Photo of Larry Sherman Ph.D

Larry Sherman Ph.D

    • Professor Oregon National Primate Research Center

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

  • "CD44 transmembrane receptor and hyaluronan regulate adult hippocampal neural stem cell quiescence and differentiation." Journal of Biological Chemistry In: , Vol. 292, No. 11, 17.03.2017, p. 4434-4445.
  • "Brg1 directly regulates Olig2 transcription and is required for oligodendrocyte progenitor cell specification." Developmental Biology In: , Vol. 413, No. 2, 15.05.2016, p. 173-187.
  • "Emerging roles of hyaluronic acid bioscaffolds in tissue engineering and regenerative medicine." International Journal of Biological Macromolecules In: , Vol. 86, 01.05.2016, p. 917-928.
  • "Immunopathology of Japanese macaque encephalomyelitis is similar to multiple sclerosis." Journal of Neuroimmunology In: , Vol. 291, 15.02.2016, p. 1-10.
  • "Neurofibromatosis as a gateway to better treatment for a variety of malignancies." Progress in Neurobiology  In: , 27.07.2015.
  • "Advances in Hyaluronan Biology : Signaling, Regulation, and Disease Mechanisms." International Journal of Cell Biology In: , Vol. 2015, 690572, 2015.
  • "Hyaluronan Synthesis, Catabolism, and Signaling in Neurodegenerative Diseases." International Journal of Cell Biology In: , Vol. 2015, 368584, 2015.
  • "Role of recurrent hypoxia-ischemia in preterm white matter injury severity." PLoS One In: , Vol. 9, No. 11, e112800, 12.11.2014.
  • "CD44 is required for spatial memory retention and sensorimotor functions." Behavioural Brain Research In: , Vol. 275, 16.09.2014, p. 146-149.
  • "CTF meeting 2012 : Translation of the basic understanding of the biology and genetics of NF1, NF2, and schwannomatosis toward the development of effective therapies." American Journal of Medical Genetics, Part A  In: , Vol. 164, No. 3, 03.2014, p. 563-578.
  • "Establishment and characterization of MRT cell lines from genetically engineered mouse models and the influence of genetic background on their development." International Journal of Cancer In: , Vol. 132, No. 12, 15.06.2013, p. 2767-2777.
  • "Hyaluronan oligosaccharides perturb lymphocyte slow rolling on brain vascular endothelial cells : Implications for inflammatory demyelinating disease." Matrix Biology In: , Vol. 32, No. 3-4, 24.04.2013, p. 160-168.
  • "Update from the 2011 International Schwannomatosis Workshop : From genetics to diagnostic criteria." American Journal of Medical Genetics, Part A  In: , Vol. 161, No. 3, 03.2013, p. 405-416.
  • "Paradoxical effects of apolipoprotein e on cognitive function and clinical progression in mice with experimental autoimmune encephalomyelitis." Pharmacology Biochemistry and Behavior  In: , Vol. 103, No. 4, 02.2013, p. 860-868.
  • "Digestion products of the PH20 hyaluronidase inhibit remyelination." Annals of Neurology In: , Vol. 73, No. 2, 02.2013, p. 266-280.
  • "Human neural stem cells induce functional myelination in mice with severe dysmyelination (Science Translational Medicine (2012) 4, (165er7))." Science Translational Medicine In: , Vol. 4, No. 165, 165er7, 19.12.2012.
  • "Conditional müller cell ablation causes independent neuronal and vascular pathologies in a novel transgenic model." Journal of Neuroscience In: , Vol. 32, No. 45, 07.11.2012, p. 15715-15727.
  • "Human neural stem cells induce functional myelination in mice with severe dysmyelination." Science Translational Medicine In: , Vol. 4, No. 155, 155ra136, 10.10.2012.
  • "Age-related changes in human and non-human primate white matter : From myelination disturbances to cognitive decline." Age In: , Vol. 34, No. 5, 10.2012, p. 1093-1110.
  • "Hyaluronan anchored to activated CD44 on central nervous system vascular endothelial cells promotes lymphocyte extravasation in experimental autoimmune encephalomyelitis." Journal of Biological Chemistry In: , Vol. 287, No. 40, 28.09.2012, p. 33237-33251.
  • "Astrocytes in aged nonhuman primate brain gray matter synthesize excess hyaluronan." Neurobiology of Aging In: , Vol. 33, No. 4, 04.2012.
  • "Arrested preoligodendrocyte maturation contributes to myelination failure in premature infants." Annals of Neurology In: , Vol. 71, No. 1, 01.2012, p. 93-109.
  • "Japanese macaque encephalomyelitis : A spontaneous multiple sclerosis-like disease in a nonhuman primate." Annals of Neurology In: , Vol. 70, No. 3, 09.2011, p. 362-373.
  • "White matter lesions defined by diffusion tensor imaging in older adults." Annals of Neurology In: , Vol. 70, No. 3, 09.2011, p. 465-476.
  • "Brain region-specific expression of Fxyd1, an Mecp2 target gene, is regulated by epigenetic mechanisms." Journal of Neuroscience Research In: , Vol. 89, No. 6, 06.2011, p. 840-851.
  • "Neural stem cell niches : Roles for the hyaluronan-based extracellular matrix." Frontiers in Bioscience - Scholar In: , Vol. 3 S, No. 3, 06.01.2011, p. 1165-1179.
  • "An organotypic slice culture model of chronic white matter injury with maturation arrest of oligodendrocyte progenitors." Molecular Neurodegeneration In: , Vol. 6, No. 1, 46, 2011.
  • "Treatment with selective estrogen receptor modulators regulates myelin specific T-cells and suppresses experimental autoimmune encephalomyelitis." GLIA In: , Vol. 57, No. 7, 2009, p. 777-790.
  • "Arrested oligodendrocyte lineage maturation in chronic perinatal white matter injury." Annals of Neurology In: , Vol. 63, No. 4, 04.2008, p. 520-530.
  • "A 'GAG' reflex prevents repair of the damaged CNS." Trends in Neurosciences In: , Vol. 31, No. 1, 01.2008, p. 44-52.

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