GvHDCure SIGNED
Understanding the dynamics of the immune system to cure graft-versus-host disease (GvHD).
Total Cost €
0EC-Contrib. €
0Partnership
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Project "GvHDCure" data sheet
The following table provides information about the project.
| Coordinator |
UNIVERSITAETSKLINIKUM FREIBURG
Organization address contact info |
| 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.
| # | ||||
|---|---|---|---|---|
| 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 |
|---|---|---|---|
| 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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