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Alexander Smith, PhD

Title(s)Assistant Researcher, Medicine
SchoolSchool of Medicine
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    I work on the mechanisms of fluid transport by astrocytes in the brain. Currently we are investigating how the spatial organization of water transporters in the astrocyte plasma membrane contributes to interstitial fluid homeostasis and to the brain response following amyloid deposition in Alzheimer's disease.

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    Visualizing the distribution of large molecule therapeutics in optic nerve
    NIH/NEI R21EY029881Jan 1, 2019 - Dec 31, 2020
    Role: Principal Investigator
    Role Description: The major goals of this project are to determine the extent to which CSF solutes can reach the optic nerve and retina, and to test the feasibility of delivering large molecule therapeutics to the optic nerve by intrathecal injection
    AQP4 mislocalization and glucose hypometabolism in Alzheimer's Disease
    BrightFocus Foundation A2018351SAug 1, 2018 - Aug 1, 2021
    Role: Principal Investigator
    Role Description: The major goal of this award is to test the novel hypothesis that AQP4 mislocalization is the cause of glucose hypometabolism in AD. Further studies will determine the mechanism of AQP4 mislocalization in a mouse model of AD, and investigate the utility of correcting the AQP4 mislocalization defect as a therapeutic approach for rescuing impaired glucose metabolism in AD.

