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Ulrich Rothbauer
Prof. Dr. Ulrich Rothbauer
Diplom-Biologe
Joint Professorship Zelluläre Screening Modelle
Tel.: 07121 51530-415
Fax: 07121 51530-16

Employment:
Since 11/2011 Professor for Pharmaceutical Biotechnology at the University of Tuebingen
(Joint Professorship with the Natural and Medical Sciences Institute
at the University of Tuebingen, NMI)

2008 – 2011 CEO of the Biotech company ChromoTek GmbH (Martinsried)

2008 – 2010 Junior Group leader, GO-Bio, Department of Biology, LMU

2006 – 2007 Project leader „Chromobodies“ Exist Seed Group, Department of Biology, LMU

2004 – 2005 Postdoctoral Fellow, Department of Biology, LMU, in the lab of Prof. Dr Heinrich Leonhardt

2003 – 2004 Postdoctoral Fellow, Institute of Diabetic Research Academic Hospital,
Munich in the lab of PD Dr. Mathias Bauer

Education:
1999 – 2003 Dissertation (Dr. rer. nat.; PhD) at the Institute of physiological Chemistry,
LMU in the lab of Prof. Dr. Dr. Walter Neupert: Functional characterization
of a mitochondrial mediate disease:
The role of DDP1 and Tim13 for mitochondrial biogenesis

1992 – 1998 Studies in biology at the Ludwig Maximillians University Munich (LMU)

1998 Diploma degree in biology in the lab of Prof. Dr. Svante Pääbo:
In vitro processing of overlapping tRNA transcripts in human mitochondria


Research
The understanding of cellular processes in response to external stimuli is one of the major challenges biomedical research and early drug discovery. To visualize dynamic processes in real time we employ and develop a new format of intracellular functional antibodies (Chromobodies) based on single domain antibodies derived from camelids. In combination with High-Throughput Microscopy and automated image analysis we show that Chromobodies can be used to target and trace endogenous antigens in living cells. Current studies include cell cycle monitoring, real time apoptosis studies, signaling, cancer models as well as the detection of posttranslational modifications.
Our research is focused on the development of novel cellular assays based on the chromobody technology to screen for pharmaceutical relevant compounds in early drug development. In addition we are generating nanobodies as versatile tools for efficient biochemical analysis of cellular proteins and automated immunodiagnostics.

Grants:
BMBF „Validierung des Innovationspotenzials wissenschaftlicher Forschung VIP“: Validierung eines neuen, innovativen Verfahrens zum Nachweis komplexer regulatorischer Netzwerke in Tumorgewebe (October 2013), FKZ: 03V0798 / Fördersumme: 744.110 €

DFG: Vollautomatisierte Mikroskopie-basierte zelluläre High-Content Analyse Plattform für Lebendzell-Mikroskopie (February 2012), FKZ: INST 37/822-1 / Fördersumme (DFG-Anteil): 237.500 €

BMBF: Go-Bio Förderpreis II “Chromobodies: Innovative biomedizinische Forschung und Diagnostik mit fluoreszierenden Nanobodies” Förderkennzeichen: 0315109 / Fördersumme: 1.200.000 € (January 2011)

BMBF: Go-Bio Förderpreis I “Chromobodies: Innovative biomedizinische Forschung und Diagnostik mit fluoreszierenden Nanobodies” Förderkennzeichen: 0315109 / Fördersumme: 1.500.000 € (January 2008)

Awards:
- 2007 Publication Award (Center for NanoScience, LMU)
- 2007 GO-Bio Award I of the Federal Ministry of Education and Research (BMBF)
- 2008 Binder Innovation-Award (German Society of Cell Biology, DGZ)
- 2010 Publication Award (Center for NanoScience, LMU)
- 2010 GO-Bio Award II of the BMBF
- 2012 Award of the Innovation-Academy (BMBF)

Memberships
Since 2001 Society for Biochemistry and Molecularbiology (GBM)
Since 2009 Center for NanoScience (CeNS)
Since 2010 Society for Biomolecular Screening (SBS)
Since 2012 Dechema (Frankfurt)

Miscellanous
Reviewer for Proteomics, BMC, Nature Structural and Molecular Biology, Analytical Chemistry

