RTF III: Individualized Cellular Models and Epigenetic Signatures of Inflammation

Coordinators: C. Klein (UzL), F.-J. Müller (CAU), P. Rosenstiel (CAU)

RTF III develops individualized disease models in cell cultures to reproduce disease processes in the laboratory. Members are working on this with what are known as human organoids. These are cell structures that emulate organs like the intestine on an individualized basis in the petri dish. They are obtained from pluripotent stem cells or directly from the patients through biopsies. With the aid of organoids, members analyze the individual disease process and test new treatment approaches in the individualized cell culture (trial-in-a-dish). The project uses state-of-the-art functional and epigenomic analysis to characterize impaired signaling pathways and differentiation patterns in people with chronic inflammatory diseases.

What does this research area’s work build on?

RTF III is based on extensive preparatory work in the field of induced pluripotent stem cells and on work with patient material aimed at investigating the effect of genetic variation on cellular function. In particular, the focus here is on epithelial cells (surface cells that cover internal and external surfaces) and neuronal cells. Innovative methods for the manipulation of primary human and murine cells (e.g. CRISPR screens) are available for use in the Cluster.

 

What are the main research objectives?

The research area is developing scalable cellular models for important diseases of the Cluster (e.g. chronic inflammatory bowel diseases, monogenic inflammatory syndromes, neuroinflammation) and also continuing to work consistently on determining cellular differentiation patterns and activity statuses with the aid of single cell sequencing. Its main objectives are to precisely determine epigenetic changes of cell types during chronic inflammation and perform high-throughput testing of treatment-related substance libraries for the correction of complex molecular phenotypes.

 

What makes this research area special?

The combination of the members’ different areas of expertise (cell biology, neurology, internal medicine, immunology, genomics) makes the research agenda of this RTF visible at an international level. A particular focus is on epigenetic mechanisms (e.g. DNA methylation) as long-term switches controlling gene expression.

 

What does this research area contribute to precision medicine in chronic inflammation?

The research area offers an interactive process within the Cluster for the effective use of patient-specific organoids and cellular models derived from hiPSC to describe individual molecular disease phenotypes. Individual impairments in regulatory networks within the framework of inflammatory diseases (e.g. due to genetic variants) can be tested at possible intervention points. The long-term plan is to develop a systematic platform that enables users to search by individualized active principles (genotype, methylation pattern) in patient cells (“clinical trial in a dish”) or even to change these cells individually in order e.g. to transplant them back into the individual patients after reprogramming their inflammation-specific methylation patterns.

 

Cooperation with other research areas in the cluster

RTF I for genetics, RTF II for microbial analysis, RTF V for the integration of proteomics and metabolomics. RTF VI for single cell analysis.

 

Members

Prof. Dr. rer. nat. Dieter Adam

Full member

UKSH Campus Kiel
Department of Immunology

Dr. Nadia Andreani

Associated member

Max Planck Institute for Evolutionary Biology
Institute of Experimental Medicine
AG Prof. Baines

Prof. Dr. John Baines

Full member

Max Planck Institute for Evolutionary Biology
Institute of Experimental Medicine
Evolutionary Genomics

Prof. Dr. med. Thorsten Bartsch

Full member

UKSH Campus Kiel
Department of Neurology

Prof. Dr. Christoph Becker-Pauly

Full member

Kiel University
Institute of Biochemistry
Degradomics of the Protease Web

Priv.-Doz. Dr. Philipp von Bismarck

Full member

UKSH Campus Kiel
Department of Pediatric and Adolescent Medicine I

Dr. Florian Bleibaum

Associated member

Kiel University
Institute of Biochemistry
Molecular Cell Biology and Transgenic Research
AG Prof. Saftig

Prof. Dr. rer. nat. Dr. h. c. Thomas Bosch

Full member

Kiel University
Institute of Zoology
Cell and Developmental Biology

Prof. Dr. Marc Ehlers

Full member

UKSH Campus Lübeck
Institute of Medical Nutrition Science
Immunology and Glycoanalytics

Prof. Dr. David Ellinghaus

Full member

Kiel University
Institute of Clinical Molecular Biology
Centre for Molecular Biosciences

Prof. Dr. Jeanette Erdmann

Full member

University of Lübeck
Institute for Cardiogenetics

Dr. rer. nat. Maren Falk-Paulsen

Associated member

Kiel University
Institute of Clinical Molecular Biology
RG Prof. Rosenstiel

Prof. Dr. rer. nat. Andre Franke

Full member

Kiel University
Institute of Clinical Molecular Biology
Genetics & Bioinformatics

