LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI)
OverviewOne of the tasks of the healthy liver is to store fat. Yet, at some stage, too much fat makes the liver sick. One critical time point occurs when a healthy fatty liver becomes inflamed and progresses to steatohepatitis, or NASH. LiSyM-Pillar I will identify what events lead to this transition. Does it occur in all parts of the liver? Which molecules indicate that it is taking place? Can the degeneration be stopped or undone - and if so, how?
Programme: LiSyM: Liver Systems Medicine
SEEK ID: https://seek.lisym.org/projects/3
Public web page: http://www.lisym.org/our-work/pillar-research/zones-of-the-liver
Organisms: Mus musculus, Rattus rattus, Rattus norvegicus, Homo sapiens
FAIRDOM PALs: Vincent Moser, Lutz Brusch, Annika Schneider, Mario Brosch
Project start date: 1st Jan 2016
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Projects: LiSyM Core Infrastructure and Management (LiSyM-PD), LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi), LiSyM Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF), LiSyM network, LiSyM Scientific Leadership Team (LiSyM-LT)
Institutions: University of Freiburg - Institute of Physics, LiSyM programme directorate
https://orcid.org/0000-0002-1003-1682
Projects: LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM PALs, LiSyM network, LiSyM-Krebs Partnering, Forschungsnetzwerk LiSyM-Krebs, DEEP-HCC network
Institutions: Zentrum für Informationsdienste und Hochleistungsrechnen (ZIH), Technische Universität Dresden
https://orcid.org/0000-0003-0137-5106
Universitätsklinikum Dresden - Medizinische Klinik I, Bereich Gastroenterologie & Hepatologie
Liver Systems Medicine : striving to develop non-invasive methods for diagnosing and treating NAFLD by combining mathematical modeling and biological research. LiSyM, is a multidisciplinary research network, in which molecular and cell biologists, clinical researchers, pharmacologists and experts in mathematical modeling examine the liver in its entirety. LiSyM research focuses on the metabolic liver disease non-alcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis ...
Projects: LiSyM Core Infrastructure and Management (LiSyM-PD), LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF), LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi), Model Guided Pharmacotherapy In Chronic Liver Disease (LiSyM-MGP), Molecular Steatosis - Imaging & Modeling (LiSyM-MSIM), The Hedgehog Signalling Pathway (LiSyM-JGMMS), Multi-Scale Models for Personalized Liver Function Tests (LiSyM-MM-PLF), LiSyM PALs, Project Management PTJ, LiSyM network, LiSyM Scientific Leadership Team (LiSyM-LT)
Web page: https://www.lisym.org/
We apply multiphoton imaging, 3D digital reconstructions and computational simulations to generate spatially-resolved geometrical and functional models of human liver tissue at different stages of non-alcoholic fatty liver disease (NAFLD).
To investigate the underlying molecular principles of metabolic and morphogenic zonation of the human liver lobule, we generated an integrated epigenetic map across three zones (pericentral, intermediate and periportal) by methylation and transcriptomic analysis of hepatocytes captured by laser micro-dissection. We observe a deep link between epigenetic zonation of human liver and a zonated expression of metabolic and morphogenic pathways: Key transcriptionally zonated enzymes in xenobiotic and ...
Submitter: Mario Brosch
Studies: Integrated epigenetic map across three hepatic zones (pericentral, inte...
Assays: DNA-methylation at binding sites of uniformly expressed transcription fa..., DNA-methylation at binding sites of uniformly expressed transcription fa..., DNA-methylation at binding sites of uniformly expressed transcription fa..., Transcriptomic analysis of hepatocytes ( hepatic zone: intermediate (IZ), Transcriptomic analysis of hepatocytes ( hepatic zone: periportal (PP), Transcriptomic analysis of hepatocytes ; hepatic zone: pericentral (CV)
Histopathological analysis of human biopsies. To quantitatively characterize the transition from simple STEA to eNASH, we stained, imaged and digitally reconstructed human liver tissue in 2D and 3D from biopsies of 25 patients classified into four groups: normal control (NC, n = 6), healthy obese (HO, n = 4), steatosis (STEA, n = 8) and eNASH (n = 7).
The study comprises 19 human liver biopsy donors divided into the groups normal control (NC = 7012, 7173, 7194, 7279), healthy obese (HO = 6758, 6922, 7213, 7230, 7252), bland steatosis (STEA = 6967, 7137, 7172, 7181, 7251) and early NASH (EARLY = 6610, 7041, 7157, 7188, 7344).
