Alex Smith, PhD

Title(s)Assistant Professor, Ophthalmology
SchoolSchool of Medicine
Address10 Koret Way, #213
San Francisco CA 94117
ORCID ORCID Icon0000-0002-3034-9137 Additional info
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    Collapse Biography 
    Collapse Education and Training
    Cambridge University, Cambridge, UKBA06/1996Natural Sciences
    University of New Mexico, Albuquerque, NMPhD12/2004Cell Biology

    Collapse Overview 
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    Glial barriers form at the boundary of healthy nervous system tissue where they control exchange of substances with the surrounding fluids, form a protective barrier to seal off damaged areas and co-ordinate immune signalling with the periphery. By studying the molecular mechanisms that mediate glial barrier function we hope to improve understanding of their role in disease, optimize the delivery of therapeutics to the central nervous system and identify novel targets for therapeutic intervention.
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    Measuring fluid clearance pathways in retinal edema
    Retina Research Foundation Jan 1, 2023 - Dec 31, 2024
    Role: Principal Investigator
    Description: The goal of this project is to develop methods for measuring rates and pathways for clearance of extracellular solutes from the retina.
    Measuring impairment of extracellular solute transport in Alzheimer's disease
    NIH/NIA R21AG078873Aug 1, 2022 - Jul 31, 2024
    Role: Principal Investigator
    Description: The goal of this study is to use multiphoton photobleaching to determine how amyloid deposition alters local extracellular solute transport rates in the brain
    Imaging accumulation and clearance of CSF solutes in the retina
    Hellman Foundation Jul 1, 2022 - Jun 30, 2024
    Role: Principal Investigator
    Description: The goal of this study is to determine if CSF solutes can enter the retina during intracranial pressure elevation
    Visualizing the distribution of large molecule therapeutics in optic nerve
    NIH R21EY029881Jan 1, 2019 - Jun 30, 2021
    Role: Principal Investigator
    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
    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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    Collapse Publications
    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. to make corrections and additions.
    Newest   |   Oldest   |   Most Cited   |   Most Discussed   |   Timeline   |   Field Summary   |   Plain Text
    Altmetrics Details PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Large molecules from the cerebrospinal fluid enter the optic nerve but not the retina of mice. Fluids Barriers CNS. 2024 Jan 04; 21(1):1. Tong XJ, Akdemir G, Wadhwa M, Verkman AS, Smith AJ. PMID: 38178155; PMCID: PMC10768282.
      View in: PubMed   Mentions: 1     Fields:    Translation:HumansAnimals
    2. Application of fluorescent dextrans to the brain surface under constant pressure reveals AQP4-independent solute uptake. J Gen Physiol. 2021 08 02; 153(8). Smith AJ, Akdemir G, Wadhwa M, Song D, Verkman AS. PMID: 34128962; PMCID: PMC8210582.
      View in: PubMed   Mentions: 12     Fields:    Translation:AnimalsCells
    3. Ocular Surface Potential Difference Measured in Human Subjects to Study Ocular Surface Ion Transport. Transl Vis Sci Technol. 2020 10; 9(11):20. Pasricha ND, Smith AJ, Levin MH, Schallhorn JM, Verkman AS. PMID: 33117611; PMCID: PMC7571274.
      View in: PubMed   Mentions: 6     Fields:    Translation:Humans
    4. CrossTalk opposing view: Going against the flow: interstitial solute transport in brain is diffusive and aquaporin-4 independent. J Physiol. 2019 09; 597(17):4421-4424. Smith AJ, Verkman AS. PMID: 31389038; PMCID: PMC6717017.
      View in: PubMed   Mentions: 25     Fields:    Translation:AnimalsCells
    5. Complement-independent bystander injury in AQP4-IgG seropositive neuromyelitis optica produced by antibody-dependent cellular cytotoxicity. Acta Neuropathol Commun. 2019 07 11; 7(1):112. Duan T, Smith AJ, Verkman AS. PMID: 31296268; PMCID: PMC6621951.
