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Research Projects and Networks

The DRFZ participates in numerous national and international research networks, some of which we present here.

Projects funded by the German Research Foundation DFG

DFG CRC 130 - B cells: Immunity and Autoimmunity

The aim of the Transregional Collaborative Research Centre TRR130 B cells: Immunity and Autoimmunity is to gain a better understanding of the role of B lymphocytes in physiological immune reactions and in chronic inflammatory diseases.
The DRFZ contributes to this consortium with its expertise in the field of memory B lymphocytes, especially memory plasma cells, in a biomedical and clinical context.
Furthermore, it provides optical technology development, i.e. flow cytometry and intravital microscopy.

Further Information
PIs at the DRFZ:
Andreas Radbruch (Co-Speaker), Ria Baumgrass, Hyun-Dong Chang, Thomas Dörner, Andreas Grützkau, Anja Hauser, Guido Heine, Falk Hiepe, Max Löhning, Mir-Farzin Mashreghi, Raluca Niesner, Chiara Romagnani, Margita Worm

http://www.trr130.forschung.uni-erlangen.de/index.php/en/home.html

GERMANET - German Mass Cytometry Network

Mass cytometry (CyTOF technology) is a new technology that captures the complexity of cellular systems in unprecedented detail and promises significant contributions in biomedical diagnostics and research. The DRFZ initiated the establishment of the nationwide German Mass Cytometry Network GERMANET for mass cytometry in Germany: The aim is to bring together the expertise of all German mass cytometry centres.

Further Information
Contact person at the DRFZ:
Henrik Mei

DFG SPP 1937 Innate Lymphoid Cells

The DFG Priority Programme SPP 1937 Innate Lymphoid Cells is a national, interdisciplinary priority programme for the structured funding of research groups conducting joint research in the new scientific field of the Innate Lymphoid Cells (ILCs).

ILCs are a group of lymphocytes of the innate immune system discovered recently. They are important effector cells in the immune defense of infections and tumors. However, they are also involved in the pathogenesis of various inflammatory diseases such as chronic inflammatory bowel diseases, rheumatoid arthritis etc..
It is now also known that ILCs are tissue-resident cells that strongly impact on the biology of various organs and tissues.

Three research groups at the DRFZ are investigating the interaction between ILCs and the surrounding tissue in order to gain an understanding of the development of chronic inflammatory diseases.

Further Information
Contact person at the DRFZ:
Andreas Diefenbach
Chiara Romagnani
Anja Hauser

http://spp-innatelymphoidcells.de

DFG CRC 241 - Immune-Epithelial Communication in Inflammatory Bowel Diseases

The etiological background of Inflammatory Bowel Diseases (IBD: Crohn’s disease, ulcerative colitis) is still poorly understood, in particular the local cellcell interactions. The driving hypothesis behind this new joint initiative is that a dysregulated signal exchange between the epithelium and immune cells and the consequences thereof contribute to the pathogenesis of IBD.
The DRFZ focuses on how the crosstalk of intestinal microbiota and immune cells can affect intestinal barrier functions and on how mechanisms of the innate immune system can initiate inflammation or, in contrast, lead to epithelial protection and barrier repair.

PIs at the DRFZ
Hyun-Dong Chang, Andreas Diefenbach, Ahmed Hegazy, Andrey Kruglov, Andreas Radbruch, Chiara Romagnani, Antigoni Triantafyllopoulou

https://www.transregio241.de/

 

Projects funded by the German Ministry for Education and Research (BMBF)

Neuroimpa - Neuroimmunology and Pain

Musculoskeletal diseases, such as rheumatic diseases limit mobility and quality of life. Patients suffer from severe and chronic pain, which is often inadequately treated. The goal of the research network NEUROIMPA – Neuroimmunology and Pain is to investigate the role of the immune system, specifically T cells, in the development and promotion of pain in chronic joint inflammation. The overall aim of the project is to develop new therapies for the treatment of pain in chronic joint inflammation.