Member of the Supervisory Board of BIOPRO GmbH

Publication List

Publications (in progress)

Braun M.B., Koch P.A., Emele F., Traenkle B., Weiss F., Poetz O., Stehle T., Rothbauer U. Peptides in headlock – a novel high-affinity peptide-binding nanobody for proteomics and microscopy (in preparation)

Buchfellner A, Yurlova L., Nueske S., Scholz A., Bogner J., Ruf B., Zolghadr K., Romer T., Friedl A. Rothbauer U. A new nanobody-based biosensor to study endogenous PARP1 in vitro and in live human cells (in preparation)

Rajan M., Mortusewicz O. Rothbauer U., Schmidthals K., Rapp A., Leonhardt H., Cardoso C. In vivo epitope recognition pitfalls affect y.H2AX chromobody function in living cells (submitted to Biochemical and Biophysical Research Communications)

Sinnberg T., Makino E., Krueger M.A., Velic A., Macek B., Rothbauer U., Groll N., Poetz O., Czemmel S., Niessner H., Meier F., Schittek B. A novel nexus consisting of beta-catenin and Stat3 attenuates BRAF inhibitor efficacy and mediates secondary resistance to vemurafenib (submitted to Cancer Research)

Maier J., Traenkle B., Rothbauer U. Real-time analysis of epithelial-mesenchymal transition using fluorescent nanobodies (Scientific Reports, in revision)

Bauer S.M., Kubiak J.M., Rothbauer U., Laufer SA, (2015) From Enzyme to Whole Blood: Sequential Screening Procedure for Identification and Evaluation of p38 MAPK Inhibitors. Methods in Molecular Biology (accepted)

Publications (published)

46. Panza P, Maier J, Schmees C, Rothbauer U*, Söllner C*. Live imaging of endogenous protein dynamics in zebrafish using chromobodies. Development. 2015 May 15;142(10):1879-84

45. Groll N, Emele F, Poetz O, Rothbauer U. Towards multiplexed protein-protein interaction analysis using protein tag-specific nanobodies. J Proteomics. 2015 May 1. pii: S1874-3919(15)00198-0.

44. Traenkle B, Emele F, Anton R, Poetz O, Haeussler RS, Maier J, Kaiser PD, Scholz AM, Nueske S, Buchfellner A, Romer T, Rothbauer U. Monitoring interactions and dynamics of endogenous beta-catenin with intracellular nanobodies in living cells. Mol Cell Proteomics. 2015 Mar;14(3):707-23.

43. Borg S, Popp F, Hofmann J, Leonhardt H, Rothbauer U, Schüler D. An intracellular nanotrap redirects proteins and organelles in live bacteria. MBio. 2015 Jan 13;6(1). pii: e02117-14.

42. Muth F, Günther M, Bauer SM, Döring E, Fischer S, Maier J, Drückes P, Köppler J, Trappe J, Rothbauer U, Koch P, Laufer SA. Tetra-substituted pyridinylimidazoles as dual inhibitors of p38α mitogen-activated protein kinase and c-Jun N-terminal kinase 3 for potential treatment of neurodegenerative diseases. J Med Chem. 2015 Jan 8;58(1):443-56

41. Kaiser PD, Maier J, Traenkle B, Emele F, Rothbauer U. Recent progress in generating intracellular functional antibody fragments to target and trace cellular components in living cells. Biochim Biophys Acta. 2014 Nov;1844(11):1933-1942

40. Anton R, Bauer SM, Keck PR, Laufer S, Rothbauer U. A p38 substrate-specific MK2-EGFP translocation assay for identification and validation of new p38 inhibitors in living cells: a comprising alternative for acquisition of cellular p38 inhibition data. PLoS One. 2014 Apr 17;9(4):e95641

39. Strein C, Alleaume AM, Rothbauer U, Hentze MW, Castello A. A versatile assay for RNA-binding proteins in living cells. RNA. 2014 May;20(5):721-31.

