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Keller Group

Charité-Universitätsmedizin Berlin
Campus Benjamin Franklin
Hindenburgdamm 30
12203 Berlin

 +49 30 450 513 467

Sie befinden sich hier:

Focus of research

Mechanism-based cancer therapies

Our utmost goal is to identify and target crucial cancer cell vulnerabilities while sparing normal tissue. From discovery approaches to validation and preclinical testing. Aiming for clinical application.

Cancer originates from normal cells through genetic and epigenetic alterations. By employing forward genomic screening we start from a known gene mutation or cancer-associated condition and investigate the path that results in a manifest malignancy. Major further focus areas of the lab include: oncoprotein-induced disturbance of post-translational protein modifications, in particular SUMOylation, and sensing of DNA damage; constitutively activated B-cell receptor and chemokine receptor signaling; and molecular cancer imaging and theranostics.

 

Group Leader

Prof. Dr. med. Ulrich Keller

Director Medical Department, Division of Hematology und Oncology at Campus Benjamin Franklin (CBF)

CBF: Campus Benjamin Franklin

Teamleaders and Principal Investigators

PD Dr. rer. nat. Matthias Wirth

Teamleader and Principal Investigator, Division of Hematology and Oncology at Campus Benjamin Franklin (CBF)

Matthias Wirth is specialized on functional genomics and therapy resistance. The experimental research of his team focuses on
  • Identification of novel therapeutic targets for the development of effective drugs / drug combinations incl. immunotherapeutic approaches to overcome therapy resistance
  • Understanding the ability of tumor cells to evolve and "re-wire" their signaling networks

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Selected publications

Schick M, Zhang L, Maurer S, Maurer HC, Isaakaidis K, Schneider L, Patra U, Schunck K, Rohleder E, Hofstetter J, Baluapuri A, Scherger AK, Slotta-Huspenina J, Hettler F, Weber J, Engleitner T, Maresch R, Slawska J, Lewis R, Istvanffy R, Habringer S, Steiger K, Baiker A, Oostendorp RAJ, Miething C, Lenhof HP, Bassermann F, Chapuy B, Wirth M, Wolf E, Rad R, Müller S, Keller U.: Genetic alterations of the SUMO isopeptidase SENP6 drive lymphomagenesis and genetic instability in diffuse large B-cell lymphoma. Nat Commun. 2022

Demel UM, Böger M, Yousefian S, Grunert C, Zhang L, Hotz PW, Gottschlich A, Köse H, Isaakidis K, Vonficht D, Grünschläger F, Rohleder E, Wagner K, Dönig J, Igl V, Brzezicha B, Baumgartner F, Habringer S, Löber J, Chapuy B, Weidinger C, Kobold S, Haas S, Busse AB, Müller S, Wirth M, Schick M, Keller U.: Activated SUMOylation restricts MHC class I antigen presentation to confer immune evasion in cancer. J Clin Invest. 2022

Doffo J, Bamopoulos SA, Köse H, Orben F, Zang C, Pons M, den Dekker AT, Brouwer RWW, Baluapuri A, Habringer S, Reichert M, Illendula A, Krämer OH, Schick M, Wolf E, van IJcken WFJ, Esposito I, Keller U, Schneider G, Wirth M: NOXA expression drives synthetic lethality to RUNX1 inhibition in pancreatic cancer. Proc Natl Acad Sci U S A. 2022

Biederstädt A, Hassan Z, Schneeweis C, Schick M, Schneider L, Muckenhuber A, Hong Y, Siegers G, Nilsson L, Wirth M, Dantes Z, Steiger K, Schunck K, Langston S, Lenhof HP, Coluccio A, Orben F, Slawska J, Scherger A, Saur D, Müller S, Rad R, Weichert W, Nilsson J, Reichert M, Schneider G, Keller U. SUMO pathway inhibition targets an aggressive pancreatic cancer subtype. Gut. 2020

