Cluster of Excellence –
University of Freiburg

Prof. Dr. Robert Zeiser

Prof. Dr. Robert Zeiser

Hematology and Oncology
University Medical Center Freiburg

+49 761 270 36250

 

The work of my group is focussed on mechanisms that regulate immune responses after allogeneic hematopoietic cell transplantation (allo-HCT). The clinical-translational aspect is that acute graft-versus-host disease is a major barrier for a broader application of allo-HCT in patients with cancer. My group has investigated the role of mTOR signalling for regulatory and conventional T cell function in vivo and described that STAT5 activation is critically involved in regulatory T cell development and maintenance following allo-HCT. Furthermore, we study the role of different GTPases in the process of alloantigen driven T cell responses. We observed that the T cell phenotype and cytokine production is dependent on L-mevalonate metabolites including farnesyl- and geranylgeranylpyrophosphates which mediate attachment of GTPases to the cell membrane. Recently we investigated the role of extracellular ATP as a danger signal activating antigen presenting cells following allo-HCT. Molecular imaging is employed to assess trafficking, survival and proliferation of different immune and cancer cells in vivo.

 

10 selected publications:

  • Oncogenic JAK2V617F causes PD-L1 expression mediating immune-escape in myeloproliferative neoplasms.
    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 (2018). Sci Transl Med. 10 (429)
  • Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD mutant leukemia cells.
    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 (2018).
    Nat Medicine 24: 282-291
  • Neutrophils provide cellular communication between ileum and mesenteric lymph nodes at graft-versus-host disease onset.
    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 (2018).
    Blood. 131:1858-1869
  • Acute Graft-versus-Host Disease - Advances in Biology, Prevention and Therapy.
    Zeiser R, Blazar B (2017).
    N Engl J Med. 377(22):2167-2179
  • Chronic graft-versus-host disease Diagnosis, Prognosis and Novel therapeutic targets.
    Zeiser R, Blazar BR (2017).
    N Engl J Med. 377(26):2565-2579
  • Neutrophil granulocytes recruited upon translocation of intestinal bacteria enhance graft-versus-host disease via tissue damage.
    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 GC, Häcker G, Zeiser R (2014).
    Nat Med. 20(6):648-54.
  • BRAF inhibitor-associated ERK activation drives development of chronic lymphocytic leukemia.
    Yaktapour N, Meiss F, Mastroianni J, Zenz T, Andrlova H, Mathew NR, Claus R, Hutter B, Frohling S, Brors B, Pfeifer D, Pantic M, Bartsch I, Spehl TS, Meyer PT, *Duyster J, *Zirlik K, *Brummer T, *Zeiser R (2014).
    J Clin Invest 124, 5074-5084
  • MiR-146a regulates the TRAF6/TNF-axis in donor T cells during GVHD.
    Stickel N, Prinz G, Pfeifer D, Hasselblatt P, Schmitt-Graeff A, Follo M, Thimme R, Finke J, Duyster J, Salzer U, Zeiser R (2014).
    Blood 124, 2586-2595
  • The Nlrp3 inflammasome regulates acute graft-versus-host disease.
    Jankovic D, Ganesan J, Bscheider M, Stickel N, Weber FC, Guarda G, Follo M, Pfeifer D, Tardivel A, Ludigs K, Bouazzaoui A, Kerl K, Fischer JC, Haas T, Schmitt-Gräff A, Manoharan A, Müller L, Finke J, Martin SF, Gorka O, Peschel C, Ruland J, Idzko M, Duyster J, Holler E, French LE, *Poeck H, *Contassot E, *Zeiser R (2013).
    J Exp Med 210, 1899-1910
  • Graft-versus-host disease is enhanced by extracellular ATP activating P2X(7)R.
    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 (2010).
    Nature Medicine 12, 1434-1438
    *contributed equally