- Uras IZ, Walter GJ, Scheicher R, Bellutti F, Prchal-Murphy M, Tigan AS, Valent P, Heidel FH, Kubicek S, Scholl C, Fröhling S, Sexl V. Palbociclib treatment of FLT3-ITD+ AML cells uncovers a kinase-dependent transcriptional regulation of FLT3 and PIM1 by CDK6. Blood 127:2890-902, 2016
- Stolze B, Reinhart S, Bulllinger L, Fröhling S, Scholl C. Comparative analysis of KRAS codon 12, 13, 18, 61, and 117 mutations using human MCF10A isogenic cell lines. Sci Rep 5:8535, 2015.
- Azoitei N, Diepold K, Brunner C, Rouhi A, Genze F, Becher A, Kestler H, van Lint J, Chiosis G, Koren J 3rd, Fröhling S, Scholl C, Seufferlein T. HSP90 supports tumor growth and angiogenesis through PRKD2 protein stabilization. Cancer Res 74:7125-7136, 2014.
- Placke T, Faber K, Nonami A, Putwain SL, Salih HR, Heidel FH, Krämer A, Root DE, Barbie DA, Krivtsov AV, Armstrong SA, Hahn WC, Huntly BJ, Sykes SM, Milsom MD, Scholl C,* Fröhling S.* Requirement for CDK6 in MLL-rearranged acute myeloid leukemia. Blood 124:13-23, 2014. *Equal contribution.
- Faber K, Bullinger L, Ragu C, Garding A, Mertens D, Miller C, Martin D, Walcher D, Döhner K, Döhner H, Claus R, Plass C, Sykes SM, Lane SW, Scholl C,* Fröhling S.* CDX2-driven leukemogenesis involves KLF4 repression and deregulated PPARγ signaling. J Clin Invest 123:299-314, 2013. *Equal contribution.
- Azoitei N, Hoffmann CM, Ellegast JM, Ball CR, Obermayer K, Gößele U, Koch B, Faber K, Genze F, Schrader M, Kestler HA, Döhner H, Chiosis G, Glimm H, Fröhling S,* Scholl C.* Targeting of KRAS mutant tumors by HSP90 inhibitors involves degradation of STK33. J Exp Med 209:697-711, 2012. *Equal contribution.
- Sykes SM, Lane SW, Bullinger L, Kalaitzidis D, Yusuf R, Saez B, Ferraro F, Mercier F, Singh H, Brumme KM, Acharya SA, Scholl C, Tothova Z, Attar E, Fröhling S, DePinho RA, Gilliland DG, Armstrong SA, Scadden DT. AKT/FOXO signaling enforces reversible differentiation blockade in myeloid leukemias. Cell 146:697-708, 2011.
- Scholl C,* Fröhling S,* Dunn IF, Schinzel AC, Barbie DA, Kim SY, Silver SJ, Tamayo P, Wadlow RC, Ramaswamy S, Döhner K, Bullinger L, Sandy P, Boehm JS, Root DE, Jacks T, Hahn WC, Gilliland DG. Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells. Cell 137:821-834, 2009. *Equal contribution.
To Find and Elucidate...
Druggable Vulnerabilities in Cancer Cells.
One main focus of our laboratory is the identification of signaling pathways that are essential for the transforming activity of mutant KRAS, the most frequently mutated oncogene in human cancer. Specifically, we are using technologies such as proteomic and functional genomic screens to uncover potentially druggable “Achilles’ heels” in KRAS mutant cancer cells.
In addition, we are investigating the physiological and oncogenic function of STK33, an uncharacterized serine/threonine kinase that is essential for the survival of mutant KRAS-dependent cancer cells.
This research area focuses on the identification of normal and malignant lung epithelial stem cells and the delineation of regulatory pathways within these cell types using genetically engineered mouse models. (Upper picture: adapted from Rock and Hogan, Annu Rev Cell Dev Biol 2011)
In close collaboration with the group of Prof. Stefan Fröhling (NCT Heidelberg), we are working on the identification and characterization of context-dependent functional vulnerabilities in acute myeloid leukemia and soft-tissue sarcoma, with the goal to better understand the biology of these mesenchymal malignancies and to use this knowledge for the development of targeted therapies. For example, we employ large-scale functional screening using short hairpin RNA or CRISPR/Cas9 libraries, followed by detailed validation experiments.
In close collaboration with the research groups of Michael Boutros (DKFZ), Ingrid Lohmann (Heidelberg University), Stefan Fröhling (NCT, Heidelberg University Hospital), Wolfgang Huber (EMBL), and Benedikt Brors (DKFZ), we are currently implementing a novel scientific program for the systematic functional annotation of cancer gene mutations and their interaction networks (SyNC). Through this project, we will gain insight into the mechanisms and interactions of cancer genes, thereby allowing the interpretation of cancer genomes and helping investigators to guide the translation of genetic lesions into clinical application. This initiative complements ongoing cancer genome efforts at DKFZ and NCT. We plan to provide our results to the scientific community through a newly designed public data resource, and implemented a biannual conference on Cancer Systems Genetics to foster scientific exchange.
On the Cover: FLT3 Drivers and Passengers on the Road to Leukemia (Fröhling & Scholl et al., Cancer Cell 2007)
On the Cover: Uncovering an Achilles’ Heel in Cancer (Scholl & Fröhling et al., Cell 2009)
Ph.D. and postdoc opportunities
If you are interested in joining our research team, please send an email to the group leader including full CV, statement of interest, certificates and references.
Lea Jopp-Saile (Student Assistant)
Simon Weisemann (Medical Thesis)