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Zeiser Lab

Allo-Immunregulation

Scientific focus

Our work can be divided into two major themes that are connected:

Cancer immune escape mechanisms and Cancer immunotherapy induced side effects

 

Focus 1: Cancer immune escape mechanisms

Our goal is to develop rational combinatorial treatments, which target oncogenic signalling and activate immune cells to interfere with cancer cell immune evasion. We could previously show connections between oncogenic proteins or reduced expression of tumor suppressors and immune evasion. Our preclinical studies have led to novel therapeutic concepts and corresponding clinical trials.

 

Preclinical studies:

FLT3-inhibition (sorafenib) induces IL-15 in FLT3-ITD AML cells (Nat Med 2018)

JAK2-V617F induces PD-L1 expression in MPN (Science Trans Med 2018)

BRAF/miR146a reduce IFNү production in melanoma (Cancer Res. 2019)

KRAS-G12D induces NLRP3/IL1ß activation in AML (Nat Comm 2020)

AML derived lactic acid reprograms T cells (Science Trans Med 2020)

Demethylating therapy enhances CAR T cell activity against AML (Nat Comm 2020)

Enhanced p53 expression causes MHC-II upregulation in leukemia (Blood 2022)

MDM2 blockade induces IL-15 production by melanoma cells (Mol Cancer Res 2023)

FLT3-ITD induces immunosuppressive TIM3 ligands in AML (ASH 2023)

 

Corresponding clinical trials (published or ongoing):

Sorafenib reduces the relapse risk of FLT3-ITD AML after allo-HCT (JCO 2020)

PD-1 inhibition plus Aza for AML (Brit J Haematol 2023)

NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy (Cell Rep Med. 2023)

MDM2 inhibition (siremadlin) to prevent AML relapse (Clinical Trial NCT05447663)

TIM3-inhibition (sabatolimab) for AML post allo-HCT (Clinical Trial NCT04623216, ASH 2023)

 

 

Focus 2: Cancer immunotherapy mediated side effects:

Immunotherapeutic interventions cause immune mediated side effects which include acute graft-versus-host disease (GVHD) after allo-HCT, Immune effector cell-associated neurotoxicity syndrome (ICANS) after CAR T cell transfer and immune related adverse events (irAEs) after immune checkpoint inhibition.

 

Preclinical studies:

GVHD:

ATP promotes acute GVHD (Nat Med 2010)

Uric acid enhances acute GVHD (JEM 2013)

Neutrophils cause tissue daamage during acute GVHD (Nat Med 2014)

Ruxolitinib (JAK1/2 inhibition) reduces acute GVHD (Blood 2014)

Ruxolitinib reduces chronic GVHD (Leukemia 2015)

GLP-2 causes intestinal regeneration during aGVHD (Blood 2020)

ROCK1/2-inhibition reduces aGVHD (Nat Comm 2024)

Lipocalin-2 defines a regulatory neutrophil subset during aGVHD (in press)

 

ICANS:  

TAK-1 inhibition for ICANS, CAR Tc causing microglia activation (ASH 2023)

 

irAEs:

Extracorporal photopheresis (ECP) for ICI-colitis (NEJM 2020)

 

 

Corresponding clinical trials (published or ongoing):

GVHD:

REACH2 phase-III trial; leading to EMA approval of the JAK1/2 inhibitor ruxolitinib for SR/D-acute GVHD (NEJM 2020)

REACH3 phase-III trial; leading to FDA and EMA approval of ruxolitinib for SR/D-chronic GVHD (NEJM 2021)

GLP2 (apraglutide) for intestinal acute GVHD, phase I/IIb trial (NCT05415410)

IDUNN trial, MSC vs BAT for SR acute GVHD, phase III trial (NCT04629833)

 

irAEs:

Extracorporal photopheresis (ECP) for ICI-colitis, phase I/IIb trial (EudraCT Number: 2021-002073-26)

 

Team

Principal Investigator

Prof. Dr. Robert Zeiser

robert.zeiser@uniklinik-freiburg.de

 

