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Tumorzentrum Freiburg - CCCF

Prof. Roland Schüle, PhD

Contact:

Department of Urology
Head of Center for Clinical Research,
University Freiburg Medical Center
Breisacherstraße 66
D-79106 Freiburg
Germany
Tel: +49 (761) 270 63100
roland.schuele@uniklinik-freiburg.de

Current Positions:

Full Professor and Scientific Director
Head of Center for Clinical Research
Medical Center University of Freiburg
Department of Urology
Speaker of the CRC 992 Medical Epigenetics
Member executive committee DKTK

Research Focus:

LSD1 Regulation

Enzym lysine-specific demethylase 1 (LSD1) is a gatekeeper for differentiation onset of embryonic mouse stem cells which acts by demethylation of histones. (Lsd1) removes the methyl group from the amino acid lysine in histones and is a key regulator of stem cells
Lsd1 regulates two functions in cell genesis, the ability to migrate and to correctly differentiate.
Prof. Schüles working group is specifically focused on finding out whether this is due to the removal of methyl groups from the chromatin or more likely due to the lack of demethylation. The group aims to obtain detailed information about the role of LSD1 by specifically looking at the dysregulation of it. As overexpression of LSD1 leads to the development of prostate and lung tumours in old mice the researchers will focus on finding out why this happens.

  • Basic epigenetic mechanisms in cellular assays and explorative mouse models
  • Validation of epigenetic control in animal models of disease
  • Transfer of epigenetic principles to clinical applications


CRC 992, Principal Investigator Project B01: The epigenetic regulator LSD1 controls tumorgenesis
http://www.sfb992.uni-freiburg.de/

CRC 850, Project B3: Migration and invasion policed by the histone demethylase LSD1
Member of the BIOSS Centre for Biological Signaling Studies

DKTK Research Topics

  • Epigenetics/histone modifications
  • Inhibitors of histone code reader proteins
  • LACID: LSD1 as anticancer target in the clinic (TRANSATRA) and in drug discovery

DKTK Research Platform Drug Development:

LSD1 inhibitors as new anticancer agents

Working Group Members DKTK:

Dr. Eric Metzger   
Thomas Günther

http://www.uniklinik-freiburg.de/schuelelab.html

http://www.sfb992.uni-freiburg.de/people/roland-schule

DKTK Publications:

Wagner T, Greschik H, Burgahn T, Schmidtkunz K, Schott A-K, McMillan J, Baranauskienė L, Xiong Y, Fedorov O, Jin J, Oppermann U, Matulis D, Schüle R, Jung M. Identification of a small-molecule ligand of the epigenetic reader protein Spindlin1 via a versatile screening platform. Nucleic Acids Research. 17. Februar 2016;gkw089. 

Slynko I, Schmidtkunz K, Rumpf T, Klaeger S, Heinzlmeir S, Najar A, Metzger E, Kuster B, Schüle R, Jung M, Sippl W. Identification of Highly Potent Protein Kinase C-Related Kinase 1 Inhibitors by Virtual Screening, Binding Free Energy Rescoring, and in vitro Testing. ChemMedChem [Internet]. Juli 2016 [zitiert 5. August 2016]; Verfügbar unter: http://doi.wiley.com/10.1002/cmdc.201600284

Robaa D, Wagner T, Luise C, Carlino L, McMillan J, Flaig R, Schüle R, Jung M, Sippl W. Identification and Structure-Activity Relationship Studies of Small-Molecule Inhibitors of the Methyllysine Reader Protein Spindlin1. ChemMedChem [Internet]. September 2016 [zitiert 7. Oktober 2016]; Verfügbar unter: http://doi.wiley.com/10.1002/cmdc.201600362 