      View in: PubMed   Mentions: 30     Fields:    Translation:HumansAnimalsCells
    6. Aquaporin-4 reduces neuropathology in a mouse model of Alzheimer's disease by remodeling peri-plaque astrocyte structure. Acta Neuropathol Commun. 2019 05 08; 7(1):74. Smith AJ, Duan T, Verkman AS. PMID: 31068220; PMCID: PMC6506955.
      View in: PubMed   Mentions: 39     Fields:    Translation:HumansAnimalsCells
    7. Complement-dependent bystander injury to neurons in AQP4-IgG seropositive neuromyelitis optica. J Neuroinflammation. 2018 Oct 22; 15(1):294. Duan T, Smith AJ, Verkman AS. PMID: 30348195; PMCID: PMC6198534.
      View in: PubMed   Mentions: 34     Fields:    Translation:AnimalsCells
    8. The evolving mystery of why skeletal muscle is spared in seropositive neuromyelitis optica. J Cell Mol Med. 2018 03; 22(3):2039-2040. Verkman AS, Yao X, Smith AJ. PMID: 29363875; PMCID: PMC5824395.
      View in: PubMed   Mentions: 1     Fields:    Translation:HumansCells
    9. The "glymphatic" mechanism for solute clearance in Alzheimer's disease: game changer or unproven speculation? FASEB J. 2018 02; 32(2):543-551. Smith AJ, Verkman AS. PMID: 29101220; PMCID: PMC5888402.
      View in: PubMed   Mentions: 76     Fields:    Translation:HumansAnimalsCells
    10. The aquaporin-4 water channel as a potential drug target in neurological disorders. Expert Opin Ther Targets. 2017 12; 21(12):1161-1170. Verkman AS, Smith AJ, Phuan PW, Tradtrantip L, Anderson MO. PMID: 29072508; PMCID: PMC6481624.
      View in: PubMed   Mentions: 78     Fields:    Translation:HumansAnimalsCells
    11. Test of the 'glymphatic' hypothesis demonstrates diffusive and aquaporin-4-independent solute transport in rodent brain parenchyma. Elife. 2017 08 21; 6. Smith AJ, Yao X, Dix JA, Jin BJ, Verkman AS. PMID: 28826498; PMCID: PMC5578736.
      View in: PubMed   Mentions: 179     Fields:    Translation:AnimalsCells
    12. Bystander mechanism for complement-initiated early oligodendrocyte injury in neuromyelitis optica. Acta Neuropathol. 2017 07; 134(1):35-44. Tradtrantip L, Yao X, Su T, Smith AJ, Verkman AS. PMID: 28567523; PMCID: PMC5600280.
      View in: PubMed   Mentions: 34     Fields:    Translation:AnimalsCells
    13. Aquaporin Water Channels and Hydrocephalus. Pediatr Neurosurg. 2017; 52(6):409-416. Verkman AS, Tradtrantip L, Smith AJ, Yao X. PMID: 27978530; PMCID: PMC5969073.
      View in: PubMed   Mentions: 16     Fields:    Translation:HumansAnimals
    14. 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. Jin BJ, Smith AJ, Verkman AS. PMID: 27836940; PMCID: PMC5129742.
      View in: PubMed   Mentions: 104     Fields:    Translation:Cells
    15. Superresolution Imaging of Aquaporin-4 Cluster Size in Antibody-Stained Paraffin Brain Sections. Biophys J. 2015 Dec 15; 109(12):2511-2522. Smith AJ, Verkman AS. PMID: 26682810; PMCID: PMC4699884.
      View in: PubMed   Mentions: 25     Fields:    Translation:HumansAnimalsCells
    16. Muddying the water in brain edema? Trends Neurosci. 2015 Jun; 38(6):331-2. Smith AJ, Jin BJ, Verkman AS. PMID: 25980601; PMCID: PMC4739497.
      View in: PubMed   Mentions: 26     Fields:    Translation:HumansAnimalsCells
    17. Aquaporin-4 regulates the velocity and frequency of cortical spreading depression in mice. Glia. 2015 Oct; 63(10):1860-9. Yao X, Smith AJ, Jin BJ, Zador Z, Manley GT, Verkman AS. PMID: 25944186; PMCID: PMC4743984.