Hepatocytes captured by laser microdissection were obtained from three hepatic zones (pericentral, intermediate and periportal) and subjected to reduced representation bisulfite sequencing and RNA-seq resulting in 114 ...
Submitter: Mario Brosch
Investigation: Epigenomic analysis of micro-dissected human liver
Assays: DNA-methylation at binding sites of uniformly expressed transcription fa..., DNA-methylation at binding sites of uniformly expressed transcription fa..., DNA-methylation at binding sites of uniformly expressed transcription fa..., Transcriptomic analysis of hepatocytes ( hepatic zone: intermediate (IZ), Transcriptomic analysis of hepatocytes ( hepatic zone: periportal (PP), Transcriptomic analysis of hepatocytes ; hepatic zone: pericentral (CV)
Transcriptomic analysis of hepatocytes captured by laser micro-dissection from hepatic zone: pericentral (CV)
Submitter: Mario Brosch
Assay type: RNA-seq Profiling
Technology type: Rna-seq
Investigation: Epigenomic analysis of micro-dissected human liver
DNA-methylation at binding sites of uniformly expressed transcription factors in human hepatocytes ; hepatic zone: pericentral (CV)
Submitter: Mario Brosch
Assay type: Methylation Profiling
Technology type: Technology Type
Investigation: Epigenomic analysis of micro-dissected human liver
Transcriptomic analysis of hepatocytes captured by laser micro-dissection from hepatic zone: intermediate (IZ)
Submitter: Mario Brosch
Assay type: RNA-seq Profiling
Technology type: Rna-seq
Investigation: Epigenomic analysis of micro-dissected human liver
Transcriptomic analysis of hepatocytes captured by laser micro-dissection from hepatic zone: periportal (PP)
Submitter: Mario Brosch
Assay type: RNA-seq Profiling
Technology type: Rna-seq
Investigation: Epigenomic analysis of micro-dissected human liver
DNA-methylation at binding sites of uniformly expressed transcription factors in human hepatocytes ; hepatic zone: intermediate (IZ)
Submitter: Olga Krebs
Assay type: Methylation Profiling
Technology type: Technology Type
Investigation: Epigenomic analysis of micro-dissected human liver
Creator: Fabian Segovia Miranda
Submitter: Fabian Segovia Miranda
Download
Human RNA-Seq data set GSM2819712 stored in NCBI (GEO)
Creator: Mario Brosch
Submitter: Mario Brosch
External LinkHuman RNA-Seq data set GSM2819698 stored in NCBI (GEO)
liver tissue sample : 6922_IZ_RNA
Creator: Mario Brosch
Submitter: Mario Brosch
Human RNA-Seq data set GSM2819714 stored in NCBI (GEO)
Creator: Mario Brosch
Submitter: Mario Brosch
Human RNA-Seq data set GSM2819713 stored in NCBI (GEO)
Creator: Mario Brosch
Submitter: Mario Brosch
The model is adapted from A.P. Kupinski, I. Raabe, M. Michel, D. Ail, L. Brusch, T. Weidemann, C. Bökel (2013) Phosphorylation of the Smo tail is controlled by membrane localization and is dispensable for clustering, J. Cell Sci., 126, 20, 4684-4697 https://doi.org/10.1242/jcs.128926
The model format is MorpheusML that can readily be loaded and run in Morpheus: https://morpheus.gitlab.io
Creator: Lutz Brusch
Submitter: Lutz Brusch
Model type: Ordinary differential equations (ODE)
Model format: MorpheusML
Environment: Morpheus
Model for the interaction of Wnt and Hh as published in Kolbe et al.: Mutual Zonated Interactions of Wnt and Hh Signaling Are Orchestrating the Metabolism of the Adult Liver in Mice and Human, Cell Reports, 29,4553,
Creators: Michael Kücken, Lutz Brusch
Submitters: Lutz Brusch, Michael Kücken
Model type: Partial differential equations (PDE)
Model format: MorpheusML
Environment: Morpheus
For the spatio-temporal dynamics of bile transport, bile canalicular dilation, mechanical stimulation and transduction of YAP signaling during liver regeneration see the open access publication and its appendix: Meyer et al. (2020) Bile canaliculi remodeling activates YAP via the actin cytoskeleton during liver regeneration. Molecular Systems Biology 16:e8985. https://doi.org/10.15252/msb.20198985
The model format is MorpheusML that can readily be loaded and run in the free and open source software ...
