Professional Education

  • Doctor of Philosophy, S.U.N.Y. State University at Stony Brook (2012)
  • Bachelor of Science, San Francisco State University (2002)

Stanford Advisors


Journal Articles

  • beta 1 integrins are required for normal CNS myelination and promote AKT-dependent myelin outgrowth DEVELOPMENT Barros, C. S., Nguyen, T., Spencer, K. S., Nishiyama, A., Colognato, H., Mueller, U. 2009; 136 (16): 2717-2724


    Oligodendrocytes in the central nervous system (CNS) produce myelin sheaths that insulate axons to ensure fast propagation of action potentials. beta1 integrins regulate the myelination of peripheral nerves, but their function during the myelination of axonal tracts in the CNS is unclear. Here we show that genetically modified mice lacking beta1 integrins in the CNS present a deficit in myelination but no defects in the development of the oligodendroglial lineage. Instead, in vitro data show that beta1 integrins regulate the outgrowth of myelin sheaths. Oligodendrocytes derived from mutant mice are unable to efficiently extend myelin sheets and fail to activate AKT (also known as AKT1), a kinase that is crucial for axonal ensheathment. The inhibition of PTEN, a negative regulator of AKT, or the expression of a constitutively active form of AKT restores myelin outgrowth in cultured beta1-deficient oligodendrocytes. Our data suggest that beta1 integrins play an instructive role in CNS myelination by promoting myelin wrapping in a process that depends on AKT.

    View details for DOI 10.1242/dev.038679

    View details for Web of Science ID 000268312800005

    View details for PubMedID 19633169

  • Identification of dystroglycan as a second laminin receptor in oligodendrocytes, with a role in myelination DEVELOPMENT Colognato, H., Galvin, J., Wang, Z., Relucio, J., Nguyen, T., Harrison, D., Yurchenco, P. D., Ffrench-Constant, C. 2007; 134 (9): 1723-1736


    Developmental abnormalities of myelination are observed in the brains of laminin-deficient humans and mice. The mechanisms by which these defects occur remain unknown. It has been proposed that, given their central role in mediating extracellular matrix (ECM) interactions, integrin receptors are likely to be involved. However, it is a non-integrin ECM receptor, dystroglycan, that provides the key linkage between the dystrophin-glycoprotein complex (DGC) and laminin in skeletal muscle basal lamina, such that disruption of this bridge results in muscular dystrophy. In addition, the loss of dystroglycan from Schwann cells causes myelin instability and disorganization of the nodes of Ranvier. To date, it is unknown whether dystroglycan plays a role during central nervous system (CNS) myelination. Here, we report that the myelinating glia of the CNS, oligodendrocytes, express and use dystroglycan receptors to regulate myelin formation. In the absence of normal dystroglycan expression, primary oligodendrocytes showed substantial deficits in their ability to differentiate and to produce normal levels of myelin-specific proteins. After blocking the function of dystroglycan receptors, oligodendrocytes failed both to produce complex myelin membrane sheets and to initiate myelinating segments when co-cultured with dorsal root ganglion neurons. By contrast, enhanced oligodendrocyte survival in response to the ECM, in conjunction with growth factors, was dependent on interactions with beta-1 integrins and did not require dystroglycan. Together, these results indicate that laminins are likely to regulate CNS myelination by interacting with both integrin receptors and dystroglycan receptors, and that oligodendrocyte dystroglycan receptors may have a specific role in regulating terminal stages of myelination, such as myelin membrane production, growth, or stability.

    View details for DOI 10.1242/dev.02819

    View details for Web of Science ID 000245687300011

    View details for PubMedID 17395644

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