Prof. Dr. Sabine Fuchs

Full member

UKSH Campus Kiel
Department of Trauma Surgery
Experimental Orthopaedics and Trauma Surgery

Prof. Dr. rer. nat. Robert Häsler

Full member

UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology

Prof. Dr. med. Dr. rer. nat. Janka Held-Feindt

Full member

UKSH Campus Kiel
Department of Neurosurgery

Prof. Dr. rer. nat. Markus Hoffmann

Full member

UKSH Campus Lübeck
Department of Dermatology, Allergology and Venerology

Dr. rer. nat. Matthias Hübenthal

Associated member

UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology
AG Prof. Weidinger

Prof. Dr. Sabrina Jabs

Full member

Kiel University
Institute of Clinical Molecular Biology

Prof. Dr. rer. biol. hum. Ottmar Janssen

Full member

UKSH Campus Kiel
Department of Immunology

Prof. Dr. med. Dietrich Kabelitz

Full member

UKSH Campus Kiel
Department of Immunology

Prof. Dr. Christoph Kaleta

Full member

UKSH Campus Kiel
Institute of Experimental Medicine
c/o Transfusion Medicine

Prof. Dr. Christine Klein

Full member

University of Lübeck
Institute of Neurogenetics

Prof. Dr. Jörg Köhl

Full member

University of Lübeck
Institute for Systemic Inflammation Research

Prof. Dr. rer. nat. Stefan Krautwald

Full member

UKSH Campus Kiel
Department of Internal Medicine IV
Department for Nephrology and Hypertension

Prof. Dr. Tanja Lange

Full member

UKSH Campus Lübeck
Department of Rheumatology and Clinical Immunology

Dr. rer. nat. Lennart T. N. Lenk

Associated member

UKSH Campus Kiel
Department of Child and Youth Medicine I

Priv.-Doz. Dr. Marcus Lettau

Full member

UKSH Campus Kiel
Department of Immunology

Prof. Dr. Ralf Ludwig

Full member

UKSH Campus Lübeck
Lübeck Institute for Experimental Dermatology
Model Systems of Inflammatory Skin Diseases

Prof. Dr. Thomas F. Meyer

Full member

UKSH Campus Kiel
Institute of Clinical Molecular Biology
Senior RG Infection Oncology

Prof. Dr. med. Oliver Müller

Full member

UKSH Campus Kiel
Department of Internal Medicine III
Translational Cardiology

Prof. Dr. med. Franz-Josef Müller

Full member

UKSH Campus Kiel
Department of Psychiatry and Psychotherapy
Center for Integrative Psychiatry gGmbH

Dr. rer. nat. Christian Peters

Associated member

UKSH Campus Kiel
Department of Immunology
AG Prof. Kabelitz

PD Dr. Aleksandar Rakovic

Full member

University of Lübeck
Institute of Neurogenetics

Prof. Dr. Karina Reiß

Full member

UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology

Prof. Dr. Gabriela Riemekasten

Full member

UKSH Campus Lübeck
Department of Rheumatology and Clinical Immunology

Prof. Dr. med. Christoph Röcken

Full member

UKSH Campus Kiel
Institute of Pathology

Prof. Dr. Stefan Rose-John

Full member

Kiel University
Institute of Biochemistry
Cytokine and Metalloproteinase Research

Prof. Dr. med. Philip Rosenstiel

Full member

Kiel University
Institute of Clinical Molecular Biology
Molecular Cell Biology

Prof. Dr. Paul Saftig

Full member

Kiel University
Institute of Biochemistry
Molecular Cell Biology and Transgenic Research

Prof. Dr. rer. nat. Susanne Sebens

Full member

UKSH Campus Kiel
Institute of Experimental Cancer Research

Dr. Philip Seibler

Full member

University of Lübeck
Institute of Neurogenetics

Prof. Dr. Bernhard Thalheim

Full member

Kiel University
Department of Computer Science
Information System Engineering

Prof. Dr. Andreas Tholey

Full member

UKSH Campus Kiel
Institute of Experimental Medicine
Systematic Proteomics

Dr. med. Florian Tran

Associated member

UKSH Campus Kiel
Department of Internal Medicine I

Prof. Dr. Stephan Weidinger

Full member

UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology

Prof. Dr. Siegfried Wolffram

Full member

Kiel University
Institute of Animal Nutrition and Physiology