Nana Talvard-Balland
Postdoc

nana.talvard-balland@uniklinik-freiburg.de

Francesca Biavasco
Postdoc

francesca.biavasco@uniklinik-freiburg.de

Lukas Braun

Lukas Braun
PhD Student Molekulare Medizin

lukas.braun@uniklinik-freiburg.de

Ann-Cathrin Burk
PhD Studentin

 ann-cathrin.burk@uniklinik-freiburg.de

Sangya Chatterjee
PhD student

sangya.chatterjee@uniklinik-freiburg.de

Marie Czech

Marie Czech
PhD Student

marie.czech@uniklinik-freiburg.de

Sandra Duquesne

Sandra Duquesne
Med. Techn. Assistentin

sandra.duquesne@uniklinik-freiburg.de

Cornelia Endres
Masterstudentin

cornelia.endres@uniklinik-freiburg.de

Viktor Fetsch
PhD Student

viktor.fetsch@uniklinik-freiburg.de

Jana Gawron
PhD Studentin

 jana.gawron@uniklinik-freiburg.de

Dr. Natalie Köhler

Dr. Natalie Köhler (geb. Stickel)
Juniorprofessorin

natalie.koehler@uniklinik-freiburg.de

Verena Holzmüller
PhD student

verena.holzmueller@uniklinik-freiburg.de

Dr. Kristina Maas-Bauer
Ärztin, Juniorgruppenleiterin

kristina.maas-bauer@uniklinik-freiburg.de

Marzieh Hesam Mohammadi
PhD Student

marzieh.mohammadi@uniklinik-freiburg.de

Ines Morgado de Sa
PhD Student

ines.morgado.sa@uniklinik-freiburg.de

Dr. Wolfgang Melchinger

Dr. Wolfgang Melchinger
Postdoc

wolfgang.melchinger@uniklinik-freiburg.de

Dominik Schmidt

Dominik Schmidt
PhD Student Molekulare Medizin

dominik.schmidt@uniklinik-freiburg.de

Rachana Srinivasa
PhD student

rachana.srinivasa@uniklinik-freiburg.de

Lennard_Schwöbel
med. Doktorand

 lennard.schwoebel@uniklinik-freiburg.de

 

Janaki Manoja Vinnakota
Post-doctoral researcher

janaki.vinnakota@uniklinik-freiburg.de

Valentin Wenger
Medizinischer Doktorand

valentin.wenger@uniklinik-freiburg.de

Alexander Zähringer
med. Doktorand

alexander.zaehringer@uniklinik-freiburg.de

2023 | Frau Dr. Jenny Ho hat am 18.10.2023 den Karl Joseph Beck Preis 2023 für Ihre Promotionsarbeit zur Rolle von p53/MDM2 in der Immunantwort gegen Leukämiezellen (AG Zeiser) erhalten.

2023 | ERC Advanced Grant für Robert Zeiser

Frau Syngia Chatterjee (AG Zeiser) hat den Young scientist Poster award (EMBO award) bei dem INTERNATIONAL SYMPOSIUM on Brain Myeloid Cells gewonnen.

Our work in Blood (Ho et al. Blood 140, 1167-1181, 2022) was highlighted by this Editorial:

Bleakley M, Biernacki M.

MDM2 inhibition augments GVL effect.

Blood. 2022 Sep 8;140(10):1064-1065.

Our work in Lancet Haematology (Zeiser R. et al. Lancet Haematol 2022 Jan;9(1):e14-e25. doi: 10.1016/S2352-3026(21)00367-7) was highlighted by this Editorial:
Paczesny S. Graft-versus-host disease treatment beyond corticosteroids in newly diagnosed patients?
Lancet Haematol. 2022 Jan;9(1):e2-e3. doi: 10.1016/S2352-3026(21)00376-8. PMID: 34971578.


Prof. Dr. Robert Zeiser has received the CIBSS publication award by the Centre for Integrative Biological Signaling Studies.


  1. Our work by Norona J et al. Blood 2020 was highlighted on the Cover page of Blood
     
  2. Our work in the NEJM paper was highlighted by this Editorial: Cao et al. N Engl J Med 2020; 382:1853-1854
     
  3. Our work by Hülsdünker was highlighted by an Editorial: Martin PJ. Blood. 2018 Apr 19;131(16):1774-1775

  • ERC Advanced
  • SFB1160 (Teilprojekt)
  • TRR/SFB 167 (Teilprojekt)
  • SFB850 (Teilprojekt, Service Projekt)
  • DFG individual grant
  • Heisenberg Professorship (until 2019)
  • Deutsche José Carreras Leukämie-Stiftung
  • Deutsche Krebshilfe
  • Wilhelm Sander-Stiftung
  • SFB1479 (Speaker)
  • BMBF

  • Erika Pearce (MPI Freiburg / Baltimore)
  • Takanori Teshima (Hokkaiko, Japan)
  • Geoffrey Hill (Fred Hutchinson Cancer Research Centre, Seattle)
  • Bruce Blazar (University of Minnesota)
  • Pavan Bachyreddy (DFCI, Boston)
  • Luca Vago (University of Milano)
  • Gerald Pier (Brigham and Women's Hospital/Harvard Medical School, Boston)
  • Robert Negrin (Stanford University)
  • Gerard Socié (Univ. of Paris)
  • Mathew Cooper (Univ. of Queensland, Brisbane)
  • Dean Felsher (Stanford University)
  • Georg Häcker (Microbiology, Freiburg)
  • Marco Prinz (Neuropathology, Freiburg)
  • Andreas Beilhack (Hematology/Oncology, Würzburg)
  • Tilman Brummer (IMMZ, Freiburg)
  • Tim Lämmermann (MPI Freiburg)
  • Melanie Börries (Medical informatics, Freiburg)
  • Linda Thompson (University of Oklahoma Health Sciences Center, Oklahoma)
  • Olaf Groß (Neuropathology, Freiburg)
  • Miriam Erlacher (Pediatrics, Freiburg)
  • Bertram Bengsch (Med II, Freiburg)
  • Ernst Holler (Hematology/Oncology, Regensburg)
  • Susana Minguet (Biology/BIOSS, Freiburg)
  • Toni Cathomen (Transfusion and Gene Therapy, Freiburg)
  • Francis Ayuk (Univ. Hospital KMT, Hamburg)
  • Ian Frew (Hematology/Oncology, Freiburg)
  • Lena Illert (Hematology/Oncology, Freiburg)
  • Justus Duyster (Hematology/Oncology, Freiburg)
  • Oliver Schilling (Pathology, Freiburg)
  • Mathias Heikenwälder (DKFZ Heidelberg)