38. Yurlova L, Derks M, Buchfellner A, Hickson I, Janssen M, Morrison D, Stansfield I, Brown CJ, Ghadessy FJ, Lane DP, Rothbauer U, Zolghadr K, Krausz E. The fluorescent two-hybrid assay to screen for protein-protein interaction inhibitors in live cells: targeting the interaction of p53 with Mdm2 and Mdm4. J Biomol Screen. 2014 Apr;19(4):516-25

37. Gustems M, Woellmer A, Rothbauer U, Eck SH, Wieland T, Lutter D, Hammerschmidt W. c-Jun/c-Fos heterodimers regulate cellular genes via a newly identified class of methylated DNA sequence motifs. Nucleic Acids Res. 2014 Mar;42(5):3059-72.

36. Helma J, Schmidthals K, Lux V, Nüske S, Scholz AM, Kräusslich HG, Rothbauer U*, Leonhardt H*. Direct and dynamic detection of HIV-1 in living cells. PLoS One. 2012;7(11):e50026

35. Schlossbauer A, Sauer AM, Cauda V, Schmidt A, Engelke H, Rothbauer U, Zolghadr K, Leonhardt H, Bräuchle C, Bein T. Cascaded photoinduced drug delivery to cells from multifunctional core-shell mesoporous silica. Adv Healthc Mater. 2012 May;1(3):316-20

34. Zolghadr K, Gregor J, Leonhardt H, Rothbauer U. Case study on live cell apoptosis-assay using lamin-chromobody cell-lines for high-content analysis. Methods Mol Biol. 2012;911:569-75

33. Pichler G, Leonhardt H, Rothbauer U. Fluorescent protein specific Nanotraps to study protein-protein interactions and histone-tail peptide binding. Methods Mol Biol. 2012;911:475-83

32. Pellis M, Pardon E, Zolghadr K, Rothbauer U, Vincke C, Kinne J, Dierynck I, Hertogs K, Leonhardt H, Messens J, Muyldermans S, Conrath K. A bacterial-two-hybrid selection system for one-step isolation of intracellularly functional Nanobodies. Arch Biochem Biophys. 2012 Oct 15;526(2):114-23

31. Zolghadr K, Rothbauer U, Leonhardt H. The fluorescent two-hybrid (F2H) assay for direct analysis of protein-protein interactions in living cells. Methods Mol Biol. 2012;812:275-82

30. Wälde S, Thakar K, Hutten S, Spillner C, Nath A, Rothbauer U, Wiemann S, Kehlenbach RH. The nucleoporin Nup358/RanBP2 promotes nuclear import in a cargo- and transport receptor-specific manner. Traffic. 2012 Feb;13(2):218-33.

29. Pollithy A, Romer T, Lang C, Müller FD, Helma J, Leonhardt H, Rothbauer U, Schüler D. Magnetosome expression of functional camelid antibody fragments (nanobodies) in Magnetospirillum gryphiswaldense. Appl Environ Microbiol. 2011 Sep;77(17):6165-71

28. Romer T, Leonhardt H, Rothbauer U. Engineering antibodies and proteins for molecular in vivo imaging. Curr Opin Biotechnol. 2011 Dec;22(6):882-7

27. Wienken CJ, Baaske P, Rothbauer U, Braun D, Duhr S. Protein-binding assays in biological liquids using microscale thermophoresis. Nature Commun. 2010 Oct 19;1:100

26. Bergbauer M, Kalla M, Schmeinck A, Göbel C, Rothbauer U, Eck S, Benet-Pagès A, Strom TM, Hammerschmidt W. CpG-methylation regulates a class of Epstein-Barr virus promoters. PLoS Pathog. 2010 Sep 23;6(9):e1001114.

25. Schmidthals K, Helma J, Zolghadr K, Rothbauer U*, Leonhardt H*. Novel antibody derivatives for proteome and high-content analysis. Anal Bioanal Chem. 2010 Aug;397(8):3203-8.

24. Resemann A, Wunderlich D, Rothbauer U, Warscheid B, Leonhardt H, Fuchser J, Kuhlmann K, Suckau D. Top-down de Novo protein sequencing of a 13.6 kDa camelid single heavy chain antibody by matrix-assisted laser desorption ionization-time-of-flight/time-of-flight mass spectrometry. Anal Chem. 2010 Apr 15;82(8):3283-92

23. Geiger J, Aneja MK, Hasenpusch G, Yüksekdag G, Kummerlöwe G, Luy B, Romer T, Rothbauer U, Rudolph C. Targeting of the prostacyclin specific IP1 receptor in lungs with molecular conjugates comprising prostaglandin I2 analogues. Biomaterials. 2010 Apr;31(10):2903-11

