Alan S Verkman

Summary

Affiliation: University of California
Country: USA

Publications

  1. ncbi Role of aquaporin water channels in airway fluid transport, humidification, and surface liquid hydration
    Y Song
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA
    J Gen Physiol 117:573-82. 2001
  2. ncbi Role of aquaporin-4 in airspace-to-capillary water permeability in intact mouse lung measured by a novel gravimetric method
    Y Song
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 94143, USA
    J Gen Physiol 115:17-27. 2000
  3. ncbi Airway surface liquid osmolality measured using fluorophore-encapsulated liposomes
    S Jayaraman
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, 94143, USA
    J Gen Physiol 117:423-30. 2001
  4. ncbi Lessons on renal physiology from transgenic mice lacking aquaporin water channels
    A S Verkman
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco 94143 0521, USA
    J Am Soc Nephrol 10:1126-35. 1999
  5. ncbi Aquaporin water channels and endothelial cell function
    A S Verkman
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco 94143 0521, USA
    J Anat 200:617-27. 2002
  6. ncbi Structure and function of aquaporin water channels
    A S Verkman
    Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco 94143 0521, USA
    Am J Physiol Renal Physiol 278:F13-28. 2000
  7. ncbi Renal concentrating and diluting function in deficiency of specific aquaporin genes
    A S Verkman
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, 94143 0521, USA
    Exp Nephrol 10:235-40. 2002
  8. ncbi Aquaporin water channels and lung physiology
    A S Verkman
    Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143 0521, USA
    Am J Physiol Lung Cell Mol Physiol 278:L867-79. 2000
  9. ncbi Role of water channels in fluid transport studied by phenotype analysis of aquaporin knockout mice
    A S Verkman
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco 94143 0521, USA
    Exp Physiol 85:233S-241S. 2000
  10. ncbi Does aquaporin-1 pass gas? An opposing view
    A S Verkman
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco CA 94143 0521, USA
    J Physiol 542:31. 2002

Research Grants

  1. MECHANISMS OF WATER TRANSPORT IN RENAL EPITHELIA
    Alan Verkman; Fiscal Year: 2007
  2. Application of Novel Optial Methods to Cell Dynamics
    Alan Verkman; Fiscal Year: 2007

Collaborators

Detail Information

Publications101 found, 100 shown here

  1. ncbi Role of aquaporin water channels in airway fluid transport, humidification, and surface liquid hydration
    Y Song
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA
    J Gen Physiol 117:573-82. 2001
    ..These results establish the fluid transporting properties of mouse airways, and indicate that aquaporins play at most a minor role in airway humidification, ASL hydration, and isosmolar fluid absorption...
  2. ncbi Role of aquaporin-4 in airspace-to-capillary water permeability in intact mouse lung measured by a novel gravimetric method
    Y Song
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 94143, USA
    J Gen Physiol 115:17-27. 2000
    ..AQP1 null mice. These results establish a simple gravimetric method to quantify osmosis and filtration in intact mouse lung and provide direct evidence for a contribution of the distal airways to airspace-to-capillary water transport...
  3. ncbi Airway surface liquid osmolality measured using fluorophore-encapsulated liposomes
    S Jayaraman
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, 94143, USA
    J Gen Physiol 117:423-30. 2001
    ..ASL fluid is approximately isosmolar under normal physiological conditions, but can become hyperosmolar when exposed to dry air, which may induce cough and airway reactivity in some patients...
  4. ncbi Lessons on renal physiology from transgenic mice lacking aquaporin water channels
    A S Verkman
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco 94143 0521, USA
    J Am Soc Nephrol 10:1126-35. 1999
    ..This article describes new renal physiologic insights revealed by phenotype analysis of aquaporin-knockout mice and the prospects for further basic and clinical developments...
  5. ncbi Aquaporin water channels and endothelial cell function
    A S Verkman
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco 94143 0521, USA
    J Anat 200:617-27. 2002
    ..Improved understanding of aquaporin-endothelial biology may lead to novel therapies for human disease, such as pharmacological modulation of corneal fluid transport, renal fluid clearance and intestinal absorption...
  6. ncbi Structure and function of aquaporin water channels
    A S Verkman
    Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco 94143 0521, USA
    Am J Physiol Renal Physiol 278:F13-28. 2000
    ..Recent results from knockout mice implicating multiple physiological roles of aquaporins suggest that the aquaporins may be suitable targets for drug discovery by structure-based and/or high-throughput screening strategies...