Further Information
Contact person at the DRFZ:
Hyun-Dong Chang
Andreas Radbruch

https://www.gesundheitsforschung-bmbf.de/de/NEUROIMPA-Neuromodulatoren-in-T-Zellen.php

PROCLAIR

The DRFZ coordinates the network PROCLAIR (“Linking Patient-Reported Outcomes with CLAims data for health services research in Rheumatology”) funded by the Ministry of Research. In cooperation with the universities of Oldenburg and Dresden as well as the Charité, data on the health care of people with inflammatory rheumatic diseases and osteoarthritis in the population has been collected. 20,000 members of the BARMER health insurance with diagnoses of rheumatoid arthritis, axial spondyloarthritis or osteoarthritis of the hip, knee or finger joints in their claims data were sent questionnaires covering symptoms, disease burden and consequences of disease. The questionnaire data were linked to the claims data. This approach combines the advantages of routine data (precise information on utilization, concomitant illnesses, therapy) with the advantages of a primary data (information from patients on disease burden and care). The data enable to assess the quality of care and the burden of illness in the population.

Further information
Contact person at the DRFZ:
Angela Zink

https://www.gesundheitsforschung-bmbf.de/de/PROCLAIR-Koordination-und-Versorgungsepidemiologie.php

Leibniz Research Alliances and Networks

Leibniz Research Alliance Bioactive Compounds and Biotechnology

Biologically active ingredients are the basis of most drugs. The aim of the research network, currently with 19 participating institutes, is to identify biological active substances, to investigate their effects and finally, to use them medically.
The main focus areas are:

  • Collection of organisms and biological materials as potential sources for new active substances
  • Isolation, analysis and chemical modification of active substances
  • Research into potential applications for biological agents::
    – for example as antibiotics, anti-inflammatories or with other medical effects
    – application in health products, nutrition and agriculture

Further information
Contact person at DRFZ:
Mir-Farzin Mashreghi

www.leibniz-wirkstoffe.de

Leibniz Research Alliance Healthy Ageing

Healthy ageing – being able to live free of disease and functional impairments for as long as possible while remaining active into old age – is an achievable goal for most older people living in industrialised societies.
The aim of the Leibniz Research Alliance (LRA) Healthy Ageing is to shed light on the biological and social mechanisms of ageing. The alliance is composed of 21 scientific institutes belonging to the Leibniz Association and has an interdisciplinary approach which allows for the analysis of the biological and social-economic factors involved in ageing. The end result will be the development of new intervention and adaption strategies for promoting healthy ageing in the long run.
The Leibniz Research Alliance Healthy Ageing also sees itself as a point of contact for policymakers and the media. Its expertise covers all issues associated with the biological, medical, social and economic aspects of ageing.
Further information
Contact person at DRFZ:
Andreas Grützkau
Andreas Radbruch

http://www.leibniz-gesundes-altern.de/en/about-us/

Leibniz Research Network Mathematical Modeling and Simulation

Socially relevant topics such as climate change, energy and health issues challenge the international research community to develop interdisciplinary and integrated approaches combining natural, life and social sciences. High information and data volumes as well as the growing importance of simulation and optimization of technological and social processes create the need for adequate and up-to-date methods for analysis and information generation. As a connecting element, modern methods of mathematical modelling and simulation (short: MMS) have proven to be a fundamental resource. For instance, they enable reliable extraction of information from large data sets, avoidance of expensive experiments, the prediction of experiments, the analysis of stochastic events and the shortening of development cycles.
The main objective of this network of 32 Leibniz Institutes of all sections is to systematically use this potential for synergies. To make the most sustainable and effective use of hard- and software resources, questions of the most suitable, fastest and most error-resistant methods are discussed.

