Zu den Inhalten springen

Klinik für Innere Medizin IHämatologie, Onkologie und Stammzelltransplantation

Zeiser Lab


Scientific focus

The work of my group is focused on mechanisms that regulate immune responses against tumor cells, with a particular focus on leukemia and melanoma. Immunotherapeutic measures that we apply include mainly  allogeneic hematopoietic cell transplantation (allo-HCT) and immune checkpoint blocker (ICB)-based therapy.

We aim to improve the anti-tumor immune response in these settings by combination therapies that are often based on a link between oncogenic signaling and immune escape, e.g. kinase inhibition and T cell transfer for FLT3-ITD AML (Mathew N et al. Nat Med 2018), ICB for JAK2 mutant MPN (Prestipino A et al. Sci Trans Med 2018), ICB and miR146a antagomir for melanoma (Mastroianni J et al. Cancer Res. 2019), IL-1β / NLRP3 inhibition for KRAS-G12D driven leukemia (Hamarsheh S et al. Nat Comm. 2020) and allo-HCT and lactic acid neutralization for AML (Uhl F et al. Sci Trans Med 2020).

These immunotherapeutic interventions cause immune mediated side effects which include acute graft-versus-host disease (GVHD) after allo-HCT and immune related adverse events (irAEs) after ICB therapy. We could show a role for ATP and uric acid acting on the Nlrp3 inflammasome in GVHD (Wilhelm et al. Nat Med 2010, Jankovic JEM 2013). For irAEs we found that extracorporal photopheresis was effective (Apostolova et al. NEJM 2020). We found in mice that JAK1/2 inhibition reduces GVHD which led to a positive phase-III trial (Zeiser et al. NEJM 2020) and the FDA approval of the JAK1/2 inhibitor ruxolitinib for acute GVHD. We observed in mice and patients that JAK1/2 inhibition reduces chronic GVHD (Zeiser R et al. Leukemia 2015) which was the basis for a phase-III trial showing a superior response rate and failure free survival of cGVHD patients treated with ruxolitinib compared best available therapy (Zeiser et al. NEJM 2021).

Key words: Tumor immunology, oncogenic signaling, allogeneic hematopoietic cell transplantation (allo-HCT), Graft-versus-host disease (GVHD), Anti-leukemia immune responses, immune checkpoint blockade therapy (ICB), immune related adverse events (irAEs).



Dimitrios Athanassopoulos
Medizinischer Doktorand

Nana Talvard-Balland

Francesca Biavasco

Lukas Braun

Lukas Braun
PhD Student Molekulare Medizin

Sangya Chatterjee
PhD student

Marie Czech

Marie Czech
PhD Student

Sandra Duquesne

Sandra Duquesne
Med. Techn. Assistentin

Victor Fetsch
PhD Student

Enrique De Vegas Gomez

Eileen Haring

Eileen Haring
PhD Student Biologie

Alicia Heitzler

Alicia Heitzler
Wissenschaftliche Hilfskraft

Jenny Ho

Jenny Ho
Medizinische Doktorandin

Rebeka Javorniczky

Dr. med. univ. Rebeka Javorniczky

Dr. Natalie Köhler

Dr. Natalie Köhler (geb. Stickel)

Marlene Langenbach

Marlene Langenbach
PhD Student Biologie

Dr. Wolfgang Melchinger

Dr. Wolfgang Melchinger

Stefan Richtsfeld

Stefan Richtsfeld
Medizinischer Doktorand

Jeongmin Ryoo

Jeongmin Ryoo, Ph.D

Dominik Schmidt

Dominik Schmidt
PhD Student Molekulare Medizin

Taromi Sanaz

Dr. Sanaz Taromi

Janaki Manoja Vinnakota

Janaki Manoja Vinnakota
PhD student

  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 consolidator grant
  • 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)

  • 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. 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. 2021 Aug 15;520:385-399. 

  2. 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.

  3. 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. 

  4. 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.

  5. 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                      
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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.
  12. 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  
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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
  21. 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
  22. 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
  23. 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
  24. 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
  25. 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
  26. 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
  27. 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
  28. 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
  29. 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
  30. 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
  31. 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
  32. 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
  33. 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.
  34. 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.
  35. 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.
  36. 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.
  37. 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. (cited > 450 times)
  38. 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.

Deutscher Krebspreis (DKG)

Science Award of the Berlin Brandenburgische Akademie der Wissenschaften

Paul-Martini-Preis 2019

Richtzenhain-Preis 2016 (Deutsche Krebsforschungszentrum, DKFZ)

ERC Consolidator grant (European Research Council)

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

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

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

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

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

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

Elected Heisenberg Fellow (German Research Foundation, DFG)

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

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

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

Trainee Research Award, American Society of Hematology

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)