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Translational Cancer Research
Applied Functional Genomics

Research

Division of Applied Functional Genomics

Prof. Dr. Claudia Scholl

Multicolor immunofluorescence staining of different mouse lung epithelial cells
© dkfz.de

During malignant transformation, somatically acquired genetic alterations result in complex quantitative and qualitative changes in intracellular signaling pathways. Functional genomic analyses have the potential to uncover essential components of these deregulated pathways that can represent tumor-specific vulnerabilities. The overall aim of our research is to identify such molecular and functional abnormalities in human cancer cells, with particular focus on alterations that can be exploited to design better therapeutic strategies. To achieve this goal, we use a broad spectrum of molecular and cell biological technologies, such as RNA interference or CRISPR/Cas9-mediated genome editing on small and large scale and in combination with diverse phenotypic readouts. Projects that are currently pursued include:

  • Identification of novel signaling pathways that are essential for the transforming activity of mutant KRAS, the most frequently mutated oncogene in human cancers, by using proteomic and functional genomic tools with the aim to identify potentially druggable “Achilles’ heels” in KRAS mutant cancer cells
  • Characterization of the physiological and oncogenic function of STK33, an uncharacterized serine/threonine kinase that is essential for the survival of mutant KRAS-dependent cancer cells
  • Identification of normal and malignant lung epithelial stem cells and delineation of regulatory pathways within these cell types using genetically engineered mouse models (see also SFB 873)
  • Identification and characterization of context-dependent functional vulnerabilities in acute myeloid leukemia and soft-tissue sarcoma (in collaboration with the group of Prof. Stefan Fröhling, NCT Heidelberg)

Furthermore, we are currently building a platform for the rapid functional characterization of altered genes in cancer genomes, complementing translationally oriented cancer sequencing efforts. This approach will allow the systematic discrimination between pathogenetically relevant driver mutations and biologically neutral passenger alterations.

Contact

Prof. Dr. Claudia Scholl
Applied Functional Genomics (G102)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 581
69120 Heidelberg
Tel: +49 6221 42 1636

Selected Publications

  • 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. (2009). Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells. Cell,137, 821-34. *Equal conribution.
  • 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.* (2012). Targeting of KRAS mutant tumors by HSP90 inhibitors involves degradation of STK33. J Exp Med, 209, 697-711. *Equal conribution.
  • 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.* (2013). CDX2-driven leukemogenesis involves KLF4 repression and deregulated PPAR? signaling. J Clin Invest, 123, 299-314. *Equal conribution.
  • 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.* (2014). Requirement for CDK6 in MLL-rearranged acute myeloid leukemia. Blood, 124, 13-23. *Equal conribution.
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