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    Chair of Biochemistry and Molecular Biology

    AG Büchel

    Dr. Gabriele Büchel

    Lehrstuhl für Biochemie und Molekularbiologie
    Biozentrum
    Am Hubland
    97074 Würzburg
    Raum B351

    Tel: 0931 31 84946
    Fax: 0931 31 84113

    gabriele.buechel@uni-wuerzburg.de

    Research

    Protein-dynamic of MYC/MYCN complexes

    MYC proteins interact with a variety of other proteins. Those interaction partners play a role in diverse processes. Therefore, by changing interaction partners MYC can regulate different processes. The aim of our studies is to investigate the protein dynamic of MYC complexes, identify vulnerabilities and exploit it for therapy.

    Targeting transcription-replication conflicts in MYCN-driven neuroblastoma

    MYC proteins are transcription factors that bind to active promoters and promote transcriptional elongation. In neuroblastoma, a solid tumor in childhood, expression of MYCN is deregulated in high risk patients. Despite multimodal therapies the outcome of those patients is very poor showing the urgent need for new therapy options.
    We could show already that MYC-driven tumors are dependent on Aurora-A and a sensitive to Aurora-A inhibitors. Those inhibitors entered already clinical trials but they have a lot of side effects and patients eventually relapse. We want to exploit combination therapies with Aurora-A inhibitors. Understanding the mechanisms how combination therapy is affecting the tumor will show new and specific vulnerabilities for improving therapy of neuroblastoma.

    Publications

    2021

    Roeschert, I., Poon, E., Henssen, A.G., Dorado Garcia, H., Gatti, M., Giansanti, C., Jamin, Y., Ade, C.P., Gallant, P., Schülein-Völk, C., Beli, P., Richards, M., Rosenfeldt, M., Altmeyer, M., Anderson, J., Eggert, A., Dobbelstein, M., Bayliss, R., Chesler, L.*, Büchel, G.*, and Eilers, M.*, Combined inhibition of Aurora-A and ATR kinases results in regression of MYCN-amplified neuroblastoma. Nat Cancer (2021). https://doi.org/10.1038/s43018-020-00171-8

    Wolpaw AJ, Bayliss R, Büchel G, Dang CV, Eilers M, Gustafson WC, Hansen GM, Jura N, Knapp S, Lemmon MA, Levens D, Maris JM, Marmorstein R, Metallo SJ, Park JR, Penn LZ, Rape M, Roussel MF, Shokat KM, Tansey WP, Verba KA, Vos SM, Weiss WA, Wolf E, Mossé YP, Drugging the 'undruggable' MYCN oncogenic transcription factor: Overcoming previous obstacles to impact childhood cancers. Cancer Res. 2021 Jan 28:canres.3108.2020. doi: 10.1158/0008-5472.CAN-20-3108. Review.

    2019

    Herold, S.*, Kalb, J.*, Büchel, G.*, Ade, C. P., Baluapuri, A., Xu, J., Koster, J., Solvie, D., Carstensen, A., Klotz, C., Rodewald, S., Schülein-Volk, C., Dobbelstein, M., Wolf, E., Molenaar, J., Versteeg, R., Walz, S., Eilers, M. (2019). Recruitment of BRCA1 limits MYCN-driven accumulation of stalled RNA Polymerase. Nature. 2019 Mar;567(7749):545-549. doi: 10.1038/s41586-019-1030-9, * joint first author

    2018

    Batzke K, Büchel G, Hansen W, Schramm A, TrkB-Target Galectin-1 Impairs Immune Activation and Radiation Responses in Neuroblastoma: Implications for Tumour Therapy. .Int J Mol Sci. 2018 Mar 2;19(3):718. doi: 10.3390/ijms19030718.PMID: 29498681

    2017

    Büchel, G., Carstensen, A., Mak, K.Y., Roeschert, I., Leen, E., Sumara, O., Hofstetter, J., Herold, S., Kalb, J., Baluapuri, A., Poon, E., Kwok, C., Chesler, L., Maric H. M., Rickman, D. S., Wolf, E., Bayliss, R., Walz, S., Eilers, M. (2017) Association with Aurora-A controls N-MYC-dependent promoter escape and pause release of RNA polymerase II during cell cycle. Cell Reports Dec 19;21(12):3483-3497. doi:10.1016/j.celrep.2017.11.090.

    2016

    Büchel G, Schulte JH, Harrison L, Batzke K, Schüller U, Hansen W, Schramm A , Immune response modulation by Galectin-1 in a transgenic model of neuroblastoma. Oncoimmunology. 2016 Feb 18;5(5):e1131378. doi: 10.1080/2162402X.2015.1131378. eCollection 2016 May.PMID: 27467948

    2013

    Schramm A, Köster J, Marschall T, Martin M, Schwermer M, Fielitz K, Büchel G, Barann M, Esser D, Rosenstiel P, Rahmann S, Eggert A, Schulte JH. Next-generation RNA sequencing reveals differential expression of MYCN target genes and suggests the mTOR pathway as a promising therapy target in MYCN-amplified neuroblastoma. Int J Cancer. 2013 Feb 1;132(3):E106-15. doi: 10.1002/ijc.27787.