Division of Molecular Neurogenetics

Dr. Hai-Kun Liu

A newborn neuron (green) in hippocampus (DAPI in blue).
© dkfz.de

Active adult neurogenesis is one of the most exciting discoveries in neuroscience within the last decade. The subventricular zone (SVZ) of the lateral ventricle (LV) and the subgranular zone (SGZ) of the dentate gyrus (DG) in the hippocampus are the largest germinal zones of sustained neurogenesis during adulthood in the mammalian central nervous system. Astrocyte-like type B cells in the adult SVZ are thought to be multipotent neural stem cells (NSCs). These cells give rise to transient amplifying type C cells, which in turn differentiate into type A cells (neuroblasts) that migrate to the olfactory bulb (OB) through the rostral migratory stream (RMS). NSCs in the SGZ mainly give rise to new granular cells in the DG which are thought to be important for spatial learning and memory. Adult neurogenesis in the SVZ represents a unique system in which to study regulation of NSC proliferation, differentiation and directed neuronal migration in vivo. Strikingly, these cells can also initiate gliomagenesis after acquiring the same oncogenic mutations which were found in human brain tumor patients. Our lab aims to identify crucial molecular pathways that are important for the regulation of normal and neoplastic neural stem cells. To achieve this goal, we are mainly using mouse models in which we have altered the activity of some oncogenes, tumor suppressors and chromatin remodelers specifically in adult mouse neural stem cells.

We have generated several mouse models which can be used to introduce genetic mutations specifically in NSCs. We are currently using these models to study:

    1. Genetic and epigenetic regulation of neural stem cells: Epigenetic mechanisms are crucial for the regulation of the most important characteristics of stem cells, namely, self-renewal and multipotency. Key transcriptional factors play decisive roles in determining the identity of stem cells and their progenies. One major focus in our lab is understanding the interplay between crucial transcriptional factor and chromatin remodelers, in particular their functions during neural stem cell self-renewal and differentiation.
    2. Neoplastic neural stem cells: One important issue of targeting brain tumor stem cells (BTSCs) is to avoid damaging normal stem cells. Thus our goal is to identify critical differences between normal and tumor stem cells, which will provide important information for targeting BTSCs exclusively.
    3. Mouse models of brain tumors: We have developed several inducible mouse brain tumor models by introducing genetic mutations that are frequently found in human patients. We consider the inducible model a better model to recapitulate human glioblastoma, and it will be extremely interesting to further investigate the cellular and molecular changes that occur before detectable brain tumor formation in this particular model.


Dr. Hai-Kun Liu
Molecular Neurogenetics (A240)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 581
69120 Heidelberg
Tel: +49 6221 42 3266

Selected Publications

  • Liu, H-K., Wang, Y., Belz, T., Bock, D., Takacs, A., Radlwimmer, B., Barbus, S., Reifenberger, G., Lichter, P., Schütz, G. (2010). The nuclear receptor tailless induces long-term neural stem cell expansion and brain tumor initiation. Genes Dev 24:683-695
  • Liu H-K., Belz T., Bock D., Takacs A., Wu H., Lichter P., Chai M-Q., Schütz G. (2008) The nuclear receptor Tailless is required for neurogenesis in the adult subventricular zone, Genes Dev 22:2473-2478
  • Zhu, Z., Kahn, A., Weiler, M., Blaes. J, Jestaedt L., Geibert M., Zou P., Gronych J., Bernhardt, O., Korshunov, A., Bugner, V., Lichter, P., Radlwimmer, B., Heiland S., Bendszus, M., Wick, W., Liu, H-K*. (2014) Targeting self-renewal in high-grade brain tumors leads to loss of brain tumor stem cells and prolonged survival. Cell Stem Cell, DOI: 10.1016/j.stem.2014.04.007
  • Feng, W., Kahn, A., Bellvis P., Zhu, Z., Bernhardt, O., Herold-Mende, C., Liu, H-K*. (2013). The chromatin remodeler CHD7 regulates adult neurogenesis via activation of SoxC transcription factors. Cell Stem Cell, 13, 62–72
to top