Zentrum für Neuropathologie und Prionforschung
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Research Group Dr. Ulrich Schüller

(Developmental Neurobiology/Pediatric Neurooncology)flag_de_text

From May 1st 2016, the group will be located at the University Medical Center Hamburg Eppendorf and will be reached at:

The Schüller lab
University Medical Center Hamburg-Eppendorf
Research Institute Children's Cancer Center
Martinistrasse 52, Gebäude N63, D-20251 Hamburg, Germany
Phone: ++49-40-426051240
E-Mail: u.schueller@uke.de

Further Information will be available soon under http://www.kinderkrebs-forschung.de/ 

Research summary:

The group is interested in basic questions of neurodevelopmental biology as well as in questions of pediatric brain tumor formation, i.e. medulloblastoma. Medulloblastoma is a malignant tumor of the cerebellum which predominantly occurs in childhood. Causal therapy options are not yet available, but research efforts within the last decade have made substantial progress in discovering deregulations of highly conserved signalling pathways as causes for medulloblastoma development. In this context, the Schüller group is particularly interested in both the Sonic Hedghog and the Wnt/ß-catenin signaling pathways. We believe that understanding these signaling cascades during normal cerebellar development will be basic in order to fully understand processes that result in tumorigenesis.

Our aims are to
1.   understand the role of Sonic hedgehog and Wnt signaling in distinct cellular compartment of the brain
2.    anatomically and molecularly characterize tumor-initiating cells of ebryonal brain tumors
3.    identify essential regulators during the development of medulloblastoma
4.    identify novel biomarkers for dianostic pruposes in medulloblastoma
6.    identify novel targets for specific medulloblastoma treatments and test candidate drugs in preclinical mouse models

To achieve these goals we have established a biobank with more than 200 samples of human medulloblastoma (snap-frozen and/or formalin-fixed, paraffin-embedded as tissue microarray) including well documented clinical follow-up. We further culture a number of immortalized human medulloblastoma cell lines and work with conditional knockout mouse systems including novel medulloblastoma mouse models that we previously established (Schüller et al., Cancer Cell 2008; Grammel et al., Acta Neuropathol 2012). Our laboratory applies standard techniques of molecular biology (gene expression analysis using LightCycler, Luciferase assays, Sequencing, Western blotting, FACS analysis), histology (conventional stainings, immunohistochemistry, in situ hybridization) as well as methods of cell biology (primary culture of cerebellar granuel neuron precusors, proliferation assays, lentiviral-based knockdown assays, etc.)

Our work is done in close collaboration with multiple research institutions in Germany as well as with groups at the Harvard University (Dana-Farber Cancer Insitute) in Boston, USA, and the University of California San Francisco (UCSF), USA.

Selected recent publications:

1. Pöschl J., Bartels M., Ohli J., Bianchi E., Kuteykin-Teplyakov K., Grammel D., Ahlfeld J., Schüller U. (2014) Wnt/β-catenin signaling inhibits the Shh pathway and impairs tumor growth in Shh-dependent medulloblastoma. Acta Neuropathol, 127(4):605–607

2. Kool M., Jones D., Jäger N., Northcott P., Pugh T., Hovestadt V., Piro R., Esparza L., Markant S., Remke M., Milde T., Bourdeaut F., Rizhova M., Sturm D., Pfaff E., Stark S., Hutter S., Seker-Cin H., Johann P., Bender S., Schmidt S., Rausch T., Shih D., Reimand J., Sieber L., Wittmann A., Linke L., Weber U., Zapatka M., van Sluis P., Volckmann R., Koster J., Versteeg R., Schmdit S., Wolf S., Lawerenz C., Bartholomae C., von Kalle C., Unterberg A., Herold-Mende C., Hofer S., Kulozik A., von Deimling A., Scheurlen W., Felsberg J., Reifenberger G., Hasselblatt M., Crawford J., Grant G., Jabado N., Perry A., Cowdrey C., Croul C., Zadeh G., Korbel J., Doz F, Delattre O, Bader G., McCabe M., Collins P., Kieran M., Cho Y., Pomeroy S., Witt O., Brors B., Taylor M., Schüller U., Korshunov A., Eils R., Wechsler-Reya R., Lichter P., & Pfister S (2014) Genome Sequencing of SHH Medulloblastoma Predicts Genotype-Related Response to Smoothened-Inhibition. Cancer Cell, 25:393–405

3. Wefers A., Warmuth-Metz M., Pöschl J., von Bueren A., Monoranu C., Seelos K., Peraud A., Tonn J., Koch A., Pietsch T., Herold-Mende C., Mawrin C., Schouten-van Meeteren A., van Vuurden D., von Hoff K., Rutkowski S., Pfister S., Kool M., Schüller U. (2014) Subgroup-specific localization of human medulloblastoma based on pre-operative MRI. Acta Neuropathol, 127(6): 931-33.

