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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  • "Discovery of a CLN7 model of Batten disease in non-human primates." Neurobiology of Disease  In: , Vol. 119, 01.11.2018, p. 65-78.
  • "A TLR/AKT/FoxO3 immune tolerance-like pathway disrupts the repair capacity of oligodendrocyte progenitors." Journal of Clinical Investigation  In: , Vol. 128, No. 5, 01.05.2018, p. 2025-2041.
  • "Distinct roles for hyaluronan in neural stem cell niches and perineuronal nets." Matrix Biology  In: , 01.01.2018.
  • "Antenatal prevention of cerebral palsy and childhood disability : Is the impossible possible?" Journal of Physiology  In: , 01.01.2018.
  • "Comment on : PH20 is not expressed in murine CNS and oligodendrocyte precursor cells." Annals of Clinical and Translational Neurology  In: , Vol. 4, No. 8, 01.08.2017, p. 608-609.
  • "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.

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