22. Kirchhofer A, Helma J, Schmidthals K, Frauer C, Cui S, Karcher A, Pellis M, Muyldermans S, Casas-Delucchi CS, Cardoso MC, Leonhardt H, Hopfner KP, Rothbauer U. Modulation of protein properties in living cells using nanobodies. Nature Structural Mol Biol. 2010 Jan;17(1):133-8

21. Meilinger D, Fellinger K, Bultmann S, Rothbauer U, Bonapace IM, Klinkert WE, Spada F, Leonhardt H. Np95 interacts with de novo DNA methyltransferases, Dnmt3a and Dnmt3b, and mediates epigenetic silencing of the viral CMV promoter in embryonic stem cells. EMBO Rep. 2009 Nov;10(11):1259-64

20. Schornack S, Fuchs R, Huitema E, Rothbauer U, Lipka V, Kamoun S. Protein mislocalization in plant cells using a GFP-binding chromobody. Plant J. 2009 Nov;60(4):744-54

19. Fellinger K, Rothbauer U, Felle M, Längst G, Leonhardt H. Dimerization of DNA methyltransferase 1 is mediated by its regulatory domain. J Cell Biochem. 2009 Mar 1;106(4):521-8

18. Muyldermans S, Baral TN, Retamozzo VC, De Baetselier P, De Genst E, Kinne J, Leonhardt H, Magez S, Nguyen VK, Revets H, Rothbauer U, Stijlemans B, Tillib S, Wernery U, Wyns L, Hassanzadeh-Ghassabeh G, Saerens D. Camelid immunoglobulins and nanobody technology. Vet Immunol Immunopathol. 2009 Mar
15;128(1-3):178-83

17. Trinkle-Mulcahy L, Boulon S, Lam YW, Urcia R, Boisvert FM, Vandermoere F, Morrice NA, Swift S, Rothbauer U, Leonhardt H, Lamond A. Identifying specific protein interaction partners using quantitative mass spectrometry and bead proteomes. J Cell Biol. 2008 Oct 20;183(2):223-39

16. Rottach A, Kremmer E, Nowak D, Boisguerin P, Volkmer R, Cardoso MC, Leonhardt H, Rothbauer U. Generation and characterization of a rat monoclonal antibody specific for PCNA. Hybridoma (Larchmt). 2008 Apr;27(2):91-8.

15. Zolghadr K, Mortusewicz O, Rothbauer U, Kleinhans R, Goehler H, Wanker EE, Cardoso MC, Leonhardt H. A fluorescent two-hybrid assay for direct visualization of protein interactions in living cells. Mol Cell Proteomics. 2008 Nov;7(11):2279-87

14. Rothbauer U, Zolghadr K, Muyldermans S, Schepers A, Cardoso MC, Leonhardt H. A versatile nanotrap for biochemical and functional studies with fluorescent fusion proteins. Mol Cell Proteomics. 2008 Feb;7(2):282-9

13. Agarwal N, Hardt T, Brero A, Nowak D, Rothbauer U, Becker A, Leonhardt H, Cardoso MC. MeCP2 interacts with HP1 and modulates its heterochromatin association during myogenic differentiation. Nucleic Acids Res. 2007;35(16):5402-8

12. Schermelleh L, Haemmer A, Spada F, Rösing N, Meilinger D, Rothbauer U, Cardoso MC, Leonhardt H. Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation. Nucleic Acids Res. 2007;35(13):4301-12

11. Spada F, Haemmer A, Kuch D, Rothbauer U, Schermelleh L, Kremmer E, Carell T, Längst G, Leonhardt H. DNMT1 but not its interaction with the replication machinery is required for maintenance of DNA methylation in human cells. J Cell Biol. 2007 Feb 26;176(5):565-71

10. Rothbauer U, Zolghadr K, Tillib S, Nowak D, Schermelleh L, Gahl A, Backmann N, Conrath K, Muyldermans S, Cardoso MC, Leonhardt H. Targeting and tracing antigens in live cells with fluorescent nanobodies. Nature Methods. 2006 Nov;3(11):887-9.

