LiSyM-Krebs Partnering

Overview
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This generic project is intended to be a forum for all LiSyM partner and external stakeholders interested in participating in the BMBF initiative LiSyM-Krebs.

Programme: LiSyM-Krebs - Systemmedizinisches Forschungsnetz zur Früherkennung und Prävention von Leberkrebs

SEEK ID: https://seek.lisym.org/projects/15

Public web page: https://www.ptj.de/projektfoerderung/gesundheitsforschung/lisym-krebs

Organisms: No Organisms specified

FAIRDOM PALs: No PALs for this Project

Project created: 3rd Mar 2020

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Lars Becker

Projects: LiSyM-Krebs Partnering

Institutions: Roche Pharma AG

Thomas Berg

Projects: LiSyM-Krebs Partnering, SMART-NAFLD, DEEP-HCC network

Institutions: Universitätsklinikum Leipzig - Klinik und Poliklinik für Gastroenterologie, Sektion Hepatologie, Universität Leipzig - Sächsischer Inkubator für Klinische Translation (SIKT)

Nikolaus Berndt

Projects: LiSyM-Krebs Partnering, LiSyM network, LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi), Forschungsnetzwerk LiSyM-Krebs, DEEP-HCC network

Institutions: Charité - Universitätsmedizin Berlin, Institute of Biochemistry, Computational Systems Biochemistry Group

Johannes Bode

Mario Brosch

Projects: LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM network, LiSyM-Krebs Partnering

Institutions: Universitätsklinikum Dresden - Medizinische Klinik I, Bereich Gastroenterologie & Hepatologie

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LiSyM-Krebs - Systemmedizinisches Forschungsnetz zur Früherkennung und Prävention von Leberkrebs

LiSyM-Krebs ist ein nationales Forschungsnetz zur Früherkennung und Prävention von Leberkrebs, das unter Verwendung des systemmedizinischen Forschungsansatzes die komplexen, dynamischen Prozesse der Krankheitsprogression analysiert, um ausgehend von den Erkenntnissen aus dem Forschungsnetz LiSyM die Entstehung von Leberkrebs besser zu verstehen, vorherzusagen und im besten Fall sogar zu verhindern. LiSyM-Krebs setzt die erfolgreichen Forschungsaktivitäten der BMBF-Vorgängerprogramme ...

Projects: LiSyM-Krebs Partnering, Forschungsnetzwerk LiSyM-Krebs, SMART-NAFLD, DEEP-HCC network, C-TIP-HCC network

Web page: Not specified

Bayer AG

Country: Germany

City: 51368 Leverkusen

Web page: https://www.bayer.com/

Charité - Universitätsmedizin Berlin, Institute of Biochemistry, Computational Systems Biochemistry Group

Country: Germany

City: 10117 Berlin

Web page: https://biochemie.charite.de/

Deutsches Krebsforschungszentrum

Country: Germany

City: 69120 Heidelberg

Web page: http://www.dkfz.de

Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie

Country: Germany

City: 70376 Stuttgart

Web page: http://www.ikp-stuttgart.de

Fraunhofer Institute for Cell Therapy and Immunology - Branch Bioanalytics and Bioprocesses (IZI_BB)

Country: Germany

City: Potsdam

Web page: https://www.izi-bb.fraunhofer.de/en.html

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A hierarchical regulatory network ensures stable albumin transcription under various pathophysiological conditions

LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF), LiSyM network, LiSyM-Krebs Partnering

Abstract

Not specified

Authors: Rilu Feng, Kejia Kan, Carsten Sticht, Yujia Li, Shanshan Wang, Hui Liu, Chen Shao, Stefan Munker, Hanno Niess, Sai Wang, Christoph Meyer, Roman Liebe, Matthias P. Ebert, Steven Dooley, Huiguo Ding, Honglei Weng

