Prof. Dr. Robert Zeiser

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:

• Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease.
  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 (2021).
  N Engl J Med. 385(3):228-238.
• Oncogenic KrasG12D causes myeloproliferation via NLRP3 inflammasome activation.
  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 (2020).
  Nat Commun. 11(1):1659.
• Metabolic reprogramming of donor T cells enhances graft-versus-leukemia effects in mice and humans.
  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 (2020).
  Sci Transl Med. 12(567):eabb8969.
• Graft-versus-host disease of the CNS is mediated by TNF upregulation in microglia.
  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 (2020).
  J Clin Invest. 130:1315-29
• Extracorporeal photopheresis for severe immune checkpoint inhibitor-induced autoimmune colitis.
  Apostolova P, Unger S, Meiss F, von Bubnoff D, Aumann K, Becher B, Zeiser R (2019).
  The New England Journal of Medicine 382: 294-6, 2020
• Immunization against poly-N-acetylglucosamine reduces neutrophil activation and GVHD while sparing microbial diversity.
  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 (2019).
  Proc Natl Acad Sci U S A. 116(41):20700-20706
• 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
• 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.
• 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