Braun Lab
Max Eder Junior Research Group
Research topics
- Targeted therapy for childhood cancers
- Genome-wide genetic screens
- Role of RNA life cycle in cancer biology
- Personalized therapy of pediatric tumors
Dr. med. Christian J. Braun
✉ chr.braun@med.lmu.de
☎ +49-89-4400-54724
We are trying to understand what mechanisms are employed by childhood cancers to fuel their oncogenic signaling machinery. In order to do so, we employ state of the art model systems for pediatric tumors, high-throughput CRISPR and RNAi screens, comprehensive analyses of transcriptional landscapes as well as customized experimental pipelines for the establishment of biomarker profiles.
Our group is particularly interested in discovering and characterizing new targetable vulnerabilities to advance the therapy of pediatric nervous system tumors such as glioma and neuroblastoma.
All classes of cellular RNAs are subject to direct and post-transcriptional modification. RNA binding proteins (RBPs) specifically recognize many of these modifications and consecutively influence RNA stability, alternative splicing, location and decay. There is emerging evidence that both developing tissues and cancer cells utilize these ‘epitranscriptional’ processes to orchestrate gene expression profiles in a coordinated fashion (Braun and Hemann, Curr Opin Genet Dev, 2019).
Not surprisingly, core ‘epitranscriptional’ regulators such as splice factors are frequently subject to mutation in cancer. We have previously found that the splicing rate of specific introns contributes to gene expression orchestration in both physiology and cancer. Intriguingly, this process represents a targetable vulnerability (Braun et al., Cancer Cell, 2017).
Our lab is interested in deeper characterizing this observation and in systematically analyzing the role of post-transcriptional RNA biology in childhood cancer.
We are trying to understand what mechanisms are employed by childhood cancers to fuel their oncogenic signaling machinery. In order to do so, we employ state of the art model systems for pediatric tumors, high-throughput CRISPR and RNAi screens, comprehensive analyses of transcriptional landscapes as well as customized experimental pipelines for the establishment of biomarker profiles. We have successfully applied these experimental systems to several disease entities such as brain cancer, lymphoma and leukemia in the past.
Our group is particularly interested in discovering and characterizing new targetable vulnerabilities to advance the therapy of pediatric nervous system tumors such as glioma and neuroblastoma, but are also eager to collaborate on applying our screening technologies to biological questions far away from molecular oncology.
Many targeted cancer therapies fail in clinical trials – which is dilemma for patients, society and health care economy. In general, the effectiveness of targeted therapies tends to fall behind expectations when there is no stratifying biomarker available enabling clinicians to restrict treatment to sensitive sub-cohorts of patients. When characterizing novel therapeutic vulnerabilities, we therefore aim to systematically establish gene expression signatures predictive of therapeutic sensitivity
Dorothea Mock, Cand. med.
Doctoral Researcher (MD track)
✉ dorothea.mock@med.uni-muenchen.de
Room: K0.31
Heidi Noll-Puchta, VTA
Technician & Lab Manager
✉ Heidi.Noll-Puchta@med.uni-muenchen.de
☎ 089-4400-54724
Room: K0.31
Andres Carbonell Adames, M.Sc.
Doctoral Researcher (PhD track)
✉ Andres.Carbonell@med.uni-muenchen.de
☎ 089-4400-54724
Room: K0.31
Federica Furlanetto, M.Sc.
Doctoral Researcher (PhD track)
Co-advised with Roland Rad @ TU München
TranslaTUM, Einsteinstraße 25, Munich
Selected Publications
C. J. Braun*, M. Stanciu*, P. L. Boutz*, J. C. Patterson, D. Calligaris, F. Higuchi, R. Neupane, S. Fenoglio, D. P. Cahill, H. Wakimoto, N. Y. R. Agar, M. B. Yaffe, P. A. Sharp, M. T. Hemann, J. A. Lees, “Coordinated Splicing of Regulatory Detained Introns within Oncogenic Transcripts Creates an Exploitable Vulnerability in Malignant Glioma,” Cancer Cell, Oct 9 2017. 32(4):411-426.e11. Link
C. J. Braun*, P. M. Bruno*, M. A. Horlbeck, L. A. Gilbert, J. S. Weissman, M. T. Hemann, “Versatile in vivo regulation of tumor phenotypes by dCas9 mediated transcriptional perturbation,” PNAS, June 20 2016. Link
C. J. Braun*, K. Boztug*, A. Paruzynski*, M. Witzel*, A. Schwarzer, M. Rothe, U. Modlich, R. Beier, G. Göhring, D. Steinemann, R. Fronza, C. R. Ball, R. Haemmerle, S. Naundorf, K. Kühlcke, M. Rose, C. Fraser, L. Mathias, R. Ferrari, M. R. Abboud, W. Al-Herz, I. Kondratenko, L. Maródi, H. Glimm, B. Schlegelberger, A. Schambach, M. H. Albert, M. Schmidt, C. von Kalle, and C. Klein, “Gene therapy for wiskott-Aldrich syndrome--long-term efficacy and genotoxicity.,” Sci Transl Med, Mar. 2014. Link
C. P. Pallasch, I. Leskov, C. J. Braun, D. Vorholt, A. Drake, Y. M. Soto-Feliciano, E. H. Bent, J. Schwamb, B. Iliopoulou, N. Kutsch, N. van Rooijen, L. P. Frenzel, C. M. Wendtner, L. Heukamp, K. A. Kreuzer, M. Hallek, J. Chen, and M. T. Hemann, “Sensitizing Protective Tumor Microenvironments to Antibody-Mediated Therapy,” Cell, vol. 156, no. 3, pp. 590–602, Jan. 2014. Link
I. G. Cannell, K. A. Merrick*, S. Morandell*, C. Z. Zhu, C. J. Braun, R. A. Grant, E. R. Cameron, M. Tsao, M.T. Hemann and M. B. Yaffe. “A Pleiotropic RNA-Binding Protein Controls Distinct Cell Cycle Checkpoints to Drive Resistance of p53-defective Tumors to Chemotherapy,” Cancer Cell, 2015. Link
*equal contribution
CLUE: Multiplexed sgRNA library design and production
Pooled sgRNA libraries targeting hundreds or thousands of individual genes are right at the heart of functional genomics. Such libraries are broadly available, but usually not tailored to the scientific interest of researchers. With our tool CRISPR clue were were out to bring custom sgRNA library production to all labs - streamlining the cloning process, lowering synthesis costs and reducing bioinformatics to the bare minimum. Check out www.crispr-clue.de and the manuscript preprint available at biorxiv.org!
Dorothea, Christian, Heidi & Federica having fun at our Christmas party
Dorothea presenting about dCas9 and transcriptional road blocks at Kubus Science Fair
Christian Braun Lab
Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital,
Klinikum der Universität München, LMU München
Postal Address: Lindwurmstr. 4
Visiting Address: Research Building, Lindwurmstraße 2a
80337 Munich
Germany
Room: K 0.5
Phone: +49 (0)89 - 4400 - 54724
Fax: +49 (0)89 - 4400 - 57702
Email: chr.braun@med.lmu.de
Lab Manager: Heidi Noll-Puchta
Postal Address: Lindwurmstr. 4
Visiting Address: Research Building, Lindwurmstraße 2a
80337 Munich
Germany
Room: K 0.31
Phone: +49 (0)89 - 4400 - 54724
Fax: +49 (0)89 - 4400 - 57702
Email: Heidi.Noll-Puchta@med.uni-muenchen.de