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Division of Molecular Embryology

Prof. Dr. Christof Niehrs

Multiciliated cells of Xenopus embryos
© dkfz.de

How cells communicate with their environment via cell-cell interactions and by growth factors is a key question in the molecular life sciences, including tumor biology. Wnt signaling plays an important role in embryonic development and cancer. In the Division of Molecular Embryology we study mechanisms of Wnt pathway regulation. To this end, we identify developmental control genes, investigate what their biological role and biochemical mode of action is, and how the genes are regulated. Our particular interest is to investigate signal transduction of Wnt receptors and associated cofactors, notably R-spondins, a class of secreted Wnt agonists. Moreover, we investigate the role of DEAD box RNA helicases as a novel class of protein kinase regulators in Wnt signaling and beyond.

As experimental model systems, we use mouse and frog embryos as well as organoid- and mammalian cell culture and we make use of innovative molecular technologies for their analysis. Thus, we follow a comprehensive approach spanning from the biochemical to the organismic level, to unravel the Wnt signaling network and its biological role, as a basis for novel translational approaches in tumor biology.

Future Outlook
We currently pursue four main lines of research. (1) We described that all cilia classes (flagella, primary cilia, multi-cilia) are Wnt-signaling organelles and we currently investigate the physiological importance of this signaling in mouse physiology. (2) We showed that DEAD box RNA helicases (DDX proteins) are a new class of regulators of protein kinases. We investigate the mechanism of action, notably in protein condensates during Wnt signaling and the biological role of the DDX-kinase interactions. (3) We study the role and biochemical mechanism of action of R-spondins, a class of Wnt agonist that play an important role in development as well as oncogenes and tumor suppressors. (4) We develop ROTACs as a novel class of protein targeting chimeras in cancer therapy.

Contact

Prof. Dr. Christof Niehrs
Molecular Embryology (A050)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 4693

Selected Publications

  • Koch, S. et al. (2015). Post-transcriptional Wnt Signaling Governs Epididymal Sperm Maturation. Cell, 163(5),1225-1236
  • Huang, Y.L. et al. (2014). Polarized Wnt Signaling Regulates Ectodermal Cell Fate in Xenopus. Dev Cell, 29(10), 250-257.
  • Cruciat, C.M. et al. (2013). RNA helicase DDX3 is a regulatory subunit of casein kinase 1 in Wnt-?-catenin signaling. Science, 339(6126), 1436-1441.
  • Niehrs, C. (2012). The complex world of WNT receptor signalling. Nat. Rev. Mol. Cell Biol. 13(494), 767-779.
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