1. Czech M*, Schneider S*, Peltokangas N*, El Khawanky N, Ghimire S, Andrieux G, Hülsdünker J, Krausz M, Proietti M, Braun LM, Rückert T, Langenbach M, Schmidt D, Martin I, Wenger V, de Vega E, Haring E, Pourjam M, Pfeifer D, Schmitt-Graeff A, Grimbacher B, Aumann K, Kircher B, Tilg H, Raffatellu M, Thiele Orberg E, Häcker G, Duyster J, Köhler N, Holler E, Nachbaur D, Boerries M, Gerner RR*, Grün D*, Zeiser R*. Lipocalin-2 expression identifies an intestinal regulatory neutrophil population during acute graft-versus-host disease. Science Transl Med. 2024 Feb 21;16(735):eadi1501. doi: 10.1126/scitranslmed.adi1501. 

2. Maas-Bauer K, Stell AV, Yan KL, de Vega E, Vinnakota JM, Unger S, Núñez N, Norona J, Talvard-Balland N, Koßmann S, Schwan C, Miething C, Martens US, Shoumariyeh K, Nestor RP, Duquesne S, Hanke K, Rackiewicz M, Hu Z, El Khawanky N, Taromi S, Andrlova H, Faraidun H, Walter S, Pfeifer D, Follo M, Waldschmidt J, Melchinger W, Rassner M, Wehr C, Schmitt-Graeff A, Halbach S, Liao J, Häcker G, Brummer T, Dengjel J, Andrieux G, Grosse R, Tugues S, Blazar BR, Becher B, Boerries M, Zeiser R. ROCK1/2 signaling contributes to corticosteroid-refractory acute graft-versus-host disease. Nature Commun. 2024 Jan 10;15(1):446.

3. Apostolova P, Kreutmair S, Toffalori C, Punta M, Unger S, Burk AC, Wehr C, Maas-Bauer K, Melchinger W, Haring E, Hoefflin R, Shoumariyeh K, Hupfer V, Lauer EM, Duquesne S, Lowinus T, Gonzalo Núñez N, Alberti C, da Costa Pereira S, Merten CH, Power L, Weiss M, Böke C, Pfeifer D, Marks R, Bertz H, Wäsch R, Ihorst G, Gentner B, Duyster J, Boerries M, Andrieux G, Finke J, Becher B, Vago L, Zeiser R.
Phase II trial of hypomethylating agent combined with nivolumab for acute myeloid leukaemia relapse after allogeneic haematopoietic cell transplantation-Immune signature correlates with response.
Br J Haematol. 2023 Aug 4. doi: 10.1111/bjh.19007. 

4. Langenbach M, Giesler S, Richtsfeld S, da Costa-Pereira S, Rindlisbacher L, Wertheimer T, Braun LM, Andrieux G, Duquesne S, Pfeifer D, Woessner NM, Menssen HD, Taromi S, Duyster J, Boerries M, Brummer T, Blazar BR, Minguet S, Turko P, Levesque MP, Becher B, Zeiser R. MDM2 inhibition enhances immune checkpoint inhibitor efficacy by increasing IL-15 and MHC class II production.
Mol Cancer Res. 2023 Apr 18:MCR-22-0898. doi: 10.1158/1541-7786.MCR-22-0898.

5. Socie G, Niederwieser D, von Bubnoff N, Mohty M, Szer J, Or R, Garrett J, Prahallad AC, Wilke C, Zeiser R.
Prognostic Value of Blood Biomarkers in Steroid-Refractory/Dependent Acute Graft-vs-Host Disease: A REACH2 Analysis.
Blood. 2023 Feb 24:blood.2022018579. doi: 10.1182/blood.2022018579.

6. Ho JNHG, Schmidt D, Lowinus T, Ryoo J, Dopfer EP, Gonzalo Núñez N, Costa-Pereira S, Toffalori C, Punta M, Fetsch V, Wertheimer T, Rittmann MC, Braun LM, Follo M, Briere C, Vinnakota JM, Langenbach M, Koppers F, Shoumariyeh K, Engel H, Rückert T, Märklin M, Holzmayer S, Illert AL, Magon F, Andrieux G, Duquesne S, Pfeifer D, Staniek J, Rizzi M, Miething C, Köhler N, Duyster J, Menssen HD, Boerries M, Buescher JM, Cabezas-Wallscheid N, Blazar BR, Apostolova P, Vago L, Pearce EL, Becher B, Zeiser R.
Targeting MDM2 enhances anti-leukemia immunity after allogeneic transplantation via MHC-II and TRAIL-R1/2 upregulation.
Blood 140, 1167-1181 (2022).

7. Biavasco F, Ihorst G, Wäsch R, Wehr C, Bertz H, Finke J, Zeiser R. Therapy response of glucocorticoid-refractory acute GVHD of the lower intestinal tract.
Bone Marrow Transplant. 2022 Jun 29. doi: 10.1038/s41409-022-01741-3.

8. Zeiser R, Socié G, Schroeder MA, Abhyankar S, Vaz CP, Kwon M, Clausen J, Volodin L, Giebel S, Chacon MJ, Meyers G, Ghosh M, Deeren D, Sanz J, Morariu-Zamfir R, Arbushites M, Lakshminarayanan M, Barbour AM, Chen YB. Efficacy and safety of itacitinib versus placebo in combination with corticosteroids for initial treatment of acute graft-versus-host disease (GRAVITAS-301): a randomised, multicentre, double-blind, phase 3 trial.
Lancet Haematol. 2022 Jan;9(1):e14-e25. doi: 10.1016/S2352-3026(21)00367-7.