9. Spada F, Rothbauer U, Zolghadr K, Schermelleh L, Leonhardt H. Regulation of DNA methyltransferase 1. Adv Enzyme Regul. 2006;46:224-34.

8. Mortusewicz O, Rothbauer U, Cardoso MC, Leonhardt H. Differential recruitment of DNA Ligase I and III to DNA repair sites. Nucleic Acids Res. 2006 Jul 19;34(12):3523-32

7. Hofmann S*, Rothbauer U*, Mühlenbein N, Baiker K, Hell K, Bauer MF. Functional and mutational characterization of human MIA40 acting during import into the mitochondrial intermembrane space. J Mol Biol. 2005 Oct 28;353(3):517-28.

6. Mühlenbein N, Hofmann S, Rothbauer U, Bauer MF. Organization and function of the small Tim complexes acting along the import pathway of metabolite carriers into mammalian mitochondria. J Biol Chem. 2004 Apr 2;279(14):13540-6

5. Hofmann S*, Rothbauer U*, Mühlenbein N, Neupert W, Gerbitz KD, Brunner M, Bauer MF. The C66W mutation in the deafness dystonia peptide 1 (DDP1) affects the formation of functional DDP1.TIM13 complexes in the mitochondrial intermembrane space. J Biol Chem. 2002 Jun 28;277(26):23287-93

4. Rothbauer U, Hofmann S, Mühlenbein N, Paschen SA, Gerbitz KD, Neupert W, Brunner M, Bauer MF. Role of the deafness dystonia peptide 1 (DDP1) in import of human Tim23 into the inner membrane of mitochondria. J Biol Chem. 2001 Oct 5;276(40):37327-34

3. Paschen SA, Rothbauer U, Káldi K, Bauer MF, Neupert W, Brunner M. The role of the TIM8-13 complex in the import of Tim23 into mitochondria. EMBO J. 2000 Dec 1;19(23):6392-400.

2. Bauer MF, Rothbauer U, Mühlenbein N, Smith RJ, Gerbitz K, Neupert W, Brunner M, Hofmann S. The mitochondrial TIM22 preprotein translocase is highly conserved throughout the eukaryotic kingdom. FEBS Lett. 1999 Dec 24;464(1-2):41-7.

1. Reichert A, Rothbauer U, Mörl M. Processing and editing of overlapping tRNAs in human mitochondria. J Biol Chem. 1998 Nov 27;273(48):31977-84.

* both authors are contributed equally to this work

Patents
Rothbauer U., Leonhardt H., Zolghadr K., Mortusewicz O. (2009)
Fluorescent two-hybrid (F2Hh) assay for direct visualization of protein interactions in living cells
WO2009087097A1/ EP2078750A1 / US20100285487 / CA2709701A1

Rothbauer U., Leonhardt H. (2005)
Targeting and tracing of antigens in living cells
WO2007068313A2 / EP1945673B1 / US20090136934

Rothbauer U., Leonhardt H., Zolghadr K., Romer T., Schmidthals K. (2010)
Detection and visualization of the cell cycle in living cells
WO 2011003896 A1 / EP 2451841 B1 / US 8999669 B2

Publikationen

Groll, N., Emele, F., Poetz, O., Rothbauer, U. (2015).
Towards multiplexed protein-protein interaction analysis using protein tag-specific nanobodies
J Proteomics. 2015 Sep 8;127(Pt B):289-99. doi: 10.1016/j.jprot.2015.04.017. Epub 2015 May 1.

Sinnberg, T., Makino, E., Krueger, M. A., Velic, A., Macek, B., Rothbauer, U., Groll, N., Potz, O., Czemmel, S., Niessner, H., Meier, F., Ikenberg, K., Garbe, C., Schittek, B. (2016).
A Nexus Consisting of Beta-Catenin and Stat3 Attenuates BRAF Inhibitor Efficacy and Mediates Acquired Resistance to Vemurafenib
EBioMedicine. 2016 Jun;8:132-49. doi: 10.1016/j.ebiom.2016.04.037. Epub 2016 May 1.

Groll, N., Petrikat, T., Vetter, S., Colnot, S., Weiss, F., Poetz, O., Joos, T. O., Rothbauer, U., Schwarz, M., Braeuning, A. (2016).
Coordinate regulation of Cyp2e1 by beta-catenin- and hepatocyte nuclear factor 1alpha-dependent signaling
Toxicology. 2016 Mar 28;350-352:40-8. doi: 10.1016/j.tox.2016.05.004. Epub 2016 May 3.