  7. ncbi Renal concentrating and diluting function in deficiency of specific aquaporin genes
    A S Verkman
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, 94143 0521, USA
    Exp Nephrol 10:235-40. 2002
    ..The renal phenotype in aquaporin null mice suggests the utility of aquaporin blockers as novel aquaretic-diuretic agents...
  8. ncbi Aquaporin water channels and lung physiology
    A S Verkman
    Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143 0521, USA
    Am J Physiol Lung Cell Mol Physiol 278:L867-79. 2000
    ..However, there remain unresolved questions about possible non-water-transporting roles of AQPs and about the role of AQPs in airway physiology, pleural fluid dynamics, and edema after lung infection...
  9. ncbi Role of water channels in fluid transport studied by phenotype analysis of aquaporin knockout mice
    A S Verkman
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco 94143 0521, USA
    Exp Physiol 85:233S-241S. 2000
    ..The physiological data on aquaporin null mice suggest the utility of aquaporin blockers and aquaporin gene replacement in selected human diseases...
  10. ncbi Does aquaporin-1 pass gas? An opposing view
    A S Verkman
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco CA 94143 0521, USA
    J Physiol 542:31. 2002
  11. ncbi Role of airway surface liquid and submucosal glands in cystic fibrosis lung disease
    A S Verkman
    Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California San Francisco, 1246 Health Sciences East Tower, San Francisco, CA 94143 0521, USA
    Am J Physiol Cell Physiol 284:C2-15. 2003
    ..New model systems and measurement technologies are being developed to make progress in establishing lung disease mechanisms in CF, which should facilitate mechanism-based design of therapies for CF...
  12. ncbi Aquaporin gene delivery to kidney
    Alan S Verkman
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, CA 94143 0521, USA
    Kidney Int 61:S120-4. 2002
    ..We reasoned that these mice could serve as useful models for gene replacement because of their predictable and unambiguous phenotypes...
  13. ncbi Physiological importance of aquaporins: lessons from knockout mice
    A S Verkman
    Cardiovascular Research Institute, University of California, San Francisco 94143 0521, USA
    Curr Opin Nephrol Hypertens 9:517-22. 2000
    ..The phenotype data obtained from aquaporin knockout mice suggest the utility of aquaporin blockers as novel diuretic agents...
  14. ncbi Solute and macromolecule diffusion in cellular aqueous compartments
    Alan S Verkman
    1246 Health Sciences East Tower, Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94143 0521, USA
    Trends Biochem Sci 27:27-33. 2002
    ..Possible implications of regulated molecular diffusion as a rate-limiting step in cell metabolism, and with respect to the delivery of therapeutic agents, are discussed...
  15. ncbi Physiological importance of aquaporin water channels
    Alan S Verkman
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco 94143 0521, USA
    Ann Med 34:192-200. 2002
    ..The transgenic mouse studies suggest that aquaporin inhibitors may have clinical indications as diuretics and in the treatment of cerebral edema, elevated intraocular pressure, and other conditions of abnormal fluid homeostasis...
  16. ncbi Role of aquaporin water channels in kidney and lung
    A S Verkman
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco 94143 0521, USA
    Am J Med Sci 316:310-20. 1998
    ..The transgenic mouse and mammalian cell models are thus beginning to provide clues about the role of aquaporins in normal physiology and disease...
  17. ncbi CFTR chloride channel drug discovery--inhibitors as antidiarrheals and activators for therapy of cystic fibrosis
    A S Verkman
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143 0521, USA
    Curr Pharm Des 12:2235-47. 2006
    ..Small molecule modulators of CFTR function may be useful in the treatment of cystic fibrosis, secretory diarrhea and polycystic kidney disease...
  18. ncbi Roles of aquaporins in kidney revealed by transgenic mice
    A S Verkman
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143 0521, USA
    Semin Nephrol 26:200-8. 2006
    ..The mouse phenotype data suggest the renal AQPs as targets for the development of aquaretics and potentially for therapy of cystic renal disease and acute renal injury...
  19. ncbi Three distinct roles of aquaporin-4 in brain function revealed by knockout mice
    A S Verkman
    Departments of Medicine and Physiology, Cardiovascular Research Institute, 1246 Health Sciences East Tower, Box 0521, University of California, San Francisco, CA 94143 0521, USA
    Biochim Biophys Acta 1758:1085-93. 2006
    ..Based on these findings, we propose modulation of AQP4 expression or function as a novel therapeutic strategy for a variety of cerebral disorders including stroke, tumor, infection, hydrocephalus, epilepsy, and traumatic brain injury...