Creator: Lutz Brusch
Submitter: Lutz Brusch
Model type: Agent based modelling
Model format: MorpheusML
Environment: Morpheus
Morpheus is the modelling and simulation framework for multicellular systems biology developed at Technische Universität Dresden. Manual, examples and binaries for Windows, Linux, MacOS at: https://morpheus.gitlab.io Open source code at: https://gitlab.com/morpheus.lab/morpheus
Creators: Lutz Brusch, Jörn Starruß, Walter de Back, Andreas Deutsch
Submitter: Lutz Brusch
Model type: Agent based modelling
Model format: MorpheusML
Environment: Morpheus
Code for the bile flow model in Segovia-Miranda et al.: Three-dimensional spatially resolved geometrical and functional models of human liver tissue reveal new aspects of NAFLD progression (https://www.nature.com/articles/s41591-019-0660-7)
See the README file in the link for details installing and running the code.
Creators: Michael Kücken, Lutz Brusch
Submitter: Michael Kücken
Model type: Ordinary differential equations (ODE)
Model format: Not specified
Environment: Not specified
SOP : liver tissue microdissection for RNA sequencing
Creator: Mario Brosch
Submitter: Mario Brosch
Abstract (Expand)
Authors: Ahmed Ghallab, Maiju Myllys, Adrian Friebel, Julia Duda, Karolina Edlund, Emina Halilbasic, Mihael Vucur, Zaynab Hobloss, Lisa Brackhagen, Brigitte Begher-Tibbe, Reham Hassan, Michael Burke, Erhan Genc, Lynn Johann Frohwein, Ute Hofmann, Christian H. Holland, Daniela González, Magdalena Keller, Abdel-latif Seddek, Tahany Abbas, Elsayed S. I. Mohammed, Andreas Teufel, Timo Itzel, Sarah Metzler, Rosemarie Marchan, Cristina Cadenas, Carsten Watzl, Michael A. Nitsche, Franziska Kappenberg, Tom Luedde, Thomas Longerich, Jörg Rahnenführer, Stefan Hoehme, Michael Trauner, Jan G. Hengstler
Date Published: 1st Oct 2021
Publication Type: Journal
Abstract (Expand)
Authors: Olga Vvedenskaya, Tim Daniel Rose, Oskar Knittelfelder, Alessandra Palladini, Judith Andrea Heidrun Wodke, Kai Schumann, Jacobo Miranda Ackerman, Yuting Wang, Canan Has, Mario Brosch, Veera Raghavan Thangapandi, Stephan Buch, Thomas Züllig, Jürgen Hartler, Harald C. Köfeler, Christoph Röcken, Ünal Coskun, Edda Klipp, Witigo von Schoenfels, Justus Gross, Clemens Schafmayer, Jochen Hampe, Josch Konstantin Pauling, Andrej Shevchenko
Date Published: 1st Aug 2021
Publication Type: Journal
Abstract (Expand)
Authors: A. K. Becker, M. Dorr, S. B. Felix, F. Frost, H. J. Grabe, M. M. Lerch, M. Nauck, U. Volker, H. Volzke, L. Kaderali
Date Published: 13th Feb 2021
Publication Type: Journal
Abstract (Expand)
Authors: Lenka Belicova, Urska Repnik, Julien Delpierre, Elzbieta Gralinska, Sarah Seifert, José Ignacio Valenzuela, Hernán Andrés Morales-Navarrete, Christian Franke, Helin Räägel, Evgeniya Shcherbinina, Tatiana Prikazchikova, Victor Koteliansky, Martin Vingron, Yannis Kalaidzidis, Timofei Zatsepin, Marino Zerial
Date Published: 2021
Publication Type: Unpublished
Abstract (Expand)
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
Date Published: 11th Dec 2020
Publication Type: Journal
Talk at the Jamboree 2021 about epigenomic map of human liver zonation and loss of zonation in end-stage liver disease
Creators: Mario Brosch, Jochen Hampe, Lutz Brusch, Marino Zerial, Clemens Schafmayer
Submitter: Mario Brosch
Computational modeling and simulation become increasingly important for Systems Medicine. A number of corresponding software tools have been developed but require scientists to encode their models in an imperative programming language. Morpheus [1,2], on the other hand, is an extensible open-source software framework that is entirely based on declarative modeling. It uses the domain-specific language MorpheusML to define multicellular models through a user-friendly GUI and has since proven ...
