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GvHDCure SIGNED

Understanding the dynamics of the immune system to cure graft-versus-host disease (GvHD).

Total Cost €

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EC-Contrib. €

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Partnership

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 Outcomes and results

 GvHDCure project word cloud

Explore the words cloud of the GvHDCure project. It provides you a very rough idea of what is the project "GvHDCure" about.

rna    events    multiple    genomic    cancer    therapeutic    phospho    array    graft    function    genetic    allogeneic    validated    inflammation    reticulum    strategies    tissue    safe    effector    quantitative    precise    manipulate    epithelial    selectively    combination    enterocyte    dendritic    mirs    disease    patients    activation    death    murine    mice    kinases    imaging    immune    transplantation    inhibitors    acute    propagating    endoplasmic    cre    mouse    host    undergone    critical    gvhd    infiltration    vivo    bank    gene    pathophysiological    levels    micro    sensing    intestinal    regulatory    lines    verification    mir    individualized    reporter    injury    data    continuous    neutrophil    hematopoietic    organoid    versus    allo    damps    transgenic    lox    mechanisms    cells    event    neutrophils    molecular    apoptosis    programs    hct    stress    isolate    bacterial    efficient    initiation    mortality    maintenance    pathogenesis    kinase    screening    fingerprint    found    translocation    defects    mrna    enterocytes    selective    molecules    track    interfere    blood    analyze    splicing    er    systematically    culture    cell    xbp    relies    earliest    propagate    proteomics    human    gvhdcure    tract    networks    connection    intestines    initiate   

Project "GvHDCure" data sheet

The following table provides information about the project.

Coordinator		 UNIVERSITAETSKLINIKUM FREIBURG 

Organization address
address: HUGSTETTER STRASSE 49
city: FREIBURG
postcode: 79106
website: n.a.

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.
 Coordinator Country Germany [DE]
 Project website https://www.bioss.uni-freiburg.de/prof-dr-robert-zeiser/
 Total cost 1˙987˙500 €
 EC max contribution 1˙987˙500 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-CoG
 Funding Scheme ERC-COG
 Starting year 2016
 Duration (year-month-day) from 2016-03-01   to  2021-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAETSKLINIKUM FREIBURG DE (FREIBURG) coordinator 1˙987˙500.00

Map

 Project objective

Acute graft-versus-host disease (GvHD) is the leading cause of the high mortality of patients having undergone allogeneic hematopoietic cell transplantation. A key event in the pathogenesis of GvHD is the injury and loss of epithelial cells in the intestinal tract. The overall goal of GvHDCure is to identify the pathophysiological mechanisms that initiate (1), propagate (2) and maintain (3) GvHD. (1) We found that one of the earliest events during GvHD initiation is infiltration of the intestines by neutrophils. By using transgenic neutrophil cell lines carrying selective gene defects, we will systematically evaluate molecules in neutrophils that are critical for their sensing and effector function during GvHD in combination with novel imaging methods to track bacterial translocation. (2) The molecular programs propagating inflammation-induced epithelial apoptosis, endoplasmic reticulum stress and the sensing of DAMPs in GvHD are not understood. We will isolate enterocytes from GvHD mice to develop a precise quantitative genomic and micro RNA (miR) fingerprint of their death. The connection between ER stress and enterocyte death will be validated in intestinal organoid culture systems and in vivo in an XBP-1 mRNA splicing reporter mouse. In addition, we will make use of our human tissue bank, allowing the efficient genetic screening and verification of regulatory molecular networks in the cells from GvHD patients. (3) Maintenance of GvHD relies on continuous immune cell activation. Based on our miR array and phospho-proteomics data set, we will selectively analyze the role of several miRs and kinases in neutrophils, dendritic cells, T cells and enterocytes for GvHD maintenance by using multiple Cre-lox mice and kinase inhibitors to manipulate GvHD. Via a combination of murine and human studies GvHDCure aims to directly develop individualized therapeutic strategies to interfere with GvHD at multiple levels to make allo-HCT more safe for patients with blood cancer.