  20. ncbi Aquaporins in endothelia
    A S Verkman
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143 0521, USA
    Kidney Int 69:1120-3. 2006
    ..AQP1 facilitates endothelial cell migration by a mechanism that may involve facilitated water transport across cell protrusions (lamellipodia). AQP1 inhibitors may thus have aquaretic and antiangiogenic activity...
  21. ncbi Novel roles of aquaporins revealed by phenotype analysis of knockout mice
    A S Verkman
    University of California, Department of Medicine, Cardiovascular Research Institute, San Francisco, 94143 0521 CA, USA
    Rev Physiol Biochem Pharmacol 155:31-55. 2005
    ..The mouse phenotype data suggest that modulators of AQP expression/function may have such wide-ranging clinical applications as diuretics and in the treatment of brain swelling, glaucoma, epilepsy, obesity, and cancer...
  22. ncbi Water transport across mammalian cell membranes
    A S Verkman
    Department of Medicine, University of California, San Francisco 94143, USA
    Am J Physiol 270:C12-30. 1996
    ..Further work should be directed at elucidation of the role of water channels in normal physiology and disease, molecular analysis of regulatory mechanisms, and water channel structure determination at atomic resolution...
  23. ncbi More than just water channels: unexpected cellular roles of aquaporins
    A S Verkman
    Department of Medicine, Cardiovascular Research Institute, Room 1246, Box 0521 University of California San Francisco, San Francisco, CA 94143 0521, USA
    J Cell Sci 118:3225-32. 2005
    ..The many roles of AQPs could be exploited for clinical benefit; for example, treatments that modulate AQP expression/function could be used as diuretics, and in the treatment of brain swelling, glaucoma, epilepsy, obesity and cancer...
  24. ncbi Drug discovery and epithelial physiology
    Alan S Verkman
    Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, CA 94143 0521, USA
    Curr Opin Nephrol Hypertens 13:563-8. 2004
    ..The purpose of this review is to explain the small-molecule discovery process for investigators doing research in an academic setting, with emphasis on advances and directions in epithelial transport physiology...
  25. ncbi Drug discovery in academia
    A S Verkman
    Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143 0521, USA
    Am J Physiol Cell Physiol 286:C465-74. 2004
    ....
  26. ncbi Sodium and chloride concentrations, pH, and depth of airway surface liquid in distal airways
    Yuanlin Song
    1246 Health Sciences East Tower, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143 0521, USA
    J Gen Physiol 122:511-9. 2003
    ..These results establish a novel lung preparation and fluorescence approach to study distal airway physiology and provide the first data on the composition and depth of distal ASL...
  27. ncbi Role of aquaporin water channels in eye function
    A S Verkman
    Department of Medicine, Cardiovascular Research Institute, University of California, 1246 Health Sciences East Tower, San Francisco, CA 94143 0521, USA
    Exp Eye Res 76:137-43. 2003
    ..Pharmacological alteration of AQP function may provide a new approach for therapy of glaucoma, corneal edema, and other diseases of the eye associated with abnormalities in IOP or tissue hydration...
  28. ncbi Role of aquaporins in lung liquid physiology
    A S Verkman
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, CA 94143 0521, USA
    Respir Physiol Neurobiol 159:324-30. 2007
    ..Recent data outside of the lung implicating the involvement of AQPs in cell migration and proliferation suggests possible new roles for lung AQPs to be explored...
  29. ncbi Evidence against aquaporin-1-dependent CO2 permeability in lung and kidney
    Xiaohui Fang
    Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, CA 94143 0521, USA
    J Physiol 542:63-9. 2002
    ..The results provide direct evidence against physiologically significant transport of CO2 by AQP1 in mammalian lung and kidney...
  30. ncbi Erythrocyte water permeability and renal function in double knockout mice lacking aquaporin-1 and aquaporin-3
    B Yang
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California, 94143 0521, USA
    J Biol Chem 276:624-8. 2001
    ..The renal function studies indicate independent roles of AQP1 and AQP3 in countercurrent exchange and collecting duct osmotic equilibration, respectively...