4. Shih D., Northcott P., Remke M., Korshunov A., Ramaswamy V, Kool M., Luu B, Yao Y, Wang X, Dubuc A., Garzia L, Peacock J, Mack S, Wu X, Rolider A, Morrisy S, Cavalli F, Zitterbart K., Faria C., Schüller U., Kren L, Kumabe T., Tominaga T, Ra Y, Garami M, Hauser P., Chan J, Robinson S, Bognar L, Klekner A, Saad A, Liau L., Albrecht S, Fontebasso A., Cinalli G, Iolascon A, Zollo M, Cooper M, Thompson R, Bailey S, Lindsey J, Di Rocco C, Massimi L., Michiels E, Scherer C, Gupta N, Fan X, Muraszko K, Vikhabar R, Eberhart C., Fouladi M, Lach B, Jung S., Wechsler-Reya R, Fevre-Montagne M., Jouvet A., Jabado N., Pollack I., Weiss W., Cho B, Kim S, Wang K., Leonard J., Rubin J., de Torres C, Lavarino C, Mora J, Cho J., Tabori U., Olson J, Gajjar A, Packer R., Rutkowski S., Pomeroy S., French P, Kloosterhof N, Kros J, von Meir E., Clifford S, Delattre O, Doz F, Reynaud S, Hawkins C., Maliin D, Grabjkowska W., Perke-Polnik M, Bouffet E., Rutka J, Pfister S, & Taylor M. (2014) Cytogenetic Prognostication within Medulloblastoma Subgroups. J Clin Oncol, 32(9):886-96.

5. Pöschl J., Stark S., Neumann P., Gröbner S., Kawauchi D., Jones D., Northcott P., Lichter P., Pfister S., Kool M., Schüller U. (2014) Genomic and transcriptomic analyses match medulloblastoma mouse models to their human counterparts. Acta Neuropathol, 128(1):123-36.

6. Moreno N., Schmidt C., Ahlfeld J., Pöschl J., Dittmar S., Pfister S., Kool M., Kerl K., Schüller U. (2014) Loss of Smarc proteins impairs cerebellar development. J Neurosci, 34(40):13486 –13491.

7. Pöschl J., Koch A., Schüller U. (2015) Histological subtype of medulloblastoma frequently changes upon recurrence. Acta Neuropathol, 129(3):459-61.

8. Ohli J., Neumann J., Grammel D., Schüller U. (2015) Localization of SHH medulloblastoma in mice depends on the age at its initiation. Acta Neuropathol, 130(2):307-9.

9. Morrissy S., Garzia L., Shih D., Zuyderduyn S., Huang X., Skowron P., Remke M., Cavalli F., Ramaswamy V., Lindsay P., Jelveh S., Donovan L, Wang X., Luu B., Zayne K., Li Y., Mungall K., Mayoh C., Thiessen N., Mercier E., Ma Y., Tse K., Zeng T., Shumansky K., Roth A., Shah S., Farooq H., Holgado B., Lee J., Matan-Lithwick S., Qin L., Reimand J., Rolider A., Liu J., Thompson Y., Wu X., Mack S., Manno A., Michealraj K., Nor C., Peacock J., Pugh T., Ally A., Bilenky M., Butterfield Y., Carlsen R., Cheng Y., Li H., Long W., Mayo M., Plettner P., Qian J., Schein J., Tam A., Wong T., Birol I., Zhao Y., Chuah E., Corbett R., Dhalla N., He A., Lee D., Faria C., Pimentel J., Nunes S., Shalaby T., Grotzer M., Pollack I., Hamilton R., Li X., Bendel A., Fults D., Walter A., Kumabe T., Tominaga T., Collins V., Cho Y., Hoffman C., Lyden D., Wisoff J., Garvin J. , Stearns D., Massimi L., Schüller U., Sterba J., Zitterbart K., Puget S., Ayrault O., Dunn S., Tirapelli D., Carlotti C., Wheeler H., Hallahan A., Ingram W., MacDonald T., Olson J., Van Meir E., Lee J., Wang K., Kim S., Cho B., Pietsch T., Fleischhack G., Tippelt S., Ra Y., Bailey S., Clifford S., Lindsey J., Eberhart C., Cooper M., Packer R., Mas-simino M., Garre M., Bartels U., Tabori U., Hawkins C., Dirks P., Rutka J., Bouffet E., Wechsler-Reya R., Weiss W., Collier L., Dupuy A., Korshunov A., Jones D., Kool M., North-cott P., Pfister S., Largaespada A., Mungall A., Moore R., Jabadao N., Bader G., Jones S., Malkin D., Marra M., Taylor M. (2016) Divergent Clonal Selection Dominates Medulloblastoma at Recurrence. Nature, 529:351-357.

10. Johann P., Erkek S., Zapatka M., Kerl K., Buchhalter I., Hovestadt V., Jones D., Sturm D., Hermann C., Wang M., Korshunov A., Rhyzova M., Gröbner S., Brabetz S., Chavez L., Bens S., Gröschel S., Kratochwil F., Wittmann A., Sieber L., Geörg C., Wolf S., Beck K., Oyen F., Capper D., van Sluis P., Volckmann R., Koster J., Versteeg R., von Deimling A., Milde T., Witt O., Kulozik A., Ebinger M., Shalaby T., Grotzer M., Sumerauer D., Mora J., Jabado N., Taylor M., Huang A., Aronica E., Bertoni A., Radlwimmer B., Pietsch T., Schüller U., Schneppen-heim R., Northcott P., Siebert R., Frühwald M., Lichter P., Eils R., Gajjar A., Hasselblatt M., Pfister S., Kool M. Atypical teratoid/rhabdoid tumor (ATRT) is an epigenetically heterogeneous disease with distinct subgroup specific enhancer landscapes. Cancer Cell, in press

 

A full list of publications is available here.

Funding:

Our work is generously supported by the Deutsche Krebshilfe, the Wilhelm Sander-Foundation, the Else-Kröner-Fresenius-Foundation, the Friedrich Baur-Foundation, the Georg und Traud Gravenhorst-Foundation and the Förderprogramm für Forschung und Lehre (FöFoLe, LMU Munich). If you would like to sponsor our research, please contact Dr. Schüller directly.