How axon-Schwann cell interactions regulate the development and regeneration of peripheral nerve and the pathogenesis of peripheral neuropathy. My current projects relate to (1) the role of connexin32 in the pathogenesis of inherited demyelinating neuropathy, (2) how gap junctions between astrocytes and oligodendrocytes affect the structure/function of CNS myelin, (3) how the myelin sheath organizes the structure of the axon, and (4) the role of Schwann cells in axonal regeneration.
Light, confocal, and electron microscopy, immunocytochemistry, creating and analyzing transgenic mice, Northern and Western blotting, Schwann cell culture, transfecting cells.
My main interest is the pathogenesis of inherited demyelinating neuropathies, particularly the role of a gap junction protein, connexin32, in the myelin sheath. Mutations in the connexin32 gene cause one form of inherited demyelinating neuropathy in humans (and in mice), and my colleagues and I showed that the connexin32 is localized in myelin sheaths, that myelin sheaths have functional gap junctions, and that many connexin32 mutants have abnormal trafficking. We are actively studying how connexin32 mutants cause demyelinating in Schwann cells, and how some connexin32 mutants may affect the other connexins expressed by myelinating Schwann cells and oligodendrocytes.
Our second area of active investigation is the molecular organization of myelinated axons - the basis for saltatory conduction. We are investigating the role of two K+ channels in axonal conduction. In addition, we are examining how the axonal membrane is reorganized during demyelination and remyelination. These findings have important implications for restoring conduction in demyelinating diseases.
The diagnosis and management of peripheral neuropathies.
Clinical electrophysiology - EMG
Scherer, S.S. and K.A. Kleopa : X-linked Charcot-Marie-Tooth disease. Peripheral Neuropathy, 4th edition. P.J. Dyck and P.K. Thomas (eds.). Saunders, Philadelphia Page: 1791-1804, 2005.
Scherer, S.S. and E.J. Arroyo: Schwann cells. Encyclopedia of Life Sciences. Macmillan Reference Ltd., London, 2005.
Scherer, S.S. : Hereditary Neuropathies. Encyclopedic Reference of Pain. R.F. Schmidt and W.D. Willis, eds (eds.). Springer-Verlag, 2005 Notes: in press.
Devaux, J.J., and S.S. Scherer: Altered ion channels in an animal model of Charcot-Marie-Tooth disease type IA. J. Neurosci. 25: 1470-1480, 2005.
Scherer, S.S., Y.-T. Xu, A. Messing, K. Willecke, K.H. Fischbeck, and L.J. Bone Jeng : Transgenic expression of human Connexin32 in myelinating Schwann cells prevents demyelination in connexin32-null mice. J. Neurosci. 25: 1550-1559, 2005.
Liang, G.S. Lin, M. de Miguel, J.M. Gomez-Hernandez, J.D. Glass, S.S. Scherer, M. Mintz, L.C. Barrio, and K.H. Fischbeck : Severe neuropathy with leaky connexin32 hemichannels. Ann. Neurol. 57: 749-754, 2005.
Huang, Y., E.E. Sirkowski, J.T. Stickney, and S.S. Scherer : Prenylation-defective human connexin32 mutants are normally localized and function equivalently to wild type connexin32 in myelinating Schwann cells. J. Neurosci. 25: 7111-7120, 2005.
Occhi, S., D. Zambroni, U. Del Carro, S. Amadio, E.E. Sirkowsi, S.S. Scherer, K. Campbell, S.A. Moore, Z.-L. Chen, S. Strickland, A. Di Muzio, A. Uncini, L. Wrabetz, and M.-L. Feltri : Both laminin and Schwann cell dystroglycan are necessary for proper clustering of sodium channels at nodes of Ranvier. J. Neurosci. 21: 9418-9427, 2005.
Devaux, J., K.A. Kleopa, E.C. Cooper*, and S.S. Scherer* : KCNQ2 is a nodal K+ channel. J. Neurosci. 24: 1236-44, 2004 Notes: and Comment.
Kleopa, K.A., J.L. Orthmann, A. Enriquez, D.L. Paul, and S.S. Scherer : Unique distributions of the gap junction proteins connexin29, connexin32, and connexin47 in oligodendrocytes. Glia 2004 Notes: In press.
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Last updated: 09/12/2012
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