Lu Lab

  • Lu Lab Research

    Understanding myelinating glial development, function and brain cancers

    Lu lab studies development of myelinating glial cells including oligodendrocytes and Schwann cells in the CNS and PNS, respectively, to elucidate the molecular basis underlying glial cell differentiation, function and brain tumor formation. We employ comprehensive molecular and cellular technology, bioinformatics, in combination with conditional gene targeting in mice to define the mechanisms of glial subtype development, myelination and cancers.

    We use transgenic animal models for in vivo mutagenesis and fate mapping to identify myelinating progenitor cells and define the myelination process during development and under pathological conditions. We have focused on discovering novel transcription factors that control oligodendrocyte differentiation and myelination. Most recently, we have explored epigenetic mechanisms including chromatin remodeling molecules and small non-coding RNAs (microRNAs) in the control of oligodendrocyte development and demyelinating diseases. Our long-term goal is to delineate the comprehensive molecular and genetic pathways for the formation and function of glial cell types and to use this information to develop effective therapies for inherited and acquired demyelinating diseases in humans and brain cancers.

    Currently, the Lu lab seeks to address following questions:

    • What are transcriptional and signaling networks that control myelination in CNS and PNS?
    • How do glial lineage-specific gene transcription program govern glial progenitor cell proliferation and differentiation?
    • What are the molecules and pathways that promote myelin repair?
    • What are molecular and cellular mechanisms controlling myelin homeostasis?
    • What are progenitor cell sources and mechanisms that control initiation of brain cancers?
  • Lab Publications

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    2014

    He, X., Zhang, L., Chen, Y., Remke, M., Shih, D., Lu, F., Wang, H., Deng, Y., Yu, Y., Xia, Y., Wu, X., Ramaswamy, V., Hu, T., Wang, F., Zhou, W., Burns, D. K., Kim, S. H., Kool, M., Pfister, S., Weinstein, L. S., Pomeroy, S., Gilbertson, R., Rubin, J. B., Hou, Y., Wechsler-Reya, R., Taylor, M.D., and Lu, Q. R. The G-protein Alpha Subunit Gsα Is A Tumor Suppressor In Sonic Hedgehog driven Medulloblastoma. Nature Medicine, doi:10.1038/nm.3666, Aug. 25, 2014.

    2013

    Hennen S*, Wang H*, Peters L, Merten N, Simon K, Spinrath A, Blättermann S, Akkari R, Schrage R, Schröder R, Schulz D, Vermeiren C, Zimmermann K, Kehraus S, Drewke C, Pfeifer A, König G, Mohr K, Gillard M, Müller C, Lu QR, Gomeza J, Kostenis E. Decoding signaling and function of the orphan G protein-coupled receptor Gpr17 with a small molecule agonist. Sci Signal. 2013 Oct 22;6(298):ra93. *Co-first authors.

    Limpert AS, Bai S, Narayan M, Wu J, Yoon SO, Carter BD*, Lu QR*. NF-kB forms a complex with the chromatin remodeler BRG1 to regulate Schwann cell differentiation. J Neurosci. 2013 Feb 6;33(6):2388-97. *Co-corresponding authors.

    Yu Y, Chen Y, Kim B, Wang H, Zhao C, He X, Liu L, Liu W, Wu, LM, Mao M, Chan JR, Wu J, Lu QR. Olig2 targets chromatin remodelers to enhancers to initiate oligodendrocyte differentiation. Cell. 2013 Jan 17;152(1-2): 248–261.

    2012

    Chong SY, Rosenberg SS, Fancy SP, Zhao C, Shen YA, Hahn AT, McGee AW, Xu X, Zheng B, Zhang LI, Rowitch DH, Franklin RJ, Lu QR*, Chan JR*. Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of oligodendrocyte myelination. Proc Natl Acad Sci U S A. 2012 Jan 24:109(4):1299-304. * Co-corresponding authors.

    Weng Q, Chen Y, Wang H, Xu X, Yang B, He Q, Shou W, Higashi Y, van den Berghe V, Seuntjens E, Kernie SG, Bukshpun P, Sherr EH, Huylebroeck D, Lu QR. Dual-mode modulation of Smad signaling by Smad-interacting protein Sip1 is required for myelination in the central nervous system. Neuron. 2012 Feb 23;73(4):713-28.

    Other Significant Publications

    Zhao XH, He X, Han X, Yu Y, Ye F, Chen Y, Hoang T, Xu X, Mi QS, Xin M, Wang F, Appel B, Lu QR. MicroRNA-Mediated Control of Oligodendrocyte Differentiation. Neuron. 2010 Mar 11; 65(5):612-26.

    Chen Y, Wu H, Wang S, Koito H, Li J, Ye F, Hoang J, Escobar SS, Arnett HA, Trapp BD, Karandikar NJ, Hsieh J, Lu QR. The oligodendrocyte-specific G-protein coupled receptor GPR17 is a cell-intrinsic timer of myelination. Nat Neurosci. 2009 Nov;12(11):1398-406.

    Ye F, Chen Y, Hoang T, Montgomery RL, Zhao XH, Bu H, Taketo MM, van Es JH, Clevers H, Hsieh J, Bassel-Duby R, Olson EN, Lu QR. Histone Deacetylases 1 and 2 Regulate Oligodendrocyte Differentiation By Disrupting beta-Catenin TCF Interaction. Nat Neurosci. 2009 Jul;12(7):829-38.

    Chen Y, Miles D, Hoang J, Shi J, Kernie SG, Lu QR. The bHLH Gene Olig2 Is Required for Reactive Astrocyte Proliferation After Cortical Injury. J Neurosci. 2008 Oct;28(44):1-5.