AG Büchel
Prof. Dr. Gabriele Büchel
Professur für Dynamik zellulärer Proteinkomplexe
Lehrstuhl für Biochemie und Molekularbiologie
Biozentrum
Am Hubland
97074 Würzburg
Raum B311
Tel: 0931 31 84946
Fax: 0931 31 84113
gabriele.buechel@uni-wuerzburg.de
https://www.uni-wuerzburg.de/aktuelles/einblick/single/news/juniorprofessur-in-der-krebsforschung/
https://www.uni-due.de/zmb/medbio-absolventin-juniorprofessorin.php
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
Dehmer M.*, Trunk K.*, ..., Eilers M., Büchel G. (2025). USP11/TCEAL1 complex promotes transcription elongation to sustain oncogenic gene expression in neuroblastoma. Genes Dev. https://doi.org/10.1101/gad.352166.124, PMID: 40250979
Vidal, R., ..., Büchel, G. (2024). Association with TFIIIC limits MYCN localisation in hubs of active promoters and chromatin accumulation of non-phosphorylated RNA polymerase II. Elife, 13. https://doi.org/10.7554/eLife.94407, PMID: 39177021
Papadopoulos, D., Ha, S. A., Fleischhauer, D., ..., Büchel, G., Vos, S. M., & Eilers, M. (2024). The MYCN oncoprotein is an RNA-binding accessory factor of the nuclear exosome targeting complex. Mol Cell, 84(11), 2070-2086 e2020. https://doi.org/10.1016/j.molcel.2024.04.007, PMID: 38703770
Roeschert I, …, Chesler L, Büchel G* and Eilers M* (2021) Combined inhibition of Aurora-A and ATR kinases results in regression of MYCN-amplified neuroblastoma. Nature Cancer, 2021. doi: 10.1038/s43018-020-00171-8, PMID: 33768209. *joint senior authors
Wolpaw, A. J., Bayliss, R., Büchel, G., …, Mosse, Y. P. (2021). Drugging the "Undruggable" MYCN Oncogenic Transcription Factor: Overcoming Previous Obstacles to Impact Childhood Cancers. Cancer Res 81, 1627-1632. doi: 10.1158/0008-5472.CAN-20-3108. PMID: 33509943.
Herold, S.*, Kalb, J. *, Büchel, G. *, …, Eilers, M. (2019). Recruitment of BRCA1 limits MYCN-driven accumulation of stalled RNA polymerase. Nature 567, 545-549. doi: 10.1038/s41586-019-1030-9. PMID: 30894746 *Joint first authors
Büchel, G., Carstensen, A., Mak, K.Y., …, Eilers, M. (2017). Association with Aurora-A Controls N-MYC-Dependent Promoter Escape and Pause Release of RNA Polymerase II during the Cell Cycle. Cell Rep 21, 3483-3497. doi: 10.1016/j.celrep.2017.11.090. PMID: 29262328.