Date Published: 1st Dec 2022

Publication Type: Journal

DOI: 10.1002/hep.32414

Citation: Hepatology 76(6):1673-1689

Created: 31st Jan 2023 at 09:35

FOXA2 prevents hyperbilirubinaemia in acute liver failure by maintaining apical MRP2 expression

LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF), LiSyM network, LiSyM-Krebs Partnering

Abstract (Expand)

Objective Multidrug resistance protein 2 (MRP2) is a bottleneck in bilirubin excretion. Its loss is sufficient to induce hyperbilirubinaemia, a prevailing characteristic of acute liver failure (ALF) …aracteristic of acute liver failure (ALF) that is closely associated with clinical outcome. This study scrutinises the transcriptional regulation of MRP2 under different pathophysiological conditions. Design Hepatic MRP2, farnesoid X receptor (FXR) and Forkhead box A2 (FOXA2) expression and clinicopathologic associations were examined by immunohistochemistry in 14 patients with cirrhosis and 22 patients with ALF. MRP2 regulatory mechanisms were investigated in primary hepatocytes, Fxr −/− mice and lipopolysaccharide (LPS)-treated mice. Results Physiologically, homeostatic MRP2 transcription is mediated by the nuclear receptor FXR/retinoid X receptor complex. Fxr −/− mice lack apical MRP2 expression and rapidly progress into hyperbilirubinaemia. In patients with ALF, hepatic FXR expression is undetectable, however, patients without infection maintain apical MRP2 expression and do not suffer from hyperbilirubinaemia. These patients express FOXA2 in hepatocytes. FOXA2 upregulates MRP2 transcription through binding to its promoter. Physiologically, nuclear FOXA2 translocation is inhibited by insulin. In ALF, high levels of glucagon and tumour necrosis factor α induce FOXA2 expression and nuclear translocation in hepatocytes. Impressively, ALF patients with sepsis express low levels of FOXA2, lose MRP2 expression and develop severe hyperbilirubinaemia. In this case, LPS inhibits FXR expression, induces FOXA2 nuclear exclusion and thus abrogates the compensatory MRP2 upregulation. In both Fxr −/− and LPS-treated mice, ectopic FOXA2 expression restored apical MRP2 expression and normalised serum bilirubin levels. Conclusion FOXA2 replaces FXR to maintain MRP2 expression in ALF without sepsis. Ectopic FOXA2 expression to maintain MRP2 represents a potential strategy to prevent hyperbilirubinaemia in septic ALF.

Authors: Sai Wang, Rilu Feng, Shan Shan Wang, Hui Liu, Chen Shao, Yujia Li, Frederik Link, Stefan Munker, Roman Liebe, Christoph Meyer, Elke Burgermeister, Matthias Ebert, Steven Dooley, Huiguo Ding, Honglei Weng

Date Published: 20th Apr 2022

Publication Type: Journal

DOI: 10.1136/gutjnl-2022-326987

Citation: Gut:gutjnl-2022-326987

Created: 31st Jan 2023 at 09:36

Transforming growth factor β latency: A mechanism of cytokine storage and signalling regulation in liver homeostasis and disease

LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM network, LiSyM-Krebs Partnering

Abstract

Not specified

Authors: Yujia Li, Weiguo Fan, Frederik Link, Sai Wang, Steven Dooley

Date Published: 1st Feb 2022

Publication Type: Journal

DOI: 10.1016/j.jhepr.2021.100397

Citation: JHEP Reports 4(2):100397

Created: 31st Jan 2023 at 09:31

Quantification of nematic cell polarity in three-dimensional tissues.

LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM-Krebs Partnering

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Abstract (Expand)

How epithelial cells coordinate their polarity to form functional tissues is an open question in cell biology. Here, we characterize a unique type of polarity found in liver tissue, nematic cell polarity, …

Authors: A. Scholich, S. Syga, H. Morales-Navarrete, F. Segovia-Miranda, H. Nonaka, K. Meyer, W. de Back, L. Brusch, Y. Kalaidzidis, M. Zerial, F. Julicher, B. M. Friedrich