Contact at the DRFZ
Kevin Thurley

https://www.wias-berlin.de/research/Leibniz-MMS/

Leibniz Research Network Immune-Mediated Diseases

An intact immune system protects us against infections and cancer. A malfunctioning immune system can therefore cause a wide range of diseases. In Germany, around ten percent of the population suffers from an immune-mediated disease, of which there are over 100 different types.

They include allergies, inflammatory neurological disorders, enteritis, rheumatism and diabetes. As well as weighing heavily on the patients and their families, immune-mediated diseases also have considerable economic costs. And there is still no cure for many of them — in part, because we do not fully understand them.

The aim of the Leibniz Research Network “Immune-Mediated Diseases”, coordinated by the DRFZ, is to research and explain the mechanisms underlying these diseases and to develop suitable treatments. Leibniz Institutes working in a wide range of specialist disciplines are involved in this network.

Contact at the DRFZ

Elke Luger

https://www.leibniz-gemeinschaft.de/forschung/leibniz-forschungsnetzwerke/immunvermittelte-erkrankungen.html

Projects funded by the European Commission and the European Research Council ERC

EFRE - TheraMir

The aim of the project is to establish an application laboratory for the identification of gene switches that control chronic inflammations and those that can regenerate destroyed tissue. Such gene switches, in particular regulatory ribonucleic acids and transcription factors, will be manipulated by therapeutic oligonucleotides. In cooperation with Berlin Cures GmbH, this project aims at the development of novel remission-inducing therapies using gene switches for therapies for patients with chronic inflammatory or degenerative diseases.

PI at the DRFZ
Mir-Farzin Mashreghi

This Project is funded by the European Regional Development Fund

RTCure - Rheuma Tolerance for Cure, succeeding BTCure

The European consortium RTCure – Rheuma Tolerance for Cure aims to develop therapies for patients in the earliest stages of rheumatoid arthritis (RA) and for people with a high risk of developing this disease.

The network is to develop new methods for biomonitoring the course of the disease and the treatment response. In addition, therapeutic approaches to restore immune tolerance are to be established that prevent or stop attacks by the immune system on the joints and at the same time ensure that the immune system remains capable of fending off infections. The long-term goal is to prevent or reverse the onset of RA and to cure patients in early stages of the disease.

The DRFZ leads work package 3 “Mechanisms of Immune Tolerance“ and contributes to different additional work-packages.

Further Information
Contact person at the DRFZ:
Andreas Radbruch, Hyun-Dong
Chang (coordinators WP3)
Andreas Grützkau

www.imi.europa.eu/projects-results/project-factsheets/rtcure

Projects supported by foundations

Dr. Rolf M. Schwiete Foundation

The foundation’s support has enabled the establishment of the research group “Schwiete-Laboratory for Microbiota and Inflammation“ in 2017.

Patients with chronic inflammatory diseases such as rheumatoid arthritis often have an altered intestinal flora compared to that of healthy people. Our intestinal flora is therefore an important indicator of our health status. For this reason, the research group of Hyun-Dong Chang want to find out how certain bacteria in the human intestinal flora either trigger or protect against inflammation. The aim is to develop an innovative approach that completely opens up new possibilities for the prevention and treatment of chronic inflammatory diseases and associated cancers.

Further information
Contact person at DRFZ:
Hyun-Dong Chang

The Foundation

The Dr. Rolf M. Schwiete Foundation is a non-profit foundation based in Mannheim and has existed since 22.06.2013, the anniversary of the death of Dr. Rolf M. Schwiete. He decreed that all his assets should be used, among other things, to promote research, especially in the fields of medicine and chemistry.

Link zur Stiftung

Willy Robert Pitzer Foundation

Since the end of 2015, the Willy Robert Pitzer Foundation has been funding the Pitzer Laboratory for Osteoarthritis Research at the DRFZ and the Charité – Universitätsmedizin Berlin.