Ostrovskyi D, Rumpf T, Eib J, Lumbroso A, Slynko I, Klaeger S, Heinzlmeir S, Forster M, Gehringer M, Pfaffenrot E, Bauer SM, Schmidtkunz K, Wenzler S, Metzger E, Kuster B, Laufer S, Schüle R, Sippl W, Breit B, Jung M. Tofacitinib and analogs as inhibitors of the histone kinase PRK1 (PKN1). Future Medicinal Chemistry [Internet]. 30. August 2016 [zitiert 5. September 2016]; Verfügbar unter: www.future-science.com/doi/10.4155/fmc-2016-0132

Duteil D, Tosic M, Lausecker F, Nenseth HZ, Müller JM, Urban S, Willmann D, Petroll K, Messaddeq N, Arrigoni L, Manke T, Kornfeld J-W, Brüning JC, Zagoriy V, Meret M, Dengjel J, Kanouni T, Schüle R. Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue. Cell Reports. Oktober 2016;17(4):1008–21. 

Greve G, Schiffmann I, Pfeifer D, Pantic M, Schüler J, Lübbert M. The pan-HDAC inhibitor panobinostat acts as a sensitizer for erlotinib activity in EGFR-mutated and -wildtype non-small cell lung cancer cells. BMC Cancer [Internet]. Dezember 2015 [zitiert 7. Januar 2016];15(1). Verfügbar unter: www.biomedcentral.com/1471-2407/15/947

Franz H, Greschik H, Willmann D, Ozretić L, Jilg CA, Wardelmann E, Jung M, Buettner R, Schüle R. The histone code reader SPIN1 controls RET signaling in liposarcoma. Oncotarget. 6. März 2015;

Duteil D, Metzger E, Willmann D, Karagianni P, Friedrichs N, Greschik H, u. a. LSD1 promotes oxidative metabolism of white adipose tissue. Nature Communications [Internet]. 10. Juni 2014 [zitiert 13. Juni 2014];5. Verfügbar unter: www.nature.com/doifinder/10.1038/ncomms5093

Nam HJ, Boo K, Kim D, Han D-H, Choe HK, Kim CR, u. a. Phosphorylation of LSD1 by PKCα Is Crucial for Circadian Rhythmicity and Phase Resetting. Molecular Cell. März 2014;53(5):791–805.

Schmitt ML, Ladwein KI, Carlino L, Schulz-Fincke J, Willmann D, Metzger E, u. a. Heterogeneous Antibody-Based Activity Assay for Lysine Specific Demethylase 1 (LSD1) on a Histone Peptide Substrate. Journal of Biomolecular Screening [Internet]. 31. März 2014 [zitiert 11. Juni 2014]; Verfügbar unter: jbx.sagepub.com/cgi/doi/10.1177/1087057114529156

Zhu D, Hölz S, Metzger E, Pavlovic M, Jandausch A, Jilg C, u. a. Lysine-specific demethylase 1 regulates differentiation onset and migration of trophoblast stem cells. Nature Communications [Internet]. 22. Januar 2014 [zitiert 11. Juni 2014];5. Verfügbar unter: www.nature.com/doifinder/10.1038/ncomms4174

Ketscher A, Jilg CA, Willmann D, Hummel B, Imhof A, Rüsseler V, u. a. LSD1 controls metastasis of androgen-independent prostate cancer cells through PXN and LPAR6. ONCOGENESIS. 6. Oktober 2014;3(10):e120–e120.

Other:

Friedrichs, J., Fink, D., Mauch, C., Kindler, K., Hartmann, W., Schüle, R., Buettner, R. and  Friedrichs, N. (2014) TGF-β1-dependent induction and nuclear translocation of FHL2 promotes keratin expression in pilomatricoma. Virchows Arch. doi: 10.1007/s00428-014- 1692-5

Cai, C., He, H.H., Gao, S., Chen, S., Yu, Z., Gao, Y., Chen, S., Chen, M.W., Zhang, J., Ahmed. A., Wang, Y., Metzger, E., Schüle, R., X. Liu, X.S., Myles Brown, M. and Steven P. Balk, S.P. (2014) Lysine Specific Demethylase 1 has Dual Functions as a Major Regulator of Androgen Receptor Transcriptional Activity. Cell Rep. doi: 10.1016/j.celrep.2014.11.008

