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You are here:  Clinics & Institutes & Centers >> Clinical facilities >> Clinics >> Center for Internal Medicine >> Forschung >> Oellerich Laboratory >>

Oellerich Laboratory

Thomas Oellerich, MD

Thomas Oellerich, MD
Department of Internal Medicine, Hematology/Oncology
University Hospital Frankfurt
Building 25, 1st floor
Theodor-Stern-Kai 7
60595 Frankfurt am Main, Germany
Tel: +49 69 / 6301 - 6148
Fax: +49 69 / 6301 - 4135
E-mail: thomas.oellerich[at]kgu.de





Carmen Döbele, PhD


Deputy Lab Head
Tel:   +49 69 / 6301 - 6148
Fax:  +49 69 / 6301 - 4135
E-mail: ca.doebele[at]med.uni-frankfurt.de

Focus of the laboratory

  • Aggressive lymphomas
  • Acute myeloid leukemia
  • Antigen receptor signal transduction
  • Clinical Proteomics

Laboratory members

Anne Wilke, née Köhler, MD: Post-doctoral fellow
Anjali Cremer, MD: Post-doctoral fellow
Sebastian Scheich, MD: Post-doctoral fellow
Kamonwan (Pear) Fish, PhD: Post-doctoral fellow
Julian Lohmeyer, MD
Silvia Münch: Technician
Bärbel Junge: Technician
Martine Pape: Technician
Alena Zindel: Technician
Laura Merschen: Technician
Sebastian Mohr: PhD Graduate Student
Roland Walter: PhD Graduate Student
Timea Török: PhD Graduate Student
Yanlong Ji: PhD Graduate Student
Tanja Wotapek: Master Student
Jessica Peter: MD Graduate Student
Khouloud Kouidri: MD Graduate Student
Johannes Kovar: MD Graduate Student

Current Projects

1) Aggressive lymphomas

We are interested in comparative analyses of normal lymphocyte development and malignant transformation towards lymphoma with a strong focus on signal transduction. Using classical molecular biology/biochemistry, proteomics, various cellular and mouse models we characterize lymphoma pathobiology in order to identify druggable signaling molecules.

2) Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) is characterized by infiltration of the bone marrow with highly proliferative myeloid progenitor cells that are arrested in their early differentiation stage. Next generation sequencing shows recurrent mutations in several functional gene classes. Resulting models postulate that impairment of transcriptional control, aberrant epigenetic modifications and DNA methylation disturbances coincide with activated signaling pathways in the course of leukemic transformation. AML-specific mutations in signaling pathways do not only drive leukemic transformation, but also cause resistance to chemotherapy. We are interested in characterizing such disease-promoting signaling events in various models and using functional approaches, such as RNA interference, to identify novel therapeutic strategies to target leukemic stem cells. Regarding therapy resistance, we investigate in particular the role of AML/bone marrow stroma interactions.

3) Antigen receptor signal transduction

Antigen receptor signaling is essential for lymphocyte development and function. To coordinate adaptive immune responses B- and T-cell receptors regulate multiple intracellular signaling proteins. We are interested to study signaling pathways downstream of antigen receptors to better understand the molecular pathways that are involved in regulation of immune cell function. As anti-cancer therapies based on chimeric antigen receptors (CARs) emerge, we also characterize CAR-mediated signaling and investigate, if modulation of CAR-dependent signals can be used to fine-tune T-cell function in order to improve their therapeutic efficacy.

4) Clinical proteomics

We characterize protein expression and signaling patterns in liquid and solid tumors by quantitative mass-spectrometry-based proteomics to identify diagnostic and predictive biomarkers. To that end we use methods for relative and absolute quantification of proteins and various post-translational modifications such as phosphorylation, ubiquitination, acetylation in collaboration with the Bioanalytical Mass Spectrometry Group (Prof. Urlaub) at the Max Planck Institute for Biophysical Chemistry Göttingen.

Research funding

  • DFG – Deutsche Forschungsgemeinschaft
  • Deutsche Krebshilfe
  • BMBF – Bundesministerium für Bildung und Forschung
  • DKTK – Deutsches Konsortium für Translationale Krebsforschung
  • LOEWE - Landes-Offensive zur Entwicklung Wissenschaftlich-ökonomischer Exzellenz
  • Bayer

Publications

2017

Mohr S*, Doebele C*, Comoglio F*, Berg T*, Beck J, Bohnenberger H, Alexe G, Corso J, Ströbel P, Wachter A, Beissbarth T, Schnütgen F, Cremer A, Haetscher N, Göllner S, Rouhi A, Palmqvist L, Rieger MA, Schroeder T, Bönig H, Müller-Tidow C, Kuchenbauer F, Schütz E, Green AR, Urlaub H, Stegmaier K, Humphries RK, Serve H, Oellerich T. Hoxa9 and Meis1 Cooperatively Induce Addiction to Syk Signaling by Suppressing miR-146a in Acute Myeloid Leukemia. Cancer Cell. 2017 Apr 10;31(4).