Around five million people in Germany are affected by Osteoarthritis, a degenerative joint disease that often requires artificial joint replacement in the late stages of disease. Little is known about the causes of osteoarthritis and an effective therapy is not yet available. In order to better understand this disease, Max Löhning and his team are investigating the molecular processes occurring in cartilage tissue, with the long-term goal of finding ways to restore the natural regenerative ability of cartilage cells (chondrocytes).

Further information
Contact person at DRFZ:
Max Löhning

The Foundation
The Willy Robert Pitzer Foundation is a non-profit foundation under private law based in Frankfurt. Since 2001, it has been involved in numerous projects in the fields of science, health and social affairs. The founder of the foundation, architect Willy Robert Pitzer, was already strongly committed to the sick and needy during his lifetime. He died shortly after his 80th birthday in May 2003 and decreed in his will that most of his assets be transferred to the Foundation.

Willy Robert Pitzer Stiftung

The Rheumastiftung - Health care research

Endowed Chair of Health Care Research in Rheumatology

The Rheumastiftung (Rheuma Foundation) funded by the German Society for Rheumatology and the patient league Deutsche Rheuma-Liga, has been supporting this endowed professorship of Kirsten Minden since May 2015. The professorship is funded for five years and is based at the Charité-Universitätsmedizin Berlin and the German Rheumatism Research Centre.

This endowed professorship is the first major funding project of the Rheuma Foundation. Since its initiation, the professorship has contributed to the strengthening of health care research at the DRFZ as part of the epidemiology programme area. In line with the aims of the Rheumastiftung, the professorship is designed to improve the living conditions of people suffering from rheumatism with new research approaches in the field of rheumatology.

The research pursued within the scope of the professorship includes analyses of structures, processes and results of rheumatology care; the identification of care deficits; the presentation of the burden of disease of patients and their families; and the evaluation of new treatment strategies. The aim is to create a scientific basis for improving care for rheumatism patients of all age groups.

Further information
Contact person at DRFZ:

Kirsten Minden

The Rheumastiftung - Ideas Competition

Idea competition funding from Rheumastiftung (The Rheuma Foundation)

In 2011, Hyun-Dong Chang won the “Is rheumatism curable?” ideas competition for his project on the molecular adaptions of pathogenic memory T cells in chronic inflammation. In his winning project, T-lymphocytes are investigated in the context of chronic inflammation. The aim of the project is to identify molecular differences between protective and pathogenic T-lymphocytes. The concept convinced the Rheuma Foundation and follow-up financing was approved in 2016.

Further information
Contact person at DRFZ:
Hyun-Dong Chang

Die Rheumastiftung (The Rheuma Foundation) was founded on November 3, 2008 by the German Society for Rheumatology and the German Rheumatology League. This makes it the first foundation in Germany to bring together a scientific society and a patient organisation. The non-profit foundation is committed to the motto “Making rheumatism curable”. It therefore supports projects in basic and clinical research that improve the treatment of rheumatic diseases and which increase the chances of recovery.Die Rheumastiftung

Projects recently completed

DEEP - German epigenome programme

The German Epigenome Programme DEEP (2012 – 2017) has focused on the analysis of cells that play a decisive role in complex diseases with high socio-economic effects such as metabolic diseases or inflammatory diseases of the joints and intestines. Comprehensive epigenetic data from healthy and diseased cells were collected as a basis for improving clinical diagnosis, therapy and the prevention of health risks. All generated data was made publicly accessible and integrated into a sustainable worldwide data structure of the IHEC initiative (International Human Epigenome Consortium).

Further Information
Contact person at the DRFZ:
Julia Polanski

http://www.deutsches-epigenom-programm.de/

ERC IMMEMO

ERC Advanced Grant Protective and pathogenic immunological memory and its organization by stroma cells (IMMEMO)

The ERC-IMMEMO project (2011 – 2016) aimed to investigate the organization and role of immunological memory, both in protective immunity and in immune-mediated diseases on the molecular and cellular level.