9. El Khawanky N, Hughes A, Yu W, Myburgh R, Matschulla T, Taromi S, Aumann K, Clarson J, Vinnakota JM, Shoumariyeh K, Miething C, Lopez AF, Brown MP, Duyster J, Hein L, Manz MG, Hughes TP, White DL, Yong ASM, Zeiser R. Demethylating therapy increases anti-CD123 CAR T cell cytotoxicity against acute myeloid leukemia.
Nat Commun. 2021 Nov 8;12(1):6436.

10. Taromi S, Firat E, Simonis A, Braun LM, Apostolova P, Elze M, Passlick B, Schumacher A, Lagies S, Frey A, Schmitt-Graeff A, Burger M, Schmittlutz K, Follo M, von Elverfeldt D, Zhu X, Kammerer B, Diederichs S, Duyster J, Manz MG, Niedermann G, Zeiser R. Enhanced AC133-specific CAR T cell therapy induces durable remissions in mice with metastatic small cell lung cancer.
Cancer Lett. 2022 Jul 10;538:215697

11. Zeiser R, Polverelli N, Ram R, Hashmi SK, Chakraverty R, Middeke JM, Musso M, Giebel S, Uzay A, Langmuir P, Hollaender N, Gowda M, Stefanelli T, Lee SJ, Teshima T, Locatelli F; REACH3 Investigators. Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease.
The New England Journal of Medicine. 2021 Jul 15;385(3):228-238.

12. Osswald L, Hamarsheh S, Uhl FM, Andrieux G, Klein C, Dierks C, Duquesne S, Braun LM, Schmitt-Graeff A, Duyster J, Boerries M, Brummer T, Zeiser R.
Oncogenic KrasG12D Activation in the Nonhematopoietic Bone Marrow Microenvironment Causes Myelodysplastic Syndrome in Mice.
Mol Cancer Res. 2021 Jun 4. doi: 10.1158/1541-7786.MCR-20-0275. 

13. Uhl FM, Chen S, O'Sullivan D, Edwards-Hicks J, Richter G, Haring E, Andrieux G, Halbach S, Apostolova P, Büscher J, Duquesne S, Melchinger W, Sauer B, Shoumariyeh K, Schmitt-Graeff A, Kreutz M, Lübbert M, Duyster J, Brummer T, Boerries M, Madl T, Blazar BR, Groß O, Pearce EL, Zeiser R.
Metabolic reprogramming of donor T cells enhances graft-versus-leukemia effects in mice and humans.
Science Translational Medicine 2020 Oct 28;12(567):eabb8969.

14. Norona J, Apostolova P, Schmidt D, Ihlemann R, Reischmann N, Taylor G, Köhler N, de Heer J, Heeg S, Andrieux G, Siranosian BA, Schmitt-Graeff A, Pfeifer D, Catalano A, Frew I, Proietti M, Grimbacher B, Bulashevska A, Bhatt AS, Brummer T, Clauditz TS, Zabelina T, Kroeger N, Blazar BR, Boerries M, Ayuk F, Zeiser R.
Glucagon like peptide-2 for Intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans.
Blood. 2020; 136: 1442-1455.
Highlighted in: Chao N. Blood 2020                      

15. Zeiser R, von Bubnoff N, Butler J, Mohty M, Niederwieser D, Or R, Szer J, Wagner EM, Zuckerman T, Mahuzier B, Xu J, Wilke C, Gandhi KK, Socié G, for the REACH2 Trial Group.
Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease.
The New England Journal of Medicine  2020 May 7;382(19):1800-1810
Highlighted in Chao N. Finally, a Successful Randomized Trial for GVHD. N Engl J Med. 2020

16. Hamarsheh S, Osswald L, Saller BS, Unger S, De Feo D, Vinnakota JM, Konantz M, Uhl FM, Becker H, Lübbert M, Shoumariyeh K, Schürch C, Andrieux G, Venhoff N, Schmitt-Graeff A, Duquesne S, Pfeifer D, Cooper MA, Lengerke C, Boerries M, Duyster J, Niemeyer CM, Erlacher M, Blazar BR, Becher B, Groß O, Brummer T, Zeiser R.
Oncogenic KrasG12D causes myeloproliferation via NLRP3 inflammasome activation.
Nature Commun. 2020 Apr 3;11(1):1659.
Highlighted in: Science Daily: Cancer mutation in dual role

17. Apostolova P, Unger S, von Bubnoff D, Meiss F, Becher B, Zeiser R.
Extracorporeal Photopheresis for Colitis Induced by Checkpoint-Inhibitor Therapy.
The New England Journal of Medicine 2020 Jan 16;382(3):294-296

18. R Mathew N, Vinnakota JM, Apostolova P, Erny D, Hamarsheh S, Andrieux G, Kim JS, Hanke K, Goldmann T, Chappell-Maor L, El-Khawanky N, Ihorst G, Schmidt D, Duyster J, Finke J, Blank T, Boerries M, Blazar BR, Jung S, Prinz M, Zeiser R.
Graft-versus-host disease of the CNS is mediated by TNF upregulation in microglia. 
J Clin Invest. 2020 Mar 2;130(3):1315-1329