 Publications

year authors and title journal last update
List of publications.
2017 N Stickel, K Hanke, D Marschner, G Prinz, M Köhler, W Melchinger, D Pfeifer, A Schmitt-Graeff, T Brummer, A Heine, P Brossart, D Wolf, N von Bubnoff, J Finke, J Duyster, J Ferrara, U Salzer, R Zeiser
MicroRNA-146a reduces MHC-II expression via targeting JAK/STAT signaling in dendritic cells after stem cell transplantation
published pages: 2732-2741, ISSN: 0887-6924, DOI: 10.1038/leu.2017.137 		Leukemia 31/12 2019-06-19
2018 Jan Hülsdünker, Katja J. Ottmüller, Hannes P. Neeff, Motoko Koyama, Zhan Gao, Oliver S. Thomas, Marie Follo, Ali Al-Ahmad, Gabriele Prinz, Sandra Duquesne, Heide Dierbach, Susanne Kirschnek, Tim Lämmermann, Martin J. Blaser, Brian T. Fife, Bruce R. Blazar, Andreas Beilhack, Geoffrey R. Hill, Georg Häcker, Robert Zeiser
Neutrophils provide cellular communication between ileum and mesenteric lymph nodes at graft-versus-host disease onset
published pages: 1858-1869, ISSN: 0006-4971, DOI: 10.1182/blood-2017-10-812891 		Blood 131/16 2019-06-19
2018 Alessandro Prestipino, Alica J. Emhardt, Konrad Aumann, David O’Sullivan, Sivahari P. Gorantla, Sandra Duquesne, Wolfgang Melchinger, Lukas Braun, Slavica Vuckovic, Melanie Boerries, Hauke Busch, Sebastian Halbach, Sandra Pennisi, Teresa Poggio, Petya Apostolova, Pia Veratti, Michael Hettich, Gabriele Niedermann, Mark Bartholomä, Khalid Shoumariyeh, Jonas S. Jutzi, Julius Wehrle, Christine Dierks, Heiko Becker, Annette Schmitt-Graeff, Marie Follo, Dietmar Pfeifer, Jan Rohr, Sebastian Fuchs, Stephan Ehl, Frederike A. Hartl, Susana Minguet, Cornelius Miething, Florian H. Heidel, Nicolaus Kröger, Ioanna Triviai, Tilman Brummer, Jürgen Finke, Anna L. Illert, Eliana Ruggiero, Chiara Bonini, Justus Duyster, Heike L. Pahl, Steven W. Lane, Geoffrey R. Hill, Bruce R. Blazar, Nikolas von Bubnoff, Erika L. Pearce, Robert Zeiser
Oncogenic JAK2 V617F causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms
published pages: eaam7729, ISSN: 1946-6234, DOI: 10.1126/scitranslmed.aam7729 		Science Translational Medicine 10/429 2019-06-19
2018 Nimitha R Mathew, Francis Baumgartner, Lukas Braun, David O\'Sullivan, Simone Thomas, Miguel Waterhouse, Tony A Müller, Kathrin Hanke, Sanaz Taromi, Petya Apostolova, Anna L Illert, Wolfgang Melchinger, Sandra Duquesne, Annette Schmitt-Graeff, Lena Osswald, Kai-Li Yan, Arnim Weber, Sonia Tugues, Sabine Spath, Dietmar Pfeifer, Marie Follo, Rainer Claus, Michael Lübbert, Christoph Rummelt, Hartmut Bertz, Ralph Wäsch, Johanna Haag, Andrea Schmidts, Michael Schultheiss, Dominik Bettinger, Robert Thimme, Evelyn Ullrich, Yakup Tanriver, Giang Lam Vuong, Renate Arnold, Philipp Hemmati, Dominik Wolf, Markus Ditschkowski, Cordula Jilg, Konrad Wilhelm, Christian Leiber, Sabine Gerull, Jörg Halter, Claudia Lengerke, Thomas