O'Connor T, Zhou X, Kosla J, Adili A, Garcia Beccaria M, Kotsiliti E, Pfister D, Johlke AL, Sinha A, Sankowski R, Schick M, Lewis R, Dokalis N, Seubert B, Höchst B, Inverso D, Heide D, Zhang W, Weihrich P, Manske K, Wohlleber D, Anton M, Hoellein A, Seleznik G, Bremer J, Bleul S, Augustin HG, Scherer F, Koedel U, Weber A, Protzer U, Förster R, Wirth T, Aguzzi A, Meissner F, Prinz M, Baumann B, Höpken UE, Knolle PA, von Baumgarten L, Keller U, Heikenwalder M. Age-Related Gliosis Promotes Central Nervous System Lymphoma through CCL19-Mediated Tumor Cell Retention. Cancer Cell. 2019

Weber J, de la Rosa J, Grove CS, Schick M, Rad L, Baranov O, Strong A, Pfaus A, Friedrich MJ, Engleitner T, Lersch R, Öllinger R, Grau M, Menendez IG, Martella M, Kohlhofer U, Banerjee R, Turchaninova MA, Scherger A, Hoffman GJ, Hess J, Kuhn LB, Ammon T, Kim J, Schneider G, Unger K, Zimber-Strobl U, Heikenwälder M, Schmidt-Supprian M, Yang F, Saur D, Liu P, Steiger K, Chudakov DM, Lenz G, Quintanilla-Martinez L, Keller U, Vassiliou GS, Cadiñanos J, Bradley A, Rad R. PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice. Nat Commun. 2019

Maurer S, Herhaus P, Lippenmeyer R, Hänscheid H, Kircher M, Schirbel A, Maurer HC, Buck AK, Wester HJ, Einsele H, Grigoleit GU, Keller U, Lapa C. Side effects of CXC-chemokine receptor 4 - directed Endoradiotherapy with Pentixather prior to Hematopoietic Stem Cell Transplantation. J Nucl Med. 2019

Nimmagadda SC, Frey S, Müller P, Wolleschak D, Weinert S, Keller U, Edelmann B, Fischer T. SDF1α-induced chemotaxis of JAK2-V617F positive cells is dependent on Bruton's Tyrosine Kinase and its downstream targets PI3K/AKT, PLCγ1 and RhoA. Haematologica. 2019

Habringer S, Lapa C, Herhaus P, Schottelius M, Istvanffy R, Steiger K, Slotta-Huspenina J, Schirbel A, Hänscheid H, Kircher S, Buck AK, Götze K, Vick B, Jeremias I, Schwaiger M, Peschel C, Oostendorp R, Wester HJ, Grigoleit GU, Keller U. Dual Targeting of Acute Leukemia and Supporting Niche by CXCR4-Directed Theranostics. Theranostics. 2018

Schick M, Habringer S, Nilsson JA, Keller U. Pathogenesis and therapeutic targeting of aberrant MYC expression in haematological cancers. Br J Haematol. 2017

Jespersen H, Lindberg MF, Donia M, Söderberg EMV, Andersen R, Keller U, Ny L, Svane IM, Nilsson LM, Nilsson JA. Clinical responses to adoptive T-cell transfer can be modeled in an autologous immune-humanized mouse model. Nat Commun. 2017

Herhaus P, Habringer S, Philipp-Abbrederis K, Vag T, Gerngross C, Schottelius M, Slotta-Huspenina J, Steiger K, Altmann T, Weißer T, Steidle S, Schick M, Jacobs L, Slawska J, Müller-Thomas C, Verbeek M, Subklewe M, Peschel C, Wester HJ, Schwaiger M, Götze K, Keller U. Targeted positron emission tomography imaging of CXCR4 expression in patients with acute myeloid leukemia. Haematologica. 2016