19. Hülsdünker J, Thomas OS, Haring E, Unger S, Gonzalo Núñez N, Tugues S, Gao Z, Duquesne S, Cywes-Bentley C, Oyardi O, Kirschnek S, Schmitt-Graeff A, Pabst O, Koenecke C, Duyster J, Apostolova P, Blaser MJ, Becher B, Pier GB, Häcker G, Zeiser R.
Immunization against poly-N-acetylglucosamine reduces neutrophil activation and GVHD while sparing microbial diversity.
Proc Natl Acad Sci U S A. 2019 Oct 8;116(41):20700-20706

20. Mastroianni J, Stickel N, Andrlova H, Hanke K, Melchinger W, Duquesne S, Schmidt D, Falk M, Andrieux G, Pfeifer D, Dierbach H, Schmitt-Graeff A, Meiss F, Boerries M, Zeiser R.
miR-146a Controls Immune Response in the Melanoma Microenvironment.
Cancer Res. 2019 Jan 1;79(1):183-195.

21. Prestipino A, Emhardt A, Aumann K, O´Sullivan D, Gorantla SP, Duquesne S, Melchinger W, Braun L, Vuckovic S, Boerries M,  Busch H, Halbach S, Pennisi S, Poggio T, Apostolova P, Veratti P, Hettich M, Niedermann G, Bartholomä M, Shoumariyeh K, Jutzi J, Wehrle J, Dierks C, Becker H, Schmitt-Graeff A, Follo M, Pfeifer D, Rohr J, Fuchs S, Ehl S, Hartl FA, Minguet S, Miething C, Heidel F, Kröger N, Triviai I, Brummer T, Finke J, Illert AL, Ruggiero E, Bonini C, Duyster J, Pahl HL, Lane SW, Hill GR, Blazar BR, Bubnoff N, Pearce EL, Zeiser R.
Oncogenic JAK2V617F causes PD-L1 expression mediating immune-escape in myeloproliferative neoplasms
Science Translational Medicine  10, eaam7729 2018  

22. Mathew NR, Baumgartner F, Braun L, David O´Sullivan, Thomas S, Waterhouse M, Müller TA, Hanke K, Taromi S, Apostolova P, Illert AL, Melchinger W, Duquesne S, Schmitt-Graeff A, Osswald L, Yan K-L., Weber A, Tugues S, Spath S, Pfeifer D, Follo M, Claus R, Lübbert M, Rummelt C, Bertz H, Wäsch R, Haag J, Schmidts A, Schultheiss M, Bettinger M, Thimme R, Ullrich E, Tanriver Y, Vuong GL, Arnold R, Hemmati P, Wolf D, Ditschkowski M, Jilg C, Wilhelm K, Leiber C, Gerull S, Halter J, Lengerke C, Pabst T, Schroeder T, Kobbe G, Rösler W, Doostkam S, Meckel S, Stabla K, Metzelder SK, Halbach S, Brummer T, Hu Z, Dengjel J, Hackanson B, Schmid C, Holtick U, Scheid C, Spyridonidis A, Stölzel F, Ordemann F, Müller LP, Sicre-de-Fontbrune F, Ihorst G, Kuball J, Ehlert JE, Feger D, Wagner EV, Cahn JY, Schnell J, Kuchenbauer F, Bunjes D, Chakraverty R, Richardson S, Gill S, Kröger N, Ayuk F, Vago L, Ciceri F, Müller AM, Kondo T, Teshima T, Klaeger S, Kuster B, Kim D, Weisdorf D, van der Velden W, Dörfel D, Bethge W, Hilgendorf I, Hochhaus A, Andrieux G, Börries M, Busch H, Magenau J, Reddy P, Labopin M, H. Antin J, Henden AS, Hill GR, Kennedy GA, Bar M, Sarma A, McLornan D, Mufti G, Oran B, Rezvani K, Sha O, Negrin RS, Nagler A, Prinz M, Burchert A, Neubauer A, Beelen D, Mackensen A, von Bubnoff N, Herr W, Becher B, Socié G, Caligiuri MA, Ruggiero E, Bonini C, Häcker G, Duyster J, Finke J, Pearce E, Blazar BR, Zeiser R.
Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD mutant leukemia cells.
Nature Medicine  2018 Mar;24(3):282-291

23. Hülsdünker J, Ottmüller KJ, Neeff HP, Koyama M, Gao Z, Thomas OS, Follo M, Al-Ahmad A, Prinz G, Duquesne S, Dierbach H, Kirschnek S, Lämmermann T, Blaser MJ, Fife BT, Blazar BR, Beilhack A, Hill GR, Häcker G, Zeiser R.
Neutrophils provide cellular communication between ileum and mesenteric lymph nodes at graft-versus-host disease onset.
Blood. 2018 Apr 19;131(16):1858-1869.
Highlighted in Martin PJ. Blood. 2018;131(16):1774-1775

24. Zeiser R, Blazar B.  Acute Graft-versus-Host Disease - Advances in Biology, Prevention and Therapy.
The New England Journal of Medicine 377(22):2167-2179, 2017