Sannino, G., Armbruster, N., Bodenhofer, M., Haerle, U., Behrens, D., Buchholz, M., Rothbauer, U., Sipos, B., Schmees, C. (2016).
Role of BCL9L in transforming growth factor-beta (TGF-beta)-induced epithelial-to-mesenchymal-transition (EMT) and metastasis of pancreatic cancer
Oncotarget. 2016 Oct 4. doi: 10.18632/oncotarget.12455.

Maier, J., Traenkle, B., Rothbauer, U. (2016).
Visualizing Epithelial-Mesenchymal Transition Using the Chromobody Technology
Cancer Res. 2016 Sep 15.

Traenkle, B., Kaiser, P. D., Rothbauer, U. (2016).
Nanobody Platform for Determination of Protein Structure, Application of Peptides and Proteins
Encyclopedia of Analytical Chemistry, John Wiley & Sons, Ltd.

Buchfellner, A., Yurlova, L., Nuske, S., Scholz, A. M., Bogner, J., Ruf, B., Zolghadr, K., Drexler, S. E., Drexler, G. A., Girst, S., Greubel, C., Reindl, J., Siebenwirth, C., Romer, T., Friedl, A. A., Rothbauer, U. (2016).
A New Nanobody-Based Biosensor to Study Endogenous PARP1 In Vitro and in Live Human Cells
PLoS One. 2016 Mar 7;11(3):e0151041. doi: 10.1371/journal.pone.0151041. eCollection 2016.

Bauer, S. M., Kubiak, J. M., Rothbauer, U., Laufer, S. (2016).
From Enzyme to Whole Blood: Sequential Screening Procedure for Identification and Evaluation of p38 MAPK Inhibitors
Methods Mol Biol. 2016;1360:123-48. doi: 10.1007/978-1-4939-3073-9_10.

Rajan, M., Mortusewicz, O., Rothbauer, U., Hastert, F. D., Schmidthals, K., Rapp, A., Leonhardt, H., Cardoso, M. C. (2015).
Generation of an alpaca-derived nanobody recognizing gamma-H2AX
FEBS Open Bio. 2015 Sep 21;5:779-88. doi: 10.1016/j.fob.2015.09.005. eCollection 2015.

Schorpp, K., Rothenaigner, I., Maier, J., Traenkle, B., Rothbauer, U., Hadian, K. (2016).
A Multiplexed High-Content Screening Approach Using the Chromobody Technology to Identify Cell Cycle Modulators in Living Cells
J Biomol Screen. 2016 Apr 4. pii: 1087057116641935.

Braun, M. B., Traenkle, B., Koch, P. A., Emele, F., Weiss, F., Poetz, O., Stehle, T., Rothbauer, U. (2016).
Peptides in headlock - a novel high-affinity and versatile peptide-binding nanobody for proteomics and microscopy
Sci Rep. 2016 Jan 21;6:19211. doi: 10.1038/srep19211.

Maier, J., Traenkle, B., Rothbauer, U. (2015).
Real-time analysis of epithelial-mesenchymal transition using fluorescent single-domain antibodies
Sci Rep. 2015 Aug 21;5:13402. doi: 10.1038/srep13402.

Traenkle, B., Emele, F., Anton, R., Poetz, O., Haeussler, R. S., Maier, J., Kaiser, P. D., Scholz, A. M., Nueske, S., Buchfellner, A., Romer, T., Rothbauer, U. (2015).
Monitoring interactions and dynamics of endogenous beta-catenin with intracellular nanobodies in living cells
Mol Cell Proteomics. 2015 Mar;14(3):707-23. doi: 10.1074/mcp.M114.044016. Epub 2015 Jan 16.

Kaiser, P. D., Maier, J., Traenkle, B., Emele, F., Rothbauer, U. (2014).
Recent progress in generating intracellular functional antibody fragments to target and trace cellular components in living cells
Biochim Biophys Acta. 2014 Nov;1844(11):1933-1942. doi: 10.1016/j.bbapap.2014.04.019. Epub 2014 May 2.

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