  31. ncbi Diffusional mobility of the cystic fibrosis transmembrane conductance regulator mutant, delta F508-CFTR, in the endoplasmic reticulum measured by photobleaching of GFP-CFTR chimeras
    Peter M Haggie
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521, USA
    J Biol Chem 277:16419-25. 2002
    ....
  32. ncbi Pleural surface fluorescence measurement of Na+ and Cl- transport across the air space-capillary barrier
    Jinjun Jiang
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, 94143 - 0521, USA
    J Appl Physiol 94:343-52. 2003
    ..Our results establish a pleural surface fluorescence method to measure unidirectional Cl(-) and Na(+) flux in intact lung and provide evidence for cAMP-stimulated transcellular Cl(-) and Na(+) transport...
  33. ncbi Evidence against a role of mouse, rat, and two cloned human t1alpha isoforms as a water channel or a regulator of aquaporin-type water channels
    T Ma
    Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California, USA
    Am J Respir Cell Mol Biol 19:143-9. 1998
    ..The cloning of hT1alpha isoforms may permit the development of an assay of type I cell antigen in airspace fluid as a marker of human lung injury...
  34. ncbi A small molecule CFTR inhibitor produces cystic fibrosis-like submucosal gland fluid secretions in normal airways
    Jay R Thiagarajah
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California, USA
    FASEB J 18:875-7. 2004
    ....
  35. ncbi Nanomolar affinity small molecule correctors of defective Delta F508-CFTR chloride channel gating
    Hong Yang
    Department of Medicine, University of California, San Francisco, California 94143, USA
    J Biol Chem 278:35079-85. 2003
    ..In conjunction with correctors of defective Delta F508-CFTR processing, small molecule potentiators of defective Delta F508-CFTR gating may be useful for therapy of cystic fibrosis caused by the Delta F508 mutation...
  36. ncbi cDNA and genomic cloning of mouse aquaporin-2: functional analysis of an orthologous mutant causing nephrogenic diabetes insipidus
    B Yang
    Department of Physiology, Cardiovascular Research Institute, San Francisco, California, 94143 0521, USA
    Genomics 57:79-83. 1999
    ..The chemical chaperone glycerol produced a redistribution of Aqp2-T126M from ER to plasma membrane/endosomes. These results establish a basis for an Aqp2-T126M transgenic knock-in model of NDI...
  37. ncbi Thiophenecarboxylate suppressor of cyclic nucleotides discovered in a small-molecule screen blocks toxin-induced intestinal fluid secretion
    Lukmanee Tradtrantip
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, CA 94143 0521, USA
    Mol Pharmacol 75:134-42. 2009
    ....
  38. ncbi Increased diffusional mobility of CFTR at the plasma membrane after deletion of its C-terminal PDZ binding motif
    Peter M Haggie
    Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143 0521, USA
    J Biol Chem 279:5494-500. 2004
    ..PDZ-domain interactions of CFTR are thus dynamic and occur on a time scale of seconds or faster...
  39. ncbi The mercurial insensitive water channel (AQP-4) forms orthogonal arrays in stably transfected Chinese hamster ovary cells
    B Yang
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143 0521, USA
    J Biol Chem 271:4577-80. 1996
    ..These results provide direct evidence that a molecular water channel can spontaneously assemble in regular arrays...
  40. ncbi Increased seizure duration and slowed potassium kinetics in mice lacking aquaporin-4 water channels
    Devin K Binder
    Department of Neurological Surgery, University of California, San Francisco, 94110, USA
    Glia 53:631-6. 2006
    ..5 +/- 0.1 and 6.6 +/- 0.7 s, respectively). These results implicate AQP4 in the expression and termination of seizure activity and support the hypothesis that AQP4 is coupled to potassium homeostasis in vivo...
  41. ncbi Evidence against functionally significant aquaporin expression in mitochondria
    Baoxue Yang
    Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94143 0521, USA
    J Biol Chem 281:16202-6. 2006
    ....
  42. ncbi Role of aquaporins in alveolar fluid clearance in neonatal and adult lung, and in oedema formation following acute lung injury: studies in transgenic aquaporin null mice
    Y Song
    Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA
    J Physiol 525:771-9. 2000
    ....
  43. ncbi ClC-3 chloride channels facilitate endosomal acidification and chloride accumulation
    Mariko Hara-Chikuma
    Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143 0521, USA
    J Biol Chem 280:1241-7. 2005
    ..3 versus 5.9. Our results provide direct evidence for involvement of ClC-3 in endosomal acidification by Cl- shunting of the interior-positive membrane potential created by the vacuolar H+ pump...