25. Zeiser R, Blazar BR. Chronic graft-versus-host disease Diagnosis, Prognosis and Novel therapeutic targets.
The New England Journal of Medicine 377(26):2565-2579, 2017

26. Stickel N, Hanke K, Marschner D, Prinz G, Köhler M, Melchinger W, Pfeifer D, Schmitt-Graeff A, Brummer T, Heine A, Brossart P, Wolf D, von Bubnoff N, Finke J, Duyster J, Ferrara J, Salzer U, Zeiser R. MicroRNA-146a reduces MHC-II expression via targeting JAK/STAT signaling in dendritic cells after stem cell transplantation.
Leukemia. 2017 Dec;31(12):2732-2741

27. Andrlová H, Mastroianni J, Madl J, Kern JS, Melchinger W, Dierbach H, Wernet F, Follo M, Technau-Hafsi K, Has C, Mittapalli VR, Idzko M, Herr R, Brummer T, Ungefroren H, Busch H,
Boerries M, Narr A, Ihorst G, Vennin C, Schmitt-Graeff A, Minguet S, Timpson P, Duyster J, Meiss F, Römer W, Zeiser R. Biglycan expression in the melanoma microenvironment promotes invasiveness via increased tissue stiffness inducing integrin-β1 expression.
Oncotarget. Apr 17. doi: 10.18632/oncotarget.17160, 2017

28. Schönle A, Hartl FA, Mentzel J, Nöltner T, Rauch KS, Prestipino A,  Wohlfeil SA, Apostolova P, Hechinger AK, Melchinger W, Fehrenbach K,  Guadamillas MC, Follo M, Prinz G, Ruess AK, Pfeifer D, Del Pozo MA,  Schmitt-Graeff A, Duyster J, Hippen KI, Blazar BR, Schachtrup K,  Minguet S, Zeiser R. Caveolin-1 regulates TCR signal strength and  regulatory T cell differentiation into alloreactive T cells.
Blood 127:1930-9, 2016

29. Klämbt V, Wohlfeil SA, Schwab L, Hülsdünker J, Ayata K, Apostolova P, Schmitt-Graeff A, Dierbach H, Prinz G, Follo M, Prinz M, Idzko M, Zeiser R. A Novel Function for P2Y2 in Myeloid Recipient-Derived Cells during Graft-versus-Host Disease.
J Immunol. 195: 5795-804, 2015

30. Zeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK, Spoerl S, Ditschkowski M, Ecsedi M, Sockel K, Ayuk F, Ajib S, de Fontbrune FS, Na IK, Penter L, Holtick U, Wolf D, Schuler E, Meyer E, Apostolova P, Bertz H, Marks R, Lübbert M, Wäsch R, Scheid C, Stölzel F, Ordemann R, Bug G, Kobbe G, Negrin R, Brune M, Spyridonidis A, Schmitt-Gräff A, van der Velden W, Huls G, Mielke S, Grigoleit GU, Kuball J, Flynn R, Ihorst G, Du J, Blazar BR, Arnold R, Kröger N, Passweg J, Halter J, Socié G, Beelen D, Peschel C, Neubauer A, Finke J, Duyster J, von Bubnoff N. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multi-center survey.
Leukemia 29: 2062-8, 2015

31. Chen S, Smith BA, Iype J, Prestipino A, Pfeifer D, Grundmann S, Schmitt-Graeff A, Idzko M, Beck Y, Prinz G, Finke J, Duyster J, Zeiser R. MicroRNA-155 deficient dendritic cells cause less severe GvHD through reduced migration and defective inflammasome activation.
Blood 126: 103-12, 2015

32. Hechinger AK, Smith BA, Flynn R, Hanke K, McDonald-Hyman C, Taylor PA, Pfeifer D, Hackanson B, Leonhardt F, Prinz G, Dierbach H, Schmitt-Graeff A, Kovarik J, Blazar BR, Zeiser R. Therapeutic activity of multiple common gamma chain cytokine inhibition in acute and chronic GvHD.
Blood 125: 570-80, 2015
Highlighted in Pérez-Simón JA. Blood 125: 424-6. 2015

33. Haug S, Schnerch D, Halbach S, Mastroianni J, Dumit VI, Follo M, Hasenburg A, Köhler M, Dierbach H, Herzog S, Proske A, Werner M, Dengjel J, Brummer T, Laßmann S, Wäsch R, Zeiser R. Metadherin exon 11 skipping variant enhances metastatic spread of ovarian cancer.
Int J Cancer 136: 2328-40, 2015

34. Schwab, L, Goroncy, L, Palaniyandi, S., Gautam, S., Triantafyllopoulou, A., Mocsai, A, Reichardt, W., Karlsson, FJ, Radhakrishnan, SV, Hanke, K, Schmitt-Graeff, A, Freudenberg, M, von Loewenich, FD, Wolf, P, Leonhardt, F, Baxan, N, Pfeifer, D, Schmah, O, Schönle, A, Martin, SF, Mertelsmann, R, Duyster, J, Finke, J., Prinz, M., Henneke, P., Häcker, H., Hildebrandt, G.C, Häcker, G, Zeiser, R. Neutrophil granulocytes recruited upon translocation of intestinal bacteria enhance GvHD via tissue damage.
Nature Medicine 20: 648-54, 2014
Highlighted in Kugelberg E. Nature Reviews Immunology, 2014

