types are primarily affected, the tubular system and interstitial cells are critically involved in many of these disease processes and tubular atrophy and interstitial fibrosis are hallmarks of CKD progression. In its first funding period, the CRC 1350 investigated the diverse functions and interplay of tubular epithelia and interstitial cells. We have gained important insights into pathomechanisms in several monogenic diseases, identified genetic risk factors in multifactorial kidney diseases, studied function and malfunction of interstitial cells, interstitial inflammation and fibrosis, and investigated damage memory and the consequences of hypoxia. For example, a team of CRC researchers uncovered the importance of TMEM16A (Ano1) chloride channels for cyst growth, confirmed the mechanism in animal models, demonstrated the efficacy of inhibitors of these channels, and finally established an ex vivo model to test the effects in human cystic kidney tissue to develop strategies for treatment of polycystic kidney patients. For the next funding period, the overall goal is to further deepen our knowledge of the (patho ) physiology of the tubular system and the renal interstitium, with a focus on developing new diagnostic and therapeutic strategies. To achieve this ambitious goal, we will incorporate further signaling pathways, new state-of-the-art methods, innovative models and analysis strategies into our research concept. For this, the transformation of CRC 1350 into TRR 374 is an important prerequisite, as this is the best way to achieve the necessary development. The research team will be further strengthened by the inclusion of outstanding (clinician) scientists, translational research projects and advanced data analysis. As TRR 374, we are well-positioned to shape nephrology research and to train the renal researchers and clinicians of the future.
DFG Programme
CRC/Transregios
Current projects
- A01 - Mechanisms of early ciliogenesis (Project Head Witzgall, Ralph )
- A02 - The impact of ROS, ferroptosis, glucose transport and IL-1 receptor signaling on the progression of ADPKD (Project Head Buchholz, Björn )
- A03 - TMEM16J in chronic kidney disease (Project Heads Kunzelmann, Karl ; Schreiber, Rainer )
- A04 - Renal ENaC regulation by the transmembrane serine protease TMPRSS2 and structure-based analysis of proteolytic channel activation (Project Heads Ilyaskin, Ph.D., Alexandr ; Korbmacher, Christoph )
- A06 - Cardio- and nephroprotective mechanisms of SGLT2 inhibition (Project Heads Maier, Lars ; Tauber, Philipp ; Wagner, Stefan )
- A07 - Proximal tubular signals as determinants of renal inflammation and fibrosis (Project Heads Warth, Richard ; Ziegler, Christine Maria )
- A08 - The role of Lipoprotein Receptor-Related Protein 1 (LRP1) in acute kidney injur (Project Heads Jobst-Schwan, Tilman ; Schiffer, Mario )
- A09 - Resolving glomerular to tubular crosstalk through miR-containing exosomes (Project Heads Müller-Deile, Janina ; Uderhardt, Stefan )
- B01 - Endocrine functions and plasticity of PDGFR-β+ interstitial cells in the healthy and fibrotic kidney (Project Heads Broeker, Katharina ; Forst, Anna-Lena )
- B02 - Urinary vesicles as signal carriers and markers of kidney function development (Project Heads Castrop, Hayo ; Heid, Iris M. )
- B04 - Phenotypic and functional characterization of pro-fibrotic and pro-regenerative T cells in models of renal fibrosis (Project Head Mack, Matthias )
- B05 - Anti-inflammatory and tissue-protective effects of 2-oxoglutarate-dependent dioxygenase inhibition in progressive kidney disease (Project Heads Jantsch, Jonathan ; Schley, Gunnar ; Willam, Carsten )
- B07 - Role of renal dendritic cell subpopulations in the inflammatory environment of acute kidney injury and kidney transplantation (Project Heads Dudziak, Diana ; Hörning, Andre ; Willam, Carsten )
- C02 - Uromodulin-NET-complement interaction in tubulointerstitial injury (Project Heads Amann, Kerstin ; Büttner-Herold, Maike ; Daniel, Christoph )
- C03 - Paracrine and endocrine communication in the renal tubulointerstitium (Project Head Schweda, Frank )
- C04 - Mechanisms of and interventional strategies against Autosomal Dominant Tubulointerstitial Kidney Diseases (ADTKD) (Project Head Wiesener, Michael )
- C05 - The epigenetic memory of renal tubular cells (Project Heads Grampp, Steffen ; Schödel, Ph.D., Johannes )
- C06 - Prioritizing genes for kidney function decline in the population and high-risk groups (Project Head Heid, Iris M. )
- C07 - Tissue K+ and Na+ distribution in renal interstitial disease assessed by 39K and 23Na MRI (Project Heads Kopp, Christoph ; Nagel, Ph.D., Armin )
- C08 - 3D-in-ovo-model to study and modulate the growth of human renal cystic tissue and mouse kidney slices (Project Heads Aung, Thiha ; Buchholz, Björn ; Härteis, Silke )
- INF - Platforms for bioinformatics methodology and GenePrioritiSation (Project Heads Behr, Merle ; Ferrazzi, Fulvia ; Heid, Iris M. )
- Z01 - Kidney imaging and ultrastructure (Project Heads Uderhardt, Stefan ; Warth, Richard ; Witzgall, Ralph )
- Z02 - Metabolomics (Project Heads Dettmer-Wilde, Katja ; Gronwald, Wolfram ; Oefner, Peter )
- Z03 - Central Task (Project Heads Schiffer, Mario ; Warth, Richard )
Completed projects
Applicant Institution
Universität Regensburg
Co-Applicant Institution
Friedrich-Alexander-Universität Erlangen-Nürnberg
Participating University
Technische Hochschule Deggendorf; Universität zu Köln
Spokespersons
Professor Dr. Mario Schiffer, since 1/2025; Professor Dr. Richard Warth, until 12/2024