  44. ncbi Aquaporin-dependent water permeation at the mouse ocular surface: in vivo microfluorimetric measurements in cornea and conjunctiva
    Marc H Levin
    Department of Medicine and Physiology, Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94143 0521, USA
    Invest Ophthalmol Vis Sci 45:4423-32. 2004
    ....
  45. ncbi High-affinity activators of cystic fibrosis transmembrane conductance regulator (CFTR) chloride conductance identified by high-throughput screening
    Tonghui Ma
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521, USA
    J Biol Chem 277:37235-41. 2002
    ..The new activators identified here may be useful in defining molecular mechanisms of CFTR activation and as lead compounds in CF drug development...
  46. ncbi Role of aquaporin water channels in pleural fluid dynamics
    Y Song
    Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143 0521, USA
    Am J Physiol Cell Physiol 279:C1744-50. 2000
    ..However, AQP1 does not appear to play a role in clinically relevant mechanisms of pleural fluid accumulation or clearance...
  47. ncbi Tear secretion by lacrimal glands in transgenic mice lacking water channels AQP1, AQP3, AQP4 and AQP5
    M Moore
    Department of Medicine, University of California, San Francisco 94143 0521, USA
    Exp Eye Res 70:557-62. 2000
    ..The requirement for aquaporins in salivary but not lacrimal gland secretion, may involve the substantially slower fluid secretion rate across lacrimal gland acinar cells...
  48. ncbi Phenotype analysis of aquaporin-8 null mice
    Baoxue Yang
    Cardiovascular Research Institute, Univ of California, San Francisco, CA 94143 0521, USA
    Am J Physiol Cell Physiol 288:C1161-70. 2005
    ..The mild phenotype of AQP8-null mice was surprising in view of the multiple phenotype abnormalities found in mouse models of AQP1-5 deficiency...
  49. ncbi In situ fluorescence measurement of tear film [Na+], [K+], [Cl-], and pH in mice shows marked hypertonicity in aquaporin-5 deficiency
    Javier Ruiz-Ederra
    Department of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143 0521, USA
    Invest Ophthalmol Vis Sci 50:2132-8. 2009
    ....
  50. ncbi Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption
    Samira Saadoun
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 94143, USA
    Nature 434:786-92. 2005
    ..Our findings support a fundamental role of water channels in cell migration, which is central to diverse biological phenomena including angiogenesis, wound healing, tumour spread and organ regeneration...
  51. ncbi cDNA cloning and gene structure of a novel water channel expressed exclusively in human kidney: evidence for a gene cluster of aquaporins at chromosome locus 12q13
    T Ma
    Department of Medicine, University of California, San Francisco 94143 0521, USA
    Genomics 35:543-50. 1996
    ..Further work is needed to establish the physiological significance of hKID...
  52. ncbi In vivo measurement of brain extracellular space diffusion by cortical surface photobleaching
    Devin K Binder
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 94143 0521, USA
    J Neurosci 24:8049-56. 2004
    ....
  53. ncbi Colon water transport in transgenic mice lacking aquaporin-4 water channels
    K S Wang
    Department of Surgery, Stanford University School of Medicine, CA 94143 0521, USA
    Am J Physiol Gastrointest Liver Physiol 279:G463-70. 2000
    ....
  54. ncbi Airway surface liquid pH in well-differentiated airway epithelial cell cultures and mouse trachea
    S Jayaraman
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521, USA
    Am J Physiol Cell Physiol 281:C1504-11. 2001
    ..The rapid response of ASL pH to changes in systemic acid-base status may contribute to airway hypersensitivity in asthma and other airway diseases...
  55. ncbi Optical measurement of swelling and water transport in spinal cord slices from aquaporin null mice
    E I Solenov
    Departments of Medicine and Physiology, 1246 Health Sciences East Tower, Cardiovascular Research Institute, University of California, San Francisco, CA 94143 0521, USA
    J Neurosci Methods 113:85-90. 2002
    ..These results establish a simple imaging method to map changes in water content of spinal cord slices, and provide evidence that aquaporins facilitate osmotic water transport in functionally relevant areas of the spinal cord...
