TRR 57:  Organ Fibrosis: From Mechanisms of Injury to Modulation of Disease

• Subject Area: Medicine ; Biology
• Term: from 2009 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 36842431

The aim of the project is to prevent liver fibrosis by inhibiting the cell cycle of pro-fibrotic cells such as hepatic stellate cells (HSC) or immune cells. Initiation of liver fibrosis is associated with increased activity of the cell cycle protein Cyclin E1. We will investigate the function of Cyclin E1 during alcoholic liver disease (ALD), which is one of the most prevalent risk factors for liver fibrosis. We will further characterize the role of Cyclin E1 in immune cells for fibrosis initiation and develop novel anti-fibrotic treatment strategies by HSC-specific delivery of a pharmacological Cdk inhibitor.

• DFG Programme: CRC/Transregios

Completed projects

• 1 - Treatment of liver fibrosis through inhibition of the Cyclin E1/Cdk2 kinase complex (Project Heads Liedtke, Christian ;  Nevzorova, Ph.D., Yulia ;  Trautwein, Christian )
• 1 - Inflammatory and cell-death-related pathways in liver fibrosis: Cell-type specific approaches to novel therapies (Project Heads Lüdde, Ph.D., Tom ;  Trautwein, Christian )
• 1 - Defining HGF/c-Met dependent diagnostic markers and novel therapeutic targets in NASH-development (Project Heads Kroy, Daniela ;  Streetz, Konrad Ludwig ;  Zimmermann, Henning )
• 1 - Iron and a1-antitrypsin accumulation as hepatocellular initiators of liver fibrosis (Project Head Strnad, Pavel )
• 1 - Dissecting pathways initiating a profibrotic and anti-angiogenic injury response in perivascular myofibroblast precursors in kidney fibrosis (Project Head Kramann, Rafael )
• 2 - Targeting MIF family proteins in liver fibrosis: Mechanisms and translational approaches (Project Heads Bernhagen, Jürgen ;  Berres, Marie-Luise )
• 2 - Monocyte and macrophage subsets in liver fibrogenesis (Project Head Tacke, Ph.D., Frank )
• 2 - Inflammasome activation and renal fibrosis in crystal nephropathy (Project Heads Hoppe, Bernd ;  Kurts, Christian )
• 2 - Liver fibrosis in hepatic immune regulation and its impact on disease progression (Project Head Knolle, Percy Alexander )
• 2 - Role of innate lymphoid cells in liver fibrosis (Project Heads Nattermann, Jacob ;  Spengler, Ulrich )
• 2 - Role of inflammasome activation in lupus nephritis (Project Heads Latz, Eicke ;  Ludwig-Portugall, Isis )
• 2 - Inflammasome activation during cholestatic liver injury: A trigger of fibrosis progression (Project Heads Trautwein, Christian ;  Wree, Alexander )
• 2 - Impact of chronic IFN-I signalling in liver fibrosis on anti-viral immunity (Project Head Abdullah, Zeinab )
• 3 - Targeting CCN1/CYR61 as a new treatment modality in hepatic fibrosis (Project Head Weiskirchen, Ralf )
• 3 - Parietal epithelial cell activation and glomerulosclerosis: Mechanisms, mediators and clinical diagnosis (Project Heads Möller, Marcus ;  Ostendorf, Tammo )
• 3 - Angiotensin stimulated hepatic fibrogenesis and portal hypertension: Receptor regulation and intracellular signaling (Project Heads Sauerbruch, Tilman ;  Trebicka, Ph.D., Jonel )
• 3 - Cell-specific role of the PDGF system in renal fibrosis (Project Heads Boor, Ph.D., Peter ;  Floege, Jürgen )
• 3 - The effect of cell-specific deletion of Endoglin (CD105), a transmembrane auxiliary receptor for TGF-ß, on murine models of liver fibrosis (Project Head Scholten, David )
• 3 - Imaging biomarkers for staging and treatment monitoring of liver and kidney fibrosis (Project Head Lammers, Twan )
• 4 - Histopathological platform for analysis of hepatic and renal fibrosis (Project Heads Boor, Ph.D., Peter ;  Fischer, Hans-Peter ;  Franklin, Bernardo ;  Kristiansen, Glen ;  Longerich, Thomas )
• 4 - Central animal resource project (Project Head Tolba, René H. )
• 4 - FACS-based cell isolation and clinical translation (Project Heads Tacke, Ph.D., Frank ;  Weiskirchen, Ralf )
• 4 - Central Tasks of the Collaborative Research Centre (Project Head Trautwein, Christian )
• IIIP15 - The role of endocannabinoids in hepatic injury and fibrosis (Project Heads Siegmund, Sören Volker ;  Zimmer, Andreas )
• IP21 - Interplay between bacterial pyelonephritis and renal fibrosis (Project Head Engel, Daniel Robert )
• P01 - Identification and characterisation of complement factor C5 as quantitative trait gene that modifies liver fibrogenesis in mono- and polygenic mouse models (Project Heads Lammert, Frank ;  Schmitz, Volker )
• P02 - Functional and structural characterization of the PKHD1 protein Polyductin in the etiology of liver fibrosis (Project Heads Bergmann, Carsten ;  Zerres, Klaus )
• P03 - Collagen gene regulation in patients with progressive organ fibrosis due to diabetic nephropathy or IgA nephritis (Project Head Mertens, Peter Rene )
• P05 - The impact of the LIM domain proteins FHL2 and CRP2 on hepatic stellate cell activation and its crosstalk with TGF-beta signalling pathways in hepatic fibrogenesis (Project Heads Büttner, Reinhard ;  Weiskirchen, Ralf )
• P08 - The CXCR3/CXCL9 chemokine system as an antifibrotic target in murine liver fibrosis (Project Head Wasmuth, Hermann E. )
• P14 - Molecular mechanisms of renal fibrosis: analysis of the pathophysiological role of Platelet Derived Growth Factor-C (PDGF-C) (Project Heads Eitner, Frank ;  Ostendorf, Tammo )
• P19 - Mesenchymal stem cells in renal fibrosis: benefits and risks (Project Heads Floege, Jürgen ;  Kunter, Uta )

• Applicant Institution: Rheinisch-Westfälische Technische Hochschule Aachen
• Co-Applicant Institution: Rheinische Friedrich-Wilhelms-Universität Bonn
• Participating University: Ludwig-Maximilians-Universität München
• Spokesperson: Professor Dr. Christian Trautwein