Walter R*, Pan KT*, Doebele C*, Comoglio F*, Tomska K, Bohnenberger H, Young RM, Jacobs L, Keller U, Bönig H, Engelke M, Rosenwald A, Urlaub H, Staudt LM, Serve H, Zenz T, Oellerich T. HSP90 promotes Burkitt lymphoma cell survival by maintaining tonic B-cell receptor signaling. Blood. 2017 Feb 2;129(5):598-608.

Schneider C*, Oellerich T*, Baldauf HM*, Schwarz SM*, Thomas D, Flick R, Bohnenberger H, Kaderali L, Stegmann L, Cremer A, Martin M, Lohmeyer J, Michaelis M, Hornung V, Schliemann C, Berdel WE, Hartmann W, Wardelmann E, Comoglio F, Hansmann ML, Yakunin AF, Geisslinger G, Ströbel P, Ferreirós N, Serve H, Keppler OT, Cinatl J Jr. SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia. Nat Med. 2017 Feb;23(2):250-255.

2016

Corso J, Pan KT, Walter R, Doebele C, Mohr S, Bohnenberger H, Ströbel P, Lenz C, Slabicki M, Hüllein J, Comoglio F, Rieger MA, Zenz T, Wienands J, Engelke M, Serve H, Urlaub H, Oellerich T. Elucidation of tonic and activated B-cell receptor signaling in Burkitt's lymphoma provides insights into regulation of cell survival. Proc Natl Acad Sci U S A. 2016 May 17;113(20):5688-93.

2015

Oellerich T, Mohr S, Corso J, Beck J, Döbele C, Braun H, Cremer A, Münch S, Wicht J, Oellerich MF, Bug G, Bohnenberger H, Perske C, Schütz E, Urlaub H, Serve H. FLT3-ITD and TLR9 employ Bruton's tyrosine kinase to activate distinct transcriptional programs mediating AML cell survival and proliferation. Blood. 2015 Jan 20.

Hanibal Bohnenberger, Philipp Ströbel, Sebastian Mohr, Jasmin Corso, Tobias Berg, Henning Urlaub, Christof Lenz, Hubert Serve, Thomas Oellerich. Quantitative Mass spectrometric profiling of cancer-cell proteomes derived from liquid and solid tumors. J. Vis. Exp. 2015.

2014

Kolodziej S, Kuvardina ON, Oellerich T, Herglotz J, Backert I, Kohrs N, Buscató El, Wittmann SK, Salinas-Riester G, Bonig H, Karas M, Serve H, Proschak E, Lausen J.PADI4 acts as a coactivator of Tal1 by counteracting repressive histone arginine methylation. Nat Commun. 2014 May 29;5:3995.

Berg T, Thoene S, Yap D, Wee T, Schoeler N, Rosten P, Lim E, Bilenky M, Mungall AJ, Oellerich T, Lee S, Lai CK, Umlandt P, Salmi A, Chang H, Yue L, Lai D, Cheng SW, Morin RD, Hirst M, Serve H, Marra MA, Morin GB, Gascoyne RD, Aparicio SA, Humphries RK. A transgenic mouse model demonstrating the oncogenic role of mutations in the polycomb-group gene EZH2 in lymphomagenesis. Blood. 2014 Jun 19;123(25):3914-24.

Schaab C, Oppermann FS, Klammer M, Pfeifer H, Tebbe A, Oellerich T, Krauter J, Levis M, Perl AE, Daub H, Steffen B, Godl K, Serve H. Global phosphoproteome analysis of human bone marrow reveals predictive phosphorylation markers for the treatment of acute myeloid leukemia with quizartinib. Leukemia. 2014 Mar;28(3):716-9.

2013

Engelke M*, Oellerich T*, Dittmann K, Hsiao HH, Urlaub H, Serve H, Griesinger C, Wienands J.Cutting edge: feed-forward activation of phospholipase Cγ2 via C2 domain-mediated binding to SLP65. J Immunol. 2013 Dec 1;191(11):5354-8.

Castello A, Gaya M, Tucholski J, Oellerich T, Lu KH, Tafuri A, Pawson T, Wienands J, Engelke M, Batista FD. Nck-mediated recruitment of BCAP to the BCR regulates the PI(3)K-Akt pathway in B cells. Nat Immunol. 2013 Sep;14(9):966-75.

Oellerich T, Oellerich MF, Engelke M, Münch S, Mohr S, Nimz M, Hsiao HH, Corso J, Zhang J, Bohnenberger H, Berg T, Rieger MA, Wienands J, Bug G, Brandts C, Urlaub H, Serve H. β2 integrin-derived signals induce cell survival and proliferation of AML blasts by activating a Syk/STAT signaling axis. Blood. 2013 May 9;121(19):3889-99, S1-66.