35. Yaktapour N, Meiss F, Mastroianni J, Zenz T, Andrlova H, Mathew NR, Claus R, Hutter B, Fröhling S, Brors B, Pfeifer D, Pantic M, Bartsch I, Spehl TS, Meyer PT, Duyster J, Zirlik K, Brummer T, Zeiser R. BRAF inhibitor-associated ERK activation drives development of chronic lymphocytic leukemia.
J Clin Invest. 124: 5074-84, 2014
Highlighted in Wu C.J. J Clin Invest. 124:4681-3, 2014

36. Stickel N, Prinz G, Pfeifer D, Hasselblatt P, Schmitt-Graeff A, Follo M, Thimme R, Finke J, Duyster J, Salzer U, Zeiser R. MiR-146a regulates the TRAF6/TNF-axis in donor T cells during GvHD.
Blood 124: 2586-95, 2014

37. Jankovic D, Ganesan J, Bscheider M, Stickel N, Weber F, Guarda G, Follo M, Pfeifer D, Tardivel A, Ludigs K, Bouazzaoui A, Kerl K, Fischer J, Haas T, Schmitt-Gräff A, Manoharan A, Müller L, Finke J, Martin S, Gorka O, Peschel C, Ruland J, Idzko M, Duyster J, Holler E, French LE, Poeck H*, Contassot E, Zeiser R. The Nlrp3-inflammasome regulates acute graft-versus-host disease.
J Exp Med 210:1899-910, 2013

38. Leonhardt F, Grundmann S, Behe M, Bluhm F, Dumont, RA, Braun F, Melpomeni F, Riesner K, Prinz G, Hechinger AK, Gerlach UV, Dierbach H, Penack O, Schmitt-Gräff A, Finke J, Weber WA, Zeiser R. Inflammatory neovascularization during graft-versus-host disease is regulated by αv integrin and miR-100.
Blood 121:3307-3318, 2013
Highlighted in Komanduri KV et al. Blood 121:3303-4, 2014

39. Leonhardt F. Zirlik K, Buchner M, Prinz G, Hechinger AK, Gerlach UV, Fisch P, Schmitt-Gräff A, Reichardt W, Zeiser R. Spleen tyrosine kinase (Syk) is a potent target for GvHD prevention at different cellular levels.
Leukemia 26: 1617-1629, 2012

40. Wilhelm, K, Ganesan J, Müller T, Dürr C, Grimm, M, Beilhack, A, Krempl, CD, Sorichter, S, Gerlach, UV, Jüttner, E, Zerweck, A, Gärtner, F, Pellegatti, P, Di Virgilio, F, Ferrari, D, Kambham, N, Fisch, P, Finke, J, Idzko, M, Zeiser, R. Graft-versus-host disease is enhanced by extracellular adenosine triphosphate activating P2X7R.
Nature Medicine 12: 1434-1438, 2010

41. Dürr, C, Pfeifer, D, Claus, R, Schmitt-Graeff, A, Gerlach, UV, Graeser, R, Krüger, S, Gerbitz, A, Negrin, RS, Finke, J, Zeiser R. CXCL12 mediates immunosuppression in the lymphoma microenvironment after allogeneic transplantation of hematopoietic cells.
Cancer Research 70: 10170-10181, 2010

42. Zeiser R, Leveson-Gower, D.B., Zambricki, E.A., Kambham, N, Beilhack, A, Loh, J, Hou, J.Z , Negrin RS. Differential impact of mTOR inhibition on CD4+CD25+Foxp3+ regulatory T cells as compared to conventional CD4+ T cells.
Blood 111: 453-462, 2008.

43. Zeiser R, Nguyen VH, Hou JZ, Beilhack A, Zambricki EA, Buess M, Contag CH, Negrin RS. Early CD30 signaling is critical for adoptively transferred CD4+CD25+ regulatory T cells in prevention of acute graft versus host disease.
Blood 109: 2225-2233, 2007.

44. Zeiser R, Youssef, S, Baker J, Kambhan N, Steinman L, Negrin RS. Preemptive HMG-CoA reductase inhibition provides graft-versus-host disease protection by Th-2 polarization while sparing graft-versus-leukemia activity.
Blood 110: 4588-4598, 2007.

45. Zeiser R, Zambricki EA, Leveson-Gower DB, Kambham N, Beilhack A, Negrin RS. Host-Derived Interleukin-18 Differentially Impacts Regulatory and Conventional T Cell Expansion During Acute Graft-versus-Host Disease.
Biology of Blood and Marrow Transplantation 13: 1428-1438, 2007.

46. Zeiser R, Nguyen VH, Beilhack A, Buess M, Schulz S, Baker J, Contag CH, Negrin RS. Inhibition of CD4+CD25+ regulatory T cell function by calcineurin dependent interleukin-2 production.
Blood 108: 390-399, 2006.

47. Zeiser R, Spyridonidis A, Wasch R, Ihorst G, Grullich C, Bertz H, Finke J. Evaluation of immunomodulatory treatment based on conventional and lineage-specific chimerism analysis in patients with myeloid malignancies after myeloablative allogeneic hematopoietic cell transplantation.
Leukemia 19: 814-821, 2005.

