LiSyM - Liver Systems Medicine

represents a network of twenty German centers and institutions
brought together by a 20 Million Euro funding program of the
German Government.

Introduction

LiSyM (Liver Systems Medicine) represents a research network of German centers and institutions, brought together by a 20 Million Euro funding program of the German Government, in which mathematicians, modelers, pharmacologists, molecular biologists and clinical scientists work together to develop a Systems Medicine approach to study early and advanced liver disease.

The aim of this unique research program is to acquire and use new experimental data and data from existing data bases to build computational models that facilitate decision making at the patient's bedside and to predict the actions of new medicines in the treatment of metabolic liver disease.

Research with liver tissue has a long tradition and has been the basis of the discipline of biochemistry. Over the years this research has yielded a wealth of stored quantifiable data. In Systems Medicine these data are re-used to integrate with new data as to develop multi-scale computational models that help in understanding the complexity of metabolism and its derangement in human diseases. This should lead to a more personalised type of medicine, earlier diagnosis and new therapies (Peter Jansen)

The Network

In LiSyM multidisciplinary and geographically dispersed groups are integrated into thema-oriented workgroups. We like to see LiSyM as a network in which these research groups work together, not as a consortium of independent entities, but as co-ordinated, geographically distributed teams. This requires frequent meetings and retreats were research-in-progress is discussed in an open and creative atmosphere.

Charité Universitätsmedizin Berlin

Institute for Biochemistry
Prof. Dr. Georg-Hermann Holzhütter
Institut for Radiology
Prof. Dr. Ingolf Sack
Department of General, Visceral and Thoracic Surgery
PD Dr. Martin Stockmann
Institute of Experimental Endocrinology
PD Dr. Susanna Wiegand

Humboldt Universität zu Berlin

Institute for Theoretical Biology (ITB)
Prof. Dr. Edda Klipp
Institute for Theoretical Biology (ITB)
Dr. Matthias König

Max Planck Institute for Molecular Genetics (MPI-MG)

Dr. David Michael Meierhofer

University Hospital Kiel

Department of Visceral and Thoracic Surgery
Prof. Dr. Clemens Schafmayer

Fraunhofer Institute for Medical Image Computing MEVIS

Prof. Dr. Tobias Preusser
Dr. Andrea Schenk

University Medicine Greifswald

Institute of Bioinformatics
Prof. Dr. Lars Kaderali

IfADo – Leibniz Research Centre for Working Environment and Human Factors

Department of Toxicology / Systems Toxicology
Prof. Dr. Jan G. Hengstler
Dr. Nachiket Vartak
Department of Toxicology / Systems Toxicology
Dr. Ahmed Ghallab
Department of Toxicology / Systems Toxicology
Department of Toxicology / Systems Toxicology
PD Dr. Dirk Drasdo

Heinrich Heine University

Department of Gastroenterology, Hepatology and Infectious Diseases
Prof. Dr. Johannes G. Bode

Bayer Technology Services GmbH

Dr. Lars Küpfer

RWTH Aachen University Hospital

ExMI - Experimental Molecular Imaging
Prof. Dr. Fabian Kiessling
Joint Research Center for Computational Biomedicine
Prof. Dr. Julio Saez-Rodriguez
Joint Research Center for Computational Biomedicine
Prof. Dr. Andreas Schuppert
Department of Internal Medicine III
Prof. Dr. Christian Trautwein

Saarland University Hospital

Department of Medicine II
Prof. Dr. Frank Lammert
Department of General-, Visceral-, Vascular- and Pediatric Surgery
Prof. Dr. Matthias Glanemann

University of Leipzig

Institute of Biochemistry (Faculty of Medicine)
Dr. Madlen Matz-Soja
Institute for Computer Science (Bioinformatics)
Dr. Stefan Höhme
Interdisciplinary Centre for Bioinformatics
PD Dr. Dirk Drasdo

Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG)

Prof. Dr. Marino Zerial
Dr. Andrej Shevchenko

Technical University Dresden

Center of Information Services and High Performance Computing (ZIH)
Dr. Lutz Brusch

University Hospital Carl Gustav Carus

Medical Department 1
Prof. Dr. Jochen Hampe

Medical Faculty Mannheim, Heidelberg University

Section „Molecular Hepatology – Alcohol Associated Diseases“ Dept. of Medicine II
Prof. Dr. Steven Dooley

Heidelberg University Hospital

Hamamatsu Tissue Imaging & Analysis Center
PD Dr. Niels Grabe
Department of Diagnostic and Interventional Radiology
Prof. Dr. Hans-Ulrich Kauzcor
Department of General, Visceral and Transplantation Surgery
Prof. Dr. Katrin Hoffmann

German Cancer Research Center (DKFZ)

Systems Biology of Signal Transduction (B200)
Prof. Dr. Ursula Klingmüller

HITS gGmbH

PD Dr. Wolfgang Müller

Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology

Prof. Dr. Matthias Schwab

Albert ­Ludwig University of Freiburg

Physics Institut
Prof. Dr. Jens Timmer

Helmholtz Zentrum Munich - German Research Center for Health and the Environment

Institute of Computational Biology
Prof. Dr. Dr. Fabian Theis

Technical University Munich Klinikum rechts der Isar

Institute of Molecular Immunology/Experimental Oncology
Prof. Dr. Percy A. Knolle

Scientific Pillars

Scientifically LiSyM is based on four discrete, but related Pillars, each focusing on a particular phase of disease, described by specific clinical phenomena, underpinned by experimental and theoretical studies. Taken as a whole, and looking horizontally across the Pillars, the entire package takes an integrated approach to the study of mechanisms of disease progression, from early injury to organ failure, tackling key elements of the phases of transition between each, whilst the vertical integration within each Pillar integrates studies across scales. This programme structure creates a “line of sight” from the molecular level through interactions at the cellular level, via the function of the entire organ to human beings in interaction with the environment wherein they live. To capture this in a research model, and gain a more complete understanding of these processes and interactions, a series of iterative cycles is needed at the centre of which lies computational modelling and simulation. These latter are key elements of a Systems Medicine approach.

Early Metabolic Injury

Pillar I looks into the transition from steatosis to non-alcoholic steatohepatitis (NASH) as the disease-defining moment in NAFLD. A systems analysis of these early disease events will be performed to elucidate the molecular mechanisms that trigger disease establishment.

Chronic Liver Disease Progression

Chronic liver diseases (CLD) progression leads to cirrhosis, often cancer, and ultimately to organ failure and death. Because of the complexity of this scenario, a Systems Medicine approach is chosen to develop strategies to better characterize progression and resolution of fibrosis. Pillar II aims to define key molecular mechanisms and structural changes in tissue architecture during the progression of CLD by visualizing and quantifying at a cellular level, tissue and organ scale.

Regeneration and Repair in Acute-on-Chronic Liver Failure

The incidence of this life-threatening acute-on-chronic liver failure (ACLF) is increasing, and early detection and cure are urgent clinical needs. Pillar III applies a Systems Medicine approach to identify the critical mechanisms of acute-on-chronic liver failure (ACLF) and to foster liver regeneration and repair.

Liver Function Diagnostics

Data (breath tests scores, imaging data from MRE, histopathological characterization and proteomics data of liver biopsies) will be acquired from two different groups of patients to be used in computer-assisted diagnostic tools for early detection and comprehensive evaluation of altered liver functions.