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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    1. Smith AJ, Duan T, Verkman AS. Aquaporin-4 reduces neuropathology in a mouse model of Alzheimer's disease by remodeling peri-plaque astrocyte structure. Acta Neuropathol Commun. 2019 May 08; 7(1):74. PMID: 31068220.
      View in: PubMed
    2. Duan T, Smith AJ, Verkman AS. Complement-dependent bystander injury to neurons in AQP4-IgG seropositive neuromyelitis optica. J Neuroinflammation. 2018 Oct 22; 15(1):294. PMID: 30348195.
      View in: PubMed
    3. Verkman AS, Yao X, Smith AJ. The evolving mystery of why skeletal muscle is spared in seropositive neuromyelitis optica. J Cell Mol Med. 2018 Mar; 22(3):2039-2040. PMID: 29363875.
      View in: PubMed
    4. Smith AJ, Verkman AS. The "glymphatic" mechanism for solute clearance in Alzheimer's disease: game changer or unproven speculation? FASEB J. 2018 02; 32(2):543-551. PMID: 29101220.
      View in: PubMed
    5. Verkman AS, Smith AJ, Phuan PW, Tradtrantip L, Anderson MO. The aquaporin-4 water channel as a potential drug target in neurological disorders. Expert Opin Ther Targets. 2017 12; 21(12):1161-1170. PMID: 29072508.
      View in: PubMed
    6. Smith AJ, Yao X, Dix JA, Jin BJ, Verkman AS. Test of the 'glymphatic' hypothesis demonstrates diffusive and aquaporin-4-independent solute transport in rodent brain parenchyma. Elife. 2017 08 21; 6. PMID: 28826498.
      View in: PubMed
    7. Tradtrantip L, Yao X, Su T, Smith AJ, Verkman AS. Bystander mechanism for complement-initiated early oligodendrocyte injury in neuromyelitis optica. Acta Neuropathol. 2017 07; 134(1):35-44. PMID: 28567523.
      View in: PubMed
    8. Verkman AS, Tradtrantip L, Smith AJ, Yao X. Aquaporin Water Channels and Hydrocephalus. Pediatr Neurosurg. 2017; 52(6):409-416. PMID: 27978530.
      View in: PubMed
    9. Jin BJ, Smith AJ, Verkman AS. Spatial model of convective solute transport in brain extracellular space does not support a "glymphatic" mechanism. J Gen Physiol. 2016 12; 148(6):489-501. PMID: 27836940.
      View in: PubMed
    10. Smith AJ, Verkman AS. Superresolution Imaging of Aquaporin-4 Cluster Size in Antibody-Stained Paraffin Brain Sections. Biophys J. 2015 Dec 15; 109(12):2511-2522. PMID: 26682810.
      View in: PubMed
    11. Smith AJ, Jin BJ, Verkman AS. Muddying the water in brain edema? Trends Neurosci. 2015 Jun; 38(6):331-2. PMID: 25980601.
      View in: PubMed
    12. Yao X, Smith AJ, Jin BJ, Zador Z, Manley GT, Verkman AS. Aquaporin-4 regulates the velocity and frequency of cortical spreading depression in mice. Glia. 2015 Oct; 63(10):1860-9. PMID: 25944186.
      View in: PubMed
    13. Ratelade J, Smith AJ, Verkman AS. Human immunoglobulin G reduces the pathogenicity of aquaporin-4 autoantibodies in neuromyelitis optica. Exp Neurol. 2014 May; 255:145-53. PMID: 24636863.
      View in: PubMed
    14. Smith AJ, Jin BJ, Ratelade J, Verkman AS. Aggregation state determines the localization and function of M1- and M23-aquaporin-4 in astrocytes. J Cell Biol. 2014 Feb 17; 204(4):559-73. PMID: 24515349; PMCID: PMC3926963.
    15. Dason JS, Smith AJ, Marin L, Charlton MP. Cholesterol and F-actin are required for clustering of recycling synaptic vesicle proteins in the presynaptic plasma membrane. J Physiol. 2014 Feb 15; 592(4):621-33. PMID: 24297851.
      View in: PubMed
    16. Dason JS, Smith AJ, Marin L, Charlton MP. Vesicular sterols are essential for synaptic vesicle cycling. J Neurosci. 2010 Nov 24; 30(47):15856-65. PMID: 21106824.
      View in: PubMed
    17. Smith AJ, Sugita S, Charlton MP. Cholesterol-dependent kinase activity regulates transmitter release from cerebellar synapses. J Neurosci. 2010 Apr 28; 30(17):6116-21. PMID: 20427669.
      View in: PubMed
    18. Silverman-Gavrila LB, Smith AJ. Facilitating exchange: activity-dependent regulation of presynaptic Na+/Ca2+ exchange. J Physiol. 2008 Apr 15; 586(8):2039-40. PMID: 18308821.
      View in: PubMed
    19. Means S, Smith AJ, Shepherd J, Shadid J, Fowler J, Wojcikiewicz RJ, Mazel T, Smith GD, Wilson BS. Reaction diffusion modeling of calcium dynamics with realistic ER geometry. Biophys J. 2006 Jul 15; 91(2):537-57. PMID: 16617072.
      View in: PubMed
    20. Hernandez-Hansen V, Smith AJ, Surviladze Z, Chigaev A, Mazel T, Kalesnikoff J, Lowell CA, Krystal G, Sklar LA, Wilson BS, Oliver JM. Dysregulated FcepsilonRI signaling and altered Fyn and SHIP activities in Lyn-deficient mast cells. J Immunol. 2004 Jul 01; 173(1):100-12. PMID: 15210764.
      View in: PubMed
    21. Smith AJ, Pfeiffer JR, Zhang J, Martinez AM, Griffiths GM, Wilson BS. Microtubule-dependent transport of secretory vesicles in RBL-2H3 cells. Traffic. 2003 May; 4(5):302-12. PMID: 12713658.
      View in: PubMed
    22. Smith AJ, Surviladze Z, Gaudet EA, Backer JM, Mitchell CA, Wilson BS. p110beta and p110delta phosphatidylinositol 3-kinases up-regulate Fc(epsilon)RI-activated Ca2+ influx by enhancing inositol 1,4,5-trisphosphate production. J Biol Chem. 2001 May 18; 276(20):17213-20. PMID: 11279065.
      View in: PubMed
    23. Wilson BS, Pfeiffer JR, Smith AJ, Oliver JM, Oberdorf JA, Wojcikiewicz RJ. Calcium-dependent clustering of inositol 1,4,5-trisphosphate receptors. Mol Biol Cell. 1998 Jun; 9(6):1465-78. PMID: 9614187; PMCID: PMC25370.