  56. ncbi Severely impaired urinary concentrating ability in transgenic mice lacking aquaporin-1 water channels
    T Ma
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143 0521, USA
    J Biol Chem 273:4296-9. 1998
    ..The results suggest that AQP1 knockout mice are unable to create a hypertonic medullary interstitium by countercurrent multiplication. AQP1 is thus required for the formation of a concentrated urine by the kidney...
  57. ncbi Cloning of a novel rat kidney cDNA homologous to CHIP28 and WCH-CD water channels
    T Ma
    Department of Medicine, University of California, San Francisco 94143 0532
    Biochem Biophys Res Commun 197:654-9. 1993
    ..WCH3 is a new member of the MIP26 family of channel-forming proteins in mammalian kidney...
  58. ncbi Glial cell aquaporin-4 overexpression in transgenic mice accelerates cytotoxic brain swelling
    Baoxue Yang
    Departments of Medicine and Physiology, University of California San Francisco, 1246 Health Sciences East Tower, San Francisco, CA 94143 0521, USA
    J Biol Chem 283:15280-6. 2008
    ..We conclude that AQP4 expression is rate-limiting for brain water accumulation, and thus, that altered AQP4 expression can be functionally significant...
  59. ncbi Cloning, functional analysis and cell localization of a kidney proximal tubule water transporter homologous to CHIP28
    R Zhang
    Department of Medicine, University of California, San Francisco 94143 0532
    J Cell Biol 120:359-69. 1993
    ..These results indicate that CHIP28k is a major and highly selective water transporting protein in the kidney proximal tubule and thin descending limb of Henle, but not collecting duct...
  60. ncbi Small-molecule correctors of defective DeltaF508-CFTR cellular processing identified by high-throughput screening
    Nicoletta Pedemonte
    Department of Medicine, UCSF, San Francisco, California 94143 0521, USA
    J Clin Invest 115:2564-71. 2005
    ..Small-molecule correctors may be useful in the treatment of CF caused by the DeltaF508 mutation...
  61. ncbi Aquaporins and CFTR in ocular epithelial fluid transport
    M H Levin
    Department of Medicine, Cardiovascular Research Institute, Graduate Group in Biophysics, University of California, San Francisco, CA 94143-0521, USA
    J Membr Biol 210:105-15. 2006
    ..Recent data suggest AQPs and CFTR as attractive targets for drug development for therapy of keratoconjunctivitis sicca, recurrent corneal erosions, corneal edema, glaucoma, retinal detachment, and retinal ischemia...
  62. ncbi Expression, functional analysis, and in situ hybridization of a cloned rat kidney collecting duct water channel
    T Ma
    Department of Medicine, University of California, San Francisco 94143
    Am J Physiol 266:C189-97. 1994
    ..abstract truncated at 250 words)..
  63. ncbi Gene structure, cDNA cloning, and expression of a mouse mercurial-insensitive water channel
    T Ma
    Department of Medicine, University of California, San Francisco, California, 94143 0521, USA
    Genomics 33:382-8. 1996
    ..The genomic cloning of mMIWC represents the first step in the construction of a targeting vector for mMIWC gene knockout...
  64. ncbi Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema
    Marios C Papadopoulos
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, CA, 94143 0521, USA
    FASEB J 18:1291-3. 2004
    ..Thus, AQP4-mediated transcellular water movement is crucial for fluid clearance in vasogenic brain edema, suggesting AQP4 activation and/or up-regulation as a novel therapeutic option in vasogenic brain edema...
  65. ncbi Aquaporin-3-dependent cell migration and proliferation during corneal re-epithelialization
    Marc H Levin
    Department of Medicine and Physiology, Cardiovascular Research Institute, Graduate Group in Biophysics, University of California, San Francisco, California 94143 0521, USA
    Invest Ophthalmol Vis Sci 47:4365-72. 2006
    ..To determine a role for the water- and glycerol-transporting protein aquaporin-3 (AQP3) in mammalian corneal epithelium, where it is expressed but has no known function...
  66. ncbi Reduced osmotic water permeability of the peritoneal barrier in aquaporin-1 knockout mice
    B Yang
    Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143 0521, USA
    Am J Physiol 276:C76-81. 1999
    ..05 and 0.46 +/- 0.04 ml/h in (+/+) and (-/-) mice, respectively] were not affected by AQP1 deletion. Therefore, AQP1 provides a major route for osmotically driven water transport across the peritoneal barrier in peritoneal dialysis...
  67. ncbi Aquaporin deletion in mice reduces corneal water permeability and delays restoration of transparency after swