Photo of Larry Sherman, Ph.D

Larry Sherman Ph.D

    • Professor Oregon National Primate Research Center
    • Program in Molecular and Cellular Biosciences School of Medicine
    • Cell and Developmental Biology Graduate Program School of Medicine

The Sherman lab discovered that a high molecular weight form of HA accumulates in the nervous systems of humans and animals with a number of different neurodegenerative diseases and during the course of normative aging. HA can both control the proliferation of astrocytes, cells that respond to insults to the brain and spinal cord, and act to inhibit the maturation of oligodendrocyte progenitors, which are cells that form the myelin sheaths of central nervous system axons. This latter effect of HA appears to contribute to the failure of remyelination in diseases like multiple sclerosis and in the aging brain. Sherman's hypothesis is that by regulating how this HA accumulates in neurodegenerative conditions and diseases, it may be possible to promote remyelination and nervous system repair.

 

In addition, Sherman's group is studying how HA, CD44, and other molecules regulate the differentiation of neural stem cells - cells found both during embryonic development and in adults - that can give rise to all of the cell types in the brain and spinal cord. This research is focused on determining whether such cells can be stably expanded and differentiated into the damaged nervous system.

 

The group has also found that a chromatin remodeling factor, called Brahma-related gene-1 (Brg1), can regulate the expression of neuron and glial cell-type specific genes (including CD44), and that Brg1 may function through a mechanism that includes DNA methylation. These studies are revealing fundamental mechanisms that underlie normal brain development.

 

Brg1 is part of a larger complex of proteins, called SWI/SNF. Mutations in a gene that encodes another protein in the SWI/SNF complex, called SNF5, are linked to schwannomatosis, a disease characterized by multiple peripheral nerve sheath tumors and intractable pain. Thus, another area of interest in the Sherman lab is to understand how the loss of SWI/SNF activity and SNF5 in particular influences peripheral nerve tumorigenesis and pain.

 

The long-term aim of all of these studies is to develop experimental therapies for schwannomatosis, demyelinating diseases and related neurodegenerative conditions using both rodent and non-human primate models of these conditions.

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Publications

  • "Expression of multiple forms of bFGF in early avian embryos and their possible role in neural crest cell commitment" Annals of the New York Academy of Sciences  1991
  • "Brg1 is required for murine neural stem cell maintenance and gliogenesis" Developmental Biology January 15 2006
  • "A splice variant of CD44 expressed in the rat apical ectodermal ridge contributes to limb outgrowth" Annals of the New York Academy of Sciences  1996
  • "Mice with GFAP-targeted loss of neurofibromin demonstrate increased axonal MET expression with aging" GLIA May 2007
  • "Erbin regulates mitogen-activated protein (MAP) kinase activation and MAP kinase-dependent interactions between merlin and adherens junction protein complexes in Schwann cells" Journal of Biological Chemistry March 25 2005
  • "Multiple molecular weight forms of basic fibroblast growth factor are developmentally regulated in the rat central nervous system" Annals of the New York Academy of Sciences  1991
  • "CD44 overexpression by oligodendrocytes" GLIA September 2004
  • "Endometrial carcinoma cells are nonpermissive for CD44-erbB2 interactions" Applied Immunohistochemistry September 2002
  • "The BRG-1 Subunit of the SWI/SNF Complex Regulates CD44 Expression" Journal of Biological Chemistry March 23 2001
  • "Hyaluronan anchored to activated CD44 on central nervous system vascular endothelial cells promotes lymphocyte extravasation in experimental autoimmune encephalomyelitis" Journal of Biological Chemistry September 28 2012
  • "CD44 expression identifies astrocyte-restricted precursor cells" Developmental Biology December 1 2004
  • "Immunocytochemical assay for Ras activity" Methods in Enzymology  2001
  • "Role of recurrent hypoxia-ischemia in preterm white matter injury severity" PLoS One November 12 2014
  • "Arrested preoligodendrocyte maturation contributes to myelination failure in premature infants" Annals of Neurology January 2012
  • "Brain region-specific expression of Fxyd1, an Mecp2 target gene, is regulated by epigenetic mechanisms" Journal of Neuroscience Research June 2011
  • "SWI/SNF chromatin-remodeling factors induce changes in DNA methylation to promote transcriptional activation" Journal of Cancer Research May 1 2005
  • "Analysis of molecular functions of the tumor metastasis promoting surface molecule CD44v4-v7 using transgenic mice." Princess Takamatsu symposia  1994
  • "CD44 enhances neuregulin signaling by Schwann cells" Journal of Cell Biology September 4 2000
  • "Japanese macaque encephalomyelitis" Annals of Neurology September 2011
  • "Merlin" Trends in Cell Biology November 1 2001
  • "CD44-Independent Hepatocyte Growth Factor/c-Met Autocrine Loop Promotes Malignant Peripheral Nerve Sheath Tumor Cell Invasion In Vitro" GLIA February 2004
  • "Neural stem cell niches" Frontiers in Bioscience - Scholar January 6 2011
  • "How tumor cells make use of CD44" Cell Communication and Adhesion  1998
  • "Antisense Oligodeoxynucleotides Suppress Basic Fibroblast Growth Factor Expression in Glioma Cell Lines and Primary Cultures of Neural Crest Cells" Neuroprotocols February 1993
  • "CD44 associates with EGFR and erbB2 in metastasizing mammary carcinoma cells" Applied Immunohistochemistry  2002
  • "Human neural stem cells induce functional myelination in mice with severe dysmyelination" Science Translational Medicine October 10 2012
  • "White matter lesions defined by diffusion tensor imaging in older adults" Annals of Neurology September 2011
  • "Protein 4.1B expression is induced in mammary epithelial cells during pregnancy and regulates their proliferation" Oncogene September 29 2005
  • "Conditional müller cell ablation causes independent neuronal and vascular pathologies in a novel transgenic model" Journal of Neuroscience November 7 2012
  • "Overexpression of activated neu/erbB2 initiates immortalization and malignant transformation of immature Schwann cells in vitro" Oncogene November 18 1999

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