Eichner R, Heider M, Fernández-Sáiz V, van Bebber F, Garz AK, Lemeer S, Rudelius M, Targosz BS, Jacobs L, Knorn AM, Slawska J, Platzbecker U, Germing U, Langer C, Knop S, Einsele H, Peschel C, Haass C, Keller U, Schmid B, Götze KS, Kuster B, Bassermann F. Immunomodulatory drugs disrupt the cereblon-CD147-MCT1 axis to exert antitumor activity and teratogenicity. Nat Med. 2016

Knies N, Alankus B, Weilemann A, Tzankov A, Brunner K, Ruff T, Kremer M, Keller UB, Lenz G, Ruland J. Lymphomagenic CARD11/BCL10/MALT1 signaling drives malignant B-cell proliferation via cooperative NF-κB and JNK activation. Proc Natl Acad Sci U S A. 2015

Tomiatti V, Istvánffy R, Pietschmann E, Kratzat S, Hoellein A, Quintanilla-Fend L, von Bubnoff N, Peschel C, Oostendorp RA, Keller U. Cks1 is a critical regulator of hematopoietic stem cell quiescence and cycling, operating upstream of Cdk inhibitors. Oncogene. 2015

Philipp-Abbrederis K, Herrmann K, Knop S, Schottelius M, Eiber M, Lückerath K, Pietschmann E, Habringer S, Gerngroß C, Franke K, Rudelius M, Schirbel A, Lapa C, Schwamborn K, Steidle S, Hartmann E, Rosenwald A, Kropf S, Beer AJ, Peschel C, Einsele H, Buck AK, Schwaiger M, Götze K, Wester HJ, Keller U. In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma. EMBO Mol Med. 2015

Dechow T, Steidle S, Götze KS, Rudelius M, Behnke K, Pechloff K, Kratzat S, Bullinger L, Fend F, Soberon V, Mitova N, Li Z, Thaler M, Bauer J, Pietschmann E, Albers C, Grundler R, Schmidt-Supprian M, Ruland J, Peschel C, Duyster J, Rose-John S, Bassermann F, Keller U. GP130 activation induces myeloma and collaborates with MYC. J Clin Invest. 2014

Baumann U, Fernández-Sáiz V, Rudelius M, Lemeer S, Rad R, Knorn AM, Slawska J, Engel K, Jeremias I, Li Z, Tomiatti V, Illert AL, Targosz BS, Braun M, Perner S, Leitges M, Klapper W, Dreyling M, Miething C, Lenz G, Rosenwald A, Peschel C, Keller U, Kuster B, Bassermann F. Disruption of the PRKCD-FBXO25-HAX-1 axis attenuates the apoptotic response and drives lymphomagenesis. Nat Med. 2014

Hoellein A, Fallahi M, Schoeffmann S, Steidle S, Schaub FX, Rudelius M, Laitinen I, Nilsson L, Goga A, Peschel C, Nilsson JA, Cleveland JL, Keller U. Myc-induced SUMOylation is a therapeutic vulnerability for B-cell lymphoma. Blood. 2014

den Hollander J, Rimpi S, Doherty JR, Rudelius M, Buck A, Hoellein A, Kremer M, Graf N, Scheerer M, Hall MA, Goga A, von Bubnoff N, Duyster J, Peschel C, Cleveland JL, Nilsson JA, Keller U. Aurora kinases A and B are up-regulated by Myc and are essential for maintenance of the malignant state. Blood. 2010

Funding sources

  • Deutsche Forschungsgemeinschaft (DFG)
  • Bundesministerium für Bildung und Forschung (BMBF)
  • Bundesamt für Risikobewertung (BfR)
  • Deutsche Krebshilfe
  • German Cancer Consortium (DKTK)
  • Else-Kröner-Fresenius Stiftung (EKFS)
  • Wilhelm-Sander-Stiftung
  • Stiftung Charité
  • Berlin Institute of Health (BIH)
  • Berliner Krebsgesellschaft