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Klinik für Innere Medizin IHämatologie, Onkologie und Stammzelltransplantation

Allo-Immunregulation

Dr. Alabbas Alkhatib

Dr. Alabbas Alkhatib
Postdoc

alabbas.alkhatib@uniklinik-freiburg.de

Dr. med. Hana Andrlova

Dr. med. Hana Andrlova
Ärztin

hana.andrlova@uniklinik-freiburg.de

Dr. Sophia Chen

Dr. Sophia Chen
Postdoc

sophia.chen@uniklinik-freiburg.de

Heide Dierbach

Heide Dierbach
Techn. Assistentin Med.

heide.dierbach@uniklinik-freiburg.de

Sandra Duquesne

Sandra Duquesne
Med. Techn. Assistentin

sandra.duquesne@uniklinik-freiburg.de

Shaima'a Hamarsheh

Shaima'a Hamarsheh
PhD Student

shaimaa.hamarsheh@uniklinik-freiburg.de

Kathrin Hanke

Kathrin Hanke
Biologische Doktorandin

kathrin.hanke@uniklinik-freiburg.de

Jan Hülsdünker

Jan Hülsdünker
Dipl. Mol Med.

jan.huelsduenker@uniklinik-freiburg.de

Justin Mastroianni

Justin Mastroianni
Biologischer Doktorand

justin.mastroianni@uniklinik-freiburg.de

Dr. Wolfgang Melchinger

Dr. Wolfgang Melchinger
Postdoc

wolfgang.melchinger@uniklinik-freiburg.de

 

 

Dr. Nimitha Rose Mathew

Dr. Nimitha Rose Mathew
Postdoc

nimitha.mathew@uniklinik-freiburg.de

Sarah Niessen

Sarah Niessen
Medizinische Doktorandin

sarah.niessen@uniklinik-freiburg.de

Johana Noroña

Johana Noroña
PhD Student

johana.norona@uniklinik-freiburg.de

Alessandro Prestipino

Alessandro Prestipino
Biologischer Doktorand

alessandro.prestipino@uniklinik-freiburg.de

Dr. Natalie Stickel

Dr. Natalie Stickel
Postdoc

natalie.stickel@uniklinik-freiburg.de

Dr. Sanaz Taromi

Dr. Sanaz Taromi
Postdoc

sanaz.taromi@uniklinik-freiburg.de

Franziska Uhl

Franziska Uhl
Dipl. Biol.
Biologische Doktorandin

franziska.uhl@uniklinik-freiburg.de

Janaki Manoja Vinnakota

Janaki Manoja Vinnakota
PhD student

janaki.vinnakota@uniklinik-freiburg.de

Florian Wernet

Florian Wernet
Technischer Assistent

florian.wernet@uniklinik-freiburg.de

Kai-Li Yan

Kai-Li Yan
Medizinische Doktorandin

kai-li.yan@uniklinik-freiburg.de

  • Christoph Dürr
  • Konrad Wilhelm
  • Laura Debatin
  • Anne Schönle
  • Kristina Maas
  • Jayanthi Ganesan
  • Lukas Schwab
  • Stefan Haug
  • Joseena Iype
  • Franziska Leonhardt
  • Anne-Kathrin Hechinger
  • Vera von Kap-Herr
  • Verena Klämbt
  • Yvonne Beck
  • Luise Goroncy
  • Vincent Schwarze
  • Anne Schönle
  • Sebastian Wohlfeil
  • Francis Baumgartner
  • Sophia Chen
  • Elisabeth Lieberknecht
  • Benjamin Smith
  • Natalie Stickel
  • Lukas Braun
  • Oliver Thomas
  • Stephanie Eckerle
  • Alica Emhardt
  • Theresa Nöltner
  • Lena Oßwald
  • Die Rolle von "Danger associated molecular patterns" bei Graft-versus-host Erkrankung
  • Purinerge Rezeptoren und Adenosinphosphat Metabolismus bei GvHD
  • Migration und Funktion von Zellpopulationen nach allogener hämatopoetischer Zelltransplantation im Mausmodell
  • Immunrekonstitution nach allogener hämatopoetischer Zelltransplantation
  • Tumorzellmigration im Mausmodell, Tumormicroenvironment, Molekulare Bildgebung

Scientific focus

  • The role of "Danger associated molecular patterns" during Graft-versus-host disease
  • Purinergic receptors and Adenosinphosphate metabolism in GvHD
  • Migration and function of different cell populations following allogeneic hematopoietic cell transplantation
  • Immune reconstitution after allogeneic hematopoietic cell transplantation
  • Tumor cell migration in the mouse model, tumor microenvironment and molecular imaging

The work of my group is focused on mechanisms that regulate immune responses after allogeneic hematopoietic cell transplantation (allo-HCT) in particular graft-versus-host disease, immune reconstitution and anti-tumor immunity. 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. Recently we investigated the role of extracellular ATP as a danger signal activating antigen presenting cells following allo-HCT. Functionally we could show a role for ATP and uric acid acting on the Nlrp3 inflammasome. In these studies molecular imaging was employed to assess trafficking, survival and proliferation of different immune and cancer cells in vivo. My group has investigated the role of the kinases JAK1/2 for GVHD and reported that  activation of these kinases is critically involved in the pathomechanism of GVHD. Based on these studies in the mouse model we have then contributed to a clinical application of pharmacological JAK1/2 inhibition leading to significant response rates in patients with GvHD that had failed multiple previous therapies.

  • Prof. Erika Pearce, MPI Freiburg
  • Prof. Bruce Blazar, Univ. of Minnesota, USA
  • Prof. Geoff Hill, Univ. of Brisbane, Australia
  • Prof. Dr. A. Schmitt-Gräff (Pathologisches Institut, Universitätsklinikum Freiburg)
  • Prof. Dr. P. Fisch (Pathologisches Institut, Universitätsklinikum Freiburg)
  • Prof. Dr. S. Laßmann, Prof. Werner, Abteilung Pathologie, Universitätsklinik Freiburg
  • Dr. W. Reichardt, Prof. J. Hennig, Radiologische Klinik, Sektion Bildgebende und Funktionelle Medizinische Physik, Universitätsklinik Freiburg
  • Prof. G. Häcker, Medizinische Mikrobiologie und Hygiene, Universitätsklinik Freiburg
  • Prof. M. Prinz, Abteilung für Neuropathologie, Universitätsklinik Freiburg
  • Prof. P. Henneke, CCI und Zentrum für Kinderheilkunde und Jugendmedizin, Freiburg
  • Prof. Dr. D. Wolf, Abteilung für Hämatologie und Onkologie, Universitätsklinikum Bonn
  • Prof. E. Ullrich, Universitätsklinikum Frankfurt
  • Prof. A. Beilhack, Abteilung Hämatologie und Onkologie, Universität Würzburg
  • Prof. T. Brummer, Institut für Molekulare Medizin und Zellforschung, Freiburg
  • Dr. Petya Apostolova, Klinik für Innere Medizin I, Universitätsklinikum Freiburg
  • Prof. W. Schamel, Biologie, Freiburg
  • Prof. Dr. L. Thompson, Department of Microbiology und Immunology, University of Oklahoma Health Sciences Center, Oklahoma, USA
  • Prof. G. Hildebrandt, University of Kentucky, USA
  1. 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  
  2. 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  doi: 10.1038/nm.4484. 2018 
  3. 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 Feb 20. doi: 10.1182/blood-2017-10-812891.
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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
  21. 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

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