The central goal of our research is to understand the molecular mechanisms of neural stem cell differentiation and neural regeneration in the central nervous system. We are particularly interested in gliogenesis, myelin formation, neural repair after injury and brain tumor (glioma) formation. Neuroglial cells (oligodendrocytes and astrocytes), consisting of more than 90 percent cells in our brain, play a very important role in establishment and maintenance of normal neuronal functions and formation of neurological diseases. Any brain functions, traditionally considered as the sole act of neurons, involve glial cells. Glial biology is emerging as a new frontier of current neuroscience, there is much to explore and re-explore. Using gliogenesis as a model system for neural stem cell differentiation, we have identified a number of regulatory genes important for the formation of neurons and glial cells in the CNS. We are currently utilizing multiple developmental and molecular genetic approaches to uncover the biological principles underlying the role of glial cells in brain formation and repair. Our study should contribute to clinical diagnosis and treatment of brain injuries, gliomas and neurological disorders.
Our current projects include: (1) Roles of Olig1 and Olig2 in brain development and regeneration (2)Transcriptional network in regulating oligodendrocyte myelination and remyelination after injury (3) Epigenetic control of gliogenesis (4) Functional modeling of neural-glial interaction (5) Glial dysfunction-mediated neuropathic disorders
RESEARCH INTERESTS
Neural stem cell biology
Oligodendrocyte myelination and repair
Gliogenesis and neuroregeneration
Glioma formation/glioma initiating cells
Glia in neuropathic disorders
RECENT PUBLICATIONS
Ye F, Chen Y, Hoang T, Montgomery RL, Zhao XH, Bu H, Hu T, Taketo MM, van Es JH, Clevers H, Hsieh J, Bassel-Duby R, Olson EN, Lu QR, "HDAC1 and HDAC2 Regulate Oligodendrocyte Differentiation By Disrupting β-Catenin-TCF Interaction" Nature Neuroscience, In press 2009
Wang, S., Dulin, J., Wu, H., Hurlock, E., Lee, S., Jansson, K., and Lu., Q. R., "An Oligodendrocyte-Specific Zinc Finger Transcription Regulator Cooperates With Olig2 To Promote Oligodendrocyte Differentiation" Development, 133(17):3389-98 2006
Yue, T., K. Xian, E. Hurlock, M. Xin, S. G. Kernie, L. F. Parada and Lu, Q. R., "A Critical Role for Dorsal Progenitors in Cortical Myelination" J. Neurosci., 26(4):1275-1280 January 2006
Cai J., Chen Y., Cai WH., Hurlock, EC., Wu H., Kernie, SG., Parada LF., Lu QR., "A Crucial Role For Olig2 In White Matter Astrocyte Development" Development, 134:1887-1899, 2007
Chen Y., Miles, DK., Hoang, T., Shi J., Hurlock E., Kernie KG., Lu QR., "The bHLH Transcription Factor Olig2 Is Critical For Reactive Astrocyte Proliferation After Cortical Injury" J. Neurosci., 28:10983-9 2008
SIGNIFICANT PUBLICATIONS
Ye F, Chen Y, Hoang T, Montgomery RL, Zhao XH, Bu H, Hu T, Taketo MM, van Es JH, Clevers H, Hsieh J, Bassel-Duby R, Olson EN, Lu QR, "HDAC1 and HDAC2 Regulate Oligodendrocyte Differentiation By Disrupting β-Catenin-TCF Interaction" Nature Neuroscience, In press, 2009
Lu QR, Cai L, Rowitch D, Cepko CL, Stiles CD., "Ectopic expression of Olig1 promotes oligodendrocyte formation and reduces neuronal survival in developing mouse cortex" Nat Neurosci., 109(1):75-86, 2001
Lu, Q.R., Yuk, D., Alberta, J.A., Zhu, Z., Pawlitzky, I., Chan, J., McMahon, A. P., Stiles, C. D. and Rowitch, D. H., "Sonic Hedgehog-Regulated Oligodendrocyte Lineage Genes Encoding bHLH Proteins in the Mammalian Central Nervous System." NEURON, 25:317-329, 2000
Lu, Q.R., Sun, T., Zhu, Z., Ma, N., Garcia, M., Stiles, C.D. and Rowitch, D., "Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection." Cell, 109:75-86, 2002
Lu, Q.R., Park, J., Noll, E, Chan, J.A., Alberta, J., Yuk, D., Alzamora, M.G., Louis, DN, Stiles, C.D, Rowitch, DH. and Black, PM., "Oligodendrocyte Lineage Genes (OLIG) as Molecular Markers for Human Glial Brain Tumors." Proc. Nat. Acad. Sci. USA, 98:10851-10856, 2001
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