Lösing M, Goldbeck I, Manno B, Oellerich T, Schnyder T, Bohnenberger H, Stork B, Urlaub H, Batista FD, Wienands J, Engelke M. The Dok-3/Grb2 protein signal module attenuates Lyn kinase-dependent activation of Syk kinase in B cell antigen receptor microclusters. J Biol Chem. 2013 Jan 25;288(4):2303-13.

2012

Batsukh T, Schulz Y, Wolf S, Rabe TI, Oellerich T, Urlaub H, Schaefer IM, Pauli S. Identification and characterization of FAM124B as a novel component of a CHD7 and CHD8 containing complex. PLoS One. 2012;7(12):e52640.

Urbich C, Kaluza D, Frömel T, Knau A, Bennewitz K, Boon RA, Bonauer A, Doebele C, Boeckel JN, Hergenreider E, Zeiher AM, Kroll J, Fleming I, Dimmeler S. MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A. Blood. 2012 Feb 9;119(6):1607-16.

Pullamsetti SS, Doebele C, Fischer A, Savai R, Kojonazarov B, Dahal BK, Ghofrani HA, Weissmann N, Grimminger F, Bonauer A, Seeger W, Zeiher AM, Dimmeler S, Schermuly RT. Inhibition of microRNA-17 improves lung and heart function in experimental pulmonary hypertension. Am J Respir Crit Care Med. 2012 Feb 15;185(4):409-19.

2011

Oellerich T, Bremes V, Neumann K, Bohnenberger H, Dittmann K, Hsiao HH, Engelke M, Schnyder T, Batista FD, Urlaub H, Wienands J. The B-cell antigen receptor signals through a preformed transducer module of SLP65 and CIN85. EMBO J. 2011 Aug 5;30(17):3620-34.

Sela M, Bogin Y, Beach D, Oellerich T, Lehne J, Smith-Garvin JE, Okumura M, Starosvetsky E, Kosoff R, Libman E, Koretzky G, Kambayashi T, Urlaub H, Wienands J, Chernoff J, Yablonski D. Sequential phosphorylation of SLP-76 at tyrosine 173 is required for activation of T and mast cells. EMBO J. 2011 Jul 1;30(15):3160-72.

Schnyder T, Castello A, Feest C, Harwood NE, Oellerich T, Urlaub H, Engelke M, Wienands J, Bruckbauer A, Batista FD.B cell receptor-mediated antigen gathering requires ubiquitin ligase Cbl and adaptors Grb2 and Dok-3 to recruit dynein to the signaling microcluster. Immunity. 2011 Jun 24;34(6):905-18.

Bohnenberger H, Oellerich T*, Engelke M, Hsiao HH, Urlaub H, Wienands J. Complex phosphorylation dynamics control the composition of the Syk interactome in B cells. Eur J Immunol. 2011 Jun;41(6):1550-62. Neumann K, Oellerich T, Heine I, Urlaub H, Engelke M. Fc gamma receptor IIb modulates the molecular Grb2 interaction network in activated B cells. Cell Signal. 2011 May;23(5):893-900.

2010

Doebele C, Bonauer A, Fischer A, Scholz A, Reiss Y, Urbich C, Hofmann WK, Zeiher AM, Dimmeler S.Members of the microRNA-17-92 cluster exhibit a cell-intrinsic antiangiogenic function in endothelial cells. Blood. 2010 Jun 10;115(23):4944-50.

Vafaizadeh V, Klemmt P, Brendel C, Weber K, Doebele C, Britt K, Grez M, Fehse B, Desriviéres S, Groner B Mammary epithelial reconstitution with gene-modified stem cells assigns roles to Stat5 in luminal alveolar cell fate decisions, differentiation, involution, and mammary tumor formation. Stem Cells. 2010 May;28(5):928-38.

2009

Bonauer A, Carmona G, Iwasaki M, Mione M, Koyanagi M, Fischer A, Burchfield J, Fox H, Doebele C, Ohtani K, Chavakis E, Potente M, Tjwa M, Urbich C, Zeiher AM, Dimmeler S. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science. 2009 Jun 26;324(5935):1710-3.

Neumann K, Oellerich T, Urlaub H, Wienands J. The B-lymphoid Grb2 interaction code. Immunol Rev. 2009 Nov;232(1):135-49.

Oellerich T, Grønborg M, Neumann K, Hsiao HH, Urlaub H, Wienands J. SLP-65 phosphorylation dynamics reveals a functional basis for signal integration by receptor-proximal adaptor proteins. Mol Cell Proteomics. 2009 Jul;8(7):1738-50.

* denotes equal contribution

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