Immunological memory protects us against recurrent infections, but it can also cause damaging immune responses. In chronic immune-mediated diseases, pathogenic immunological memory is likely to be a key driver of inflammation. Some of this inflammation does not respond to either the body’s own regulation, or to standard immunosuppression therapy. Chronic inflammation is therefore a particular challenge for the development of new curative therapeutic strategies.

In IMMEMO, we have developed important new concepts for the organization of immunological memory by stromal cells, as well as for the definition of resting versus active pathogenic memory.

The most relevant publications are:

  • The long-lasting T-cell memory against systemic pathogens is maintained by memory cells, which are resting in terms of division, cell migration and protein production. (Okhrimenko et al., PNAS 2014)
  • Long-lived CD8+ memory T cells remain as resting cells in the bone marrow. IL-7 produced by mesenchymal stromal cells is essential for this. (Sercan Alp et al., EJI 2015)
  • A protocol for unbiased transcriptome analysis of ex vivo isolated cells was developed. (Westendorf et al., EJI 2014)
  • The transcription factor Twist1 promotes the survival of pro-inflammatory T-helper cells of type 1 (Th1 cells) in chronically inflamed tissue. Twist1 regulates the microRNA miR-148a, which switches off the pro-apoptotic factor Bim. (Haftmann et al., EJI 2015)
  • The survival niche of memory plasma cells in the bone marrow consists of stromal cells that create a stable niche by secretion of CXCL-12. APRIL-producing eosinophils, which are subject to a constant renewal process, also contribute to the organisation of this stable niche. (Zehentmeier et al., EJI 2014)
  • A method for the targeted depletion of plasma cells according to the specificity of the (auto) antibodies they secrete was developed. (Taddeo et al., 2015)
  • Protocols for ex vivo analysis of the cytokine production of T-cells were optimized. (Zimmermann et al, EJI 2014)

We are convinced that our findings can make a decisive contribution to the development of new therapeutic strategies for immune-mediated diseases such as rheumatic and gastrointestinal inflammation, multiple sclerosis, transplant rejection or allergies.

The output of IMMEMO is a total of 30 publications and one patent. 5 PhD theses were completed.

Further Information
Contact person at the DRFZ:
Andreas Radbruch

https://erc.europa.eu/

BTCure - Be The Cure for Rheumatoid Arthritis

BTCure – Be The Cure for Rheumatoid Arthritis (2012 – 2017) was the largest European research network for the development of new therapies for rheumatoid arthritis (RA).

The aim of the network was to elucidate the molecular pathomechanisms involved in the development of RA. New targets for therapies and biomarkers for improved diagnosis were identified.

Major achievements of the DRFZ within BTCure are:

  • Identification of an inhibitory micro RNA (miR-148a) that is involved in the longevity of pathological T helper lymphocytes (Haftmann et al., 2015)
  • Development of a strategy to deplete autoantibody-secreting plasma cells (Taddeo et al., 2015)
  • Development of a standardized procedure for a genome-wide characterization of effector T cell subsets (Westendorf et al., 2014)
  • Identification of protective and pathogenic type I interferon signatures in viral infection and autoimmunity (Kyogoku et al., 2013)
  • Characterization of a new biomarker (SIGLEC-1) for monitoring disease activity in SLE (Rose et al., 2013)
  • Identification of disease-associated gene signatures in monocytes of RA and SLE patients that are potential biomarkers (Smiljanovic et al, 2012)
  • Establishment of mass cytometry (CyTOF) to identify cellular biosensors for therapy monitoring and diagnostics in blood, synovial fluid and urine samples (Baumgart et al., 2017; Schulz et al., 2017).

BTCure was funded by the Innovative Medicines Initiative (IMI), a public-private partnership between the European Union and the European Federation of Pharmaceutical Industries and Associations (EFPIA).

Further Information
Contact person at the DRFZ:
Andreas Radbruch
Hyun-Dong Chang
Andreas Grützkau

BteCure