      View in: PubMed   Mentions: 10     Fields:    Translation:AnimalsCells
    18. Human immunoglobulin G reduces the pathogenicity of aquaporin-4 autoantibodies in neuromyelitis optica. Exp Neurol. 2014 May; 255:145-53. Ratelade J, Smith AJ, Verkman AS. PMID: 24636863; PMCID: PMC4291172.
      View in: PubMed   Mentions: 15     Fields:    Translation:AnimalsCells
    19. 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. Smith AJ, Jin BJ, Ratelade J, Verkman AS. PMID: 24515349; PMCID: PMC3926963.
      View in: PubMed   Mentions: 68     Fields:    Translation:HumansAnimalsCells
    20. 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. Dason JS, Smith AJ, Marin L, Charlton MP. PMID: 24297851; PMCID: PMC3934705.
      View in: PubMed   Mentions: 21     Fields:    Translation:AnimalsCells
    21. Vesicular sterols are essential for synaptic vesicle cycling. J Neurosci. 2010 Nov 24; 30(47):15856-65. Dason JS, Smith AJ, Marin L, Charlton MP. PMID: 21106824; PMCID: PMC6633740.
      View in: PubMed   Mentions: 26     Fields:    Translation:AnimalsCells
    22. Cholesterol-dependent kinase activity regulates transmitter release from cerebellar synapses. J Neurosci. 2010 Apr 28; 30(17):6116-21. Smith AJ, Sugita S, Charlton MP. PMID: 20427669; PMCID: PMC6632591.
      View in: PubMed   Mentions: 23     Fields:    Translation:AnimalsCells
    23. Facilitating exchange: activity-dependent regulation of presynaptic Na+/Ca2+ exchange. J Physiol. 2008 Apr 15; 586(8):2039-40. Silverman-Gavrila LB, Smith AJ. PMID: 18308821; PMCID: PMC2465199.
      View in: PubMed   Mentions:    Fields:    Translation:AnimalsCells
    24. Reaction diffusion modeling of calcium dynamics with realistic ER geometry. Biophys J. 2006 Jul 15; 91(2):537-57. Means S, Smith AJ, Shepherd J, Shadid J, Fowler J, Wojcikiewicz RJ, Mazel T, Smith GD, Wilson BS. PMID: 16617072; PMCID: PMC1483115.
      View in: PubMed   Mentions: 47     Fields:    Translation:AnimalsCells
    25. Dysregulated FcepsilonRI signaling and altered Fyn and SHIP activities in Lyn-deficient mast cells. J Immunol. 2004 Jul 01; 173(1):100-12. Hernandez-Hansen V, Smith AJ, Surviladze Z, Chigaev A, Mazel T, Kalesnikoff J, Lowell CA, Krystal G, Sklar LA, Wilson BS, Oliver JM. PMID: 15210764.
      View in: PubMed   Mentions: 53     Fields:    Translation:AnimalsCells
    26. Microtubule-dependent transport of secretory vesicles in RBL-2H3 cells. Traffic. 2003 May; 4(5):302-12. Smith AJ, Pfeiffer JR, Zhang J, Martinez AM, Griffiths GM, Wilson BS. PMID: 12713658.
      View in: PubMed   Mentions: 36     Fields:    Translation:HumansAnimalsCells
    27. 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. Smith AJ, Surviladze Z, Gaudet EA, Backer JM, Mitchell CA, Wilson BS. PMID: 11279065.
      View in: PubMed   Mentions: 16     Fields:    Translation:AnimalsCells
    28. Calcium-dependent clustering of inositol 1,4,5-trisphosphate receptors. Mol Biol Cell. 1998 Jun; 9(6):1465-78. Wilson BS, Pfeiffer JR, Smith AJ, Oliver JM, Oberdorf JA, Wojcikiewicz RJ. PMID: 9614187; PMCID: PMC25370.
      View in: PubMed   Mentions: 38     Fields:    Translation:AnimalsCells
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