Creators: Lutz Brusch, Michael Kücken
Submitter: Lutz Brusch
Shotgun lipidomics of microdissected periportal and pericentral zones; Characterization of NAFLD in Human Liver Biopsies by Shotgun Lipidomics
Creators: Oskar Knittelfelder, Olga Vvedenskaya
Submitter: Oskar Knittelfelder
The meeting will provide a great opportunity for discussion between modellers, experimentalists and clinicians and to organize and harmonize our future work within the LiSyM network on the grassroot level.
Start Date: 20th Nov 2017
End Date: 22nd Nov 2017
Event Website: Not specified
Country: 
Germany
City: Hünfeld
This summit will cover both the basic and translational / clinical aspects of NAFLD, with a specific focus on novel drug target and prognostic signature development.
Key sessions include all crucial pathophysiological aspects currently known to affect development and progression of NAFLD, such as "lipid metabolism and lipotoxicity" and "insulin resistance, insulin and hormonal signaling". Furthermore, oxidative stress, ER stress, and mitochondrial dysfunction will be addressed. On the second day, ...
Start Date: 9th Nov 2017
End Date: 11th Nov 2017
Event Website: https://events.easl.eu/EventPortal/Information/EventInformation.aspx?EventInformationPageCode=HOME&EventCode=nafld2017
Country: 
Italy
City: Rome
ICSB continues to be the flagship conference of the International Society for Systems Biology (ISSB). The conference will cover a variety of themes from Fundamental Biological Sciences, Network Analysis, to Metabolic Engineering and Cancer Biology. The conference will also include a variety of engaging plenary lectures, parallel sessions, poster sessions, and interactive networking opportunities.
Abstract submission deadline: May 13th, 2017
Country: 
United States
City: Blacksburg, Virginia
The International Conference on Systems Biology of Human Disease (SBHD) is a transatlantic event and communication platform for scientific exchange that takes place alternately between the United States and Germany.
SBHD 2017 is continuing a conference series launched by Peter Sorger and colleagues from Harvard Medical School in 2008. The conference focus is on mammalian systems biology, particularly on its application to human disease and therapy.
Start Date: 5th Jul 2017
End Date: 7th Jul 2017
Event Website: http://www.sbhd-conference.org/2017/index.php
Country: Germany
City: Heidelberg
This event is a jointly organized Data Management PALs Meeting that involves PALs from the German LiSyM (Liver Systems Medicine) network and from the ERASysAPP (ERA-Net for Systems Biology Applications) initiative. PALs (Project Area Liaisons) are the front line experts of the data management teams of these projects. They act as data management advocates and help gathering user requirements and testing potential data management solutions. An important part of the meeting will be to gather the ...
Country: Germany
City: 36088 Hünfeld bei Fulda
Human microdissected liver tissue sample
Published sample ID (String) *, Lab sample ID (String) *, Tissue (Controlled Vocabulary - Liver cell types) *, Organism (NCBI ID) , Sample web link (Web link) , Link to SOP used (Web link) , hepatic zone (Controlled Vocabulary - Hepatic zones in human hepatocytes) , Sample creation date (Date) , Molecule type (String)
Histopathology of human liver biopsies
PAT.ID (String) *, Diagnosis group (Controlled Vocabulary - Diagnostic groups) *, Age (Real number) ( yr ) , Sex (Controlled Vocabulary - Gender) , Weight (kg) (Real number) , BMI (String) , Diabetes Typ II (String) , Surgery indication (String) , Histology: NAS score (Real number) , Histology: NAS fat (Real number) , Histology: NAS balloning (Real number) , Histology: NAS inflammation (Real number) , Fat (Real number) ( % ) , Fibrosis (Real number) , Blood test: GGT (U/l) (Real number) , Blood test: AP (U/l) (Real number) , Blood test: total bilirubin (µmol/l) (Real number) , Blood test: ALT (U/l) (Real number) , Blood test: AST (U/l) (Real number) , Bile acids: primary (µmol/l) (Real number) , Bile acids: secondary (µmol/l) (Real number) , Bile acids: 2º/1º (Real number) , 3D reconstruction (String)
Not specified