Pohlkamp, T., Steller, L., May, P., Guenther, T., Schüle, R., Frotscher, M., Herz, J. and Bock, H.H. (2014) Generation and Characterization of an Nse-CreERT2 Transgenic Line Suitable for Inducible Gene Manipulation in Cerebellar Granule Cells. PLoS One 9(6): e100384. doi:10.1371/journal.pone.0100384

Ray SK, Li HJ, Metzger M, Schüle R. and Leiter AB (2014) CtBP and associated LSD1 are required for transcriptional activation by NeuroD1 in gastrointestinal endocrine cells. Mol Cell Biol. 34, 2308-2317.

Heyne, K., Förster, J., Schüle, R. and Roemer. K. (2014) Transcriptional repressor NIR interacts with the p53-inhibiting ubiquitin ligase MDM2. Nucleic Acids Res. 42, 3565-3579.

Slynko, I., Scharfe, M., Rumpf, T., Eib, J., Metzger, E., Schüle, R., Jung, M. and Sippl, W. (2014) Virtual Screening of PRK1 Inhibitors: Ensemble Docking, RescoringUsing Binding Free Energy Calculation and QSAR Model Development. J. Chem. Inf. Model 54, 138-150.

Lucas, X., Wohlwend, D., Hügle, M., Schmidtkunz, K., Gerhardt, S., Schüle, R., Jung, M., Einsle, O. and Günther, S. (2013) 4-acyl pyrroles: Mimicking acetylated lysines in histone code reading. Angew Chem Int Ed Engl. 52, 14055-14059.

Schmitt, M.L., Hauser, A.T., Carlino, L., Pippel, M., Schulz-Fincke, J., Metzger, E., Willmann, D., Yiu, T., Barton, M., Schüle, R., Sippl, W. and Jung, M. (2013) Nonpeptidic propargylamines as inhibitors of lysine specific demethylase 1 (LSD1) with cellular activity. J Med Chem. 56, 7334-7342.

Brun, J., Dieudonné, F.X., Marty, C., Müller, J., Schüle, R., Patiño-García, A., Lecanda, F., Fromigué, O. and Marie, P.J. (2013) FHL2 silencing reduces Wnt signaling and osteosarcoma tumorigenesis in vitro and in vivo. PLoS One 8(1):e55034. Epub 2013 Jan 28.

Sprüssel, A., Schulte, J.H., Weber, S., Necke, M., Händschke, K., Thor, T., Pajtler, K.W.,Schramm, A., König, K., Diehl, L., Mestdagh, P., Vandesompele, J., Speleman, F., Jastrow, H., Heukamp, L.C., Schüle, R., Dührsen, U., Buettner, R., Eggert, A. and Göthert, J.R. (2012) Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation. Leukemia 26, 2039-2051.

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Prof. Dr. Christoph Peters
Tumorzentrum Freiburg CCCF
Phone: +49-761-270-71500
Hugstetter Str. 49
79106 Freiburg

and

Institute of Molecular Medicine and Cell Research
University of Freiburg
Stefan-Meier-Str. 17
79104 Freiburg
Phone: +49-761-203-9600/9601
christoph.peters@mol-med.uni-freiburg.de​​

Dr. Anja Hernández
Deutsches Krebsforschungszentrum (DKFZ)
Im Neuheimer Feld 280
69120 Heidelberg
++49 (0)761 270 22810
anja.hernandez@dkfz-heidelberg.de

Dr. Anna Dost
Deutsches Krebsforschungszentrum (DKFZ)
Im Neuheimer Feld 280
69120 Heidelberg
+49 (0)761 270 77121
a.dost@dkfz-heidelberg.de