Division of Molecular Neurogenetics
Dr. Hai-Kun Liu
Neural stem cells (NSCs) are cells that can self-renew and differentiate into neuronal or glial cells. During development, NSCs are responsible to generate different type of neuronal and glial cells, which are the fundamental cellular unit for brain function. Recent discovery of adult NSCs provides solid evidence of adult neurogenesis in certain areas of mammalian brain. On the other hand, these cells have been suggested to be involved in many of human brain diseases, like brain tumors, depression and autism. Therefore adult NSCs were considered to be a good model system to investigate molecular mechanisms of human brain diseases in vivo. Glioblastoma multiforme (GBM, World Health Organization grade IV) is the most common primary brain tumor in adults. Patients with newly diagnosed GBM have a median survival of approximately 14 months irrespective of the therapeutic modalities and the tumors almost inevitably relapse. Recent studies suggested that a small subpopulation of tumor cells, the so-called brain tumor stem cells (BTSCs), are responsible for driving the growth of malignant gliomas. Interestingly, the BTSCs share many similarities with normal NSCs, in particular they use similar pathways to maintain their self-renewal capacity. In our lab, we are using mouse genetic tools to study molecular regulations of NSCs, BTSCs and other related neurological diseases.
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