Pabst, Thomas Schroeder, Guido Kobbe, Wolf Rösler, Soroush Doostkam, Stephan Meckel, Kathleen Stabla, Stephan K Metzelder, Sebastian Halbach, Tilman Brummer, Zehan Hu, Joern Dengjel, Björn Hackanson, Christoph Schmid, Udo Holtick, Christof Scheid, Alexandros Spyridonidis, Friedrich Stölzel, Rainer Ordemann, Lutz P Müller, Flore Sicre-de-Fontbrune, Gabriele Ihorst, Jürgen Kuball, Jan E Ehlert, Daniel Feger, Eva-Maria Wagner, Jean-Yves Cahn, Jacqueline Schnell, Florian Kuchenbauer, Donald Bunjes, Ronjon Chakraverty, Simon Richardson, Saar Gill, Nicolaus Kröger, Francis Ayuk, Luca Vago, Fabio Ciceri, Antonia M Müller, Takeshi Kondo, Takanori Teshima, Susan Klaeger, Bernhard Kuster, Dennis (Dong Hwan) Kim, Daniel Weisdorf, Walter van der Velden, Daniela Dörfel, Wolfgang Bethge, Inken Hilgendorf, Andreas Hochhaus, Geoffroy Andrieux, Melanie Börries, Hauke Busch, John Magenau, Pavan Reddy, Myriam Labopin, Joseph H Antin, Andrea S Henden, Geoffrey R Hill, Glen A Kennedy, Merav Bar, Anita Sarma, Donal McLornan, Ghulam Mufti, Betul Oran, Katayoun Rezvani, Omid Shah, Robert S Negrin, Arnon Nagler, Marco Prinz, Andreas Burchert, Andreas Neubauer, Dietrich Beelen, Andreas Mackensen, Nikolas von Bubnoff, Wolfgang Herr, Burkhard Becher, Gerard Socié, Michael A Caligiuri, Eliana Ruggiero, Chiara Bonini, Georg Häcker, Justus Duyster, Jürgen Finke, Erika Pearce, Bruce R Blazar, Robert Zeiser
Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells
published pages: 282-291, ISSN: 1078-8956, DOI: 10.1038/nm.4484 		Nature Medicine 24/3 2019-06-19
2016 A. Schonle, F. A. Hartl, J. Mentzel, T. Noltner, K. S. Rauch, A. Prestipino, S. A. Wohlfeil, P. Apostolova, A.-K. Hechinger, W. Melchinger, K. Fehrenbach, M. C. Guadamillas, M. Follo, G. Prinz, A.-K. Ruess, D. Pfeifer, M. Angel del Pozo, A. Schmitt-Graeff, J. Duyster, K. I. Hippen, B. R. Blazar, K. Schachtrup, S. Minguet, R. Zeiser
Caveolin-1 regulates TCR signal strength and regulatory T-cell differentiation into alloreactive T cells
published pages: 1930-1939, ISSN: 0006-4971, DOI: 10.1182/blood-2015-09-672428 		Blood 127/15 2019-06-19
2017 Hana Andrlová, Justin Mastroianni, Josef Madl, Johannes S. Kern, Wolfgang Melchinger, Heide Dierbach, Florian Wernet, Marie Follo, Kristin Technau-Hafsi, Cristina Has, Venugopal Rao Mittapalli, Marco Idzko, Ricarda Herr, Tilman Brummer, Hendrik Ungefroren, Hauke Busch, Melanie Boerries, Andreas Narr, Gabriele Ihorst, Claire Vennin, Annette Schmitt-Graeff, Susana Minguet, Paul Timpson, Justus Duyster, Frank Meiss, Winfried Römer, Robert Zeiser
\"Biglycan expression in the melanoma microenvironment promotes invasiveness via increased tissue stiffness inducing integrin-β1 expression\"
published pages: , ISSN: 1949-2553, DOI: 10.18632/oncotarget.17160 		Oncotarget 2019-06-19

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