2023

ERC Advanced Grant (European Research Council)


2022
Disease prevention award (Deutsche Gesellschaft für Innere Medizin)


2021
Schaefer Award (DAG-HSZT)


2021
CIBSS Award (Cluster of Excellence CIBSS)


2021
Deutscher Krebspreis (Deutsche Krebsgesellschaft)


2020
Science Award of the Berlin Brandenburgische Akademie der Wissenschaften


2019
Paul-Martini-Preis 2019


2017
Richtzenhain-Preis 2016 (Deutsche Krebsforschungszentrum, DKFZ)


2016
ERC Consolidator grant (European Research Council)


2015
Jon J. van Rood Award (European Society for Blood and Marrow Transplantation, EBMT, Istanbul)


2014
Artur Pappenheim Award (German Society of Hematology and Oncology (DGHO) Conference, Hamburg)


2014
Hans Jochem Kolb Award (GvHD/GvL Conference, Regensburg)


2014
Karin Nolte Research Award (SP Internal Medicine Society, Neustadt)


2012
BMT Research Award (German Bone Marrow Transplantation Society, Berlin)


2011
Theodor Frerichs Award (German Society of Internal Medicine, Wiesbaden)


2011
Elected Heisenberg Fellow (German Research Foundation, DFG)


2008
BBMT Editorial Award: Best basic science article of 2007 (ASBMT, San Diego)


2007
Eugen Graetz Research Award, Frbg. University Research Foundation (Freiburg)


2006
ASH Scholar Award of the American Society of Hematology (ASH, Orlando)


2006
Trainee Research Award, American Society of Hematology

Laboratory Activities

Snowshoe hike on Schauinsland

Canoe trip on the Rhine

Lab hike near Hinterzarten

Lab hike along the Mathisleweiher

Our lab members are international...

Animal Imaging Advisory Board

The Animal Imaging Advisory Board is a consulting service for preclinical imaging

The small animal imaging advisory board will help the PIs of the CRC1479 initiative to choose the best imaging method to answer the scientific questions posed by their project. BLI, NMR-spectroscopy, MR hyperpolarisation, ultrasound and CT-based imaging will be provided. Each of this modality has some strengths and weaknesses. Therefore it will be challenging for the individual group leaders to decide which animal imaging modality is the best to answer their specific questions. The animal advisory board should be a forum which supports the project coordinators to define the best approach in respect to their specific requests

The imaging advisory board consists of one project coordinator from each modality.

MRI: Dr. Wilfried Reichardt | wilfried.reichardt@uniklinik-freiburg.de

BLI: Prof. Dr. Robert Zeiser | robert.zeiser@uniklinik-freiburg.de


The PI with interest in animal imaging needs to send the application sheet and a short abstract (about half a side) with the description of the request for an imaging application. The three members review it in a bimonthly meeting and give an advice to the applicant.


Table 1: Complementarity of two representative imaging platforms

Method Advantage
BLI • Fast and low cost method for living animals
• High sensitivity
• Evaluating the kinetics of cell division is possible (signal intensity increases)
• Small cell populations can be detected (as little as 1000 cells in superficial areas)
• The presence of bioluminescence signal indicates that the luc+ cell population is viable
• Luciferase can be used as reporter-probe to monitor promoter activity of a gene of interest
MRI • Highest spatial resolution (< 100 µm )
• Directly translational to human application
• Combines multi contrast 3D morphological with multi modal functional imaging.
(e.g. Diffusion, Flow, fMRI, DCE-MRI and other)
• Passive, active and activatable contrast agents possible

In vivo Bioluminescence Imaging (BLI)

Luciferase-based imaging methods have been recently applied to detect widespread metastasis in different murine tumour models including breast cancer, prostate cancer, ovarian cancer, B cell lymphoma and other entities. BLI is of enormous advantage when small cell populations need to be isolated since it can provide guidance which anatomical regions need to be removed for further analysis. When luc transgenic cells are employed BLI is permissive for cell proliferation analysis since the reporter gene is duplicated upon cell division and thus signal intensity correlates with cell number. Combination of Luc expression and GFP expression in tumor cells allows further purification and analysis of tumor cell by FACS after BLI guided in vivo monitoring and recovery

Sequential bioluminescence imaging displays the metastatic pattern of ovarian cancer cells in immunocompetent mice (data from AG Zeiser).

Nuclear Magnetic Resonance Imaging (MRI)

The ability to generate multiple contrasts non invasively and at high resolution including various functional contrasts has given MRI an important role in clinical diagnostic imaging. These techniques have been translated to dedicated animal systems. Small animal MR is therefore already extensively used in preclinical oncology research, and its impact is growing as in addition to morphology and volumetry numerous processes can be quantitatively imaged. Numerous studies have for example shown the use of MR for measurements of perfusion and permeability by of tissue using DCE-MRI. Diffusion MR has been shown to be effective to control tumor response and to monitor apoptosis. 1H-, 31P- and 13C- spectroscopy has been extensively used to observe tumor metabolism. Currently, rapid progress is being made in the development of molecular probes to observe specific receptors as well as migration of iron oxide or 19F labeled cells. Combined application of parametric measurements has been shown to be a promising tool for therapeutic monitoring and imaging phenotyping of animal models.

Axial MRI images of the abdomen in a nude mouse. Displayed are a diffusion weighted image (left) and a T2-weighted image (right). The detection of a liver metastasis after intra-pancreatic injection of genetically modified tumor cells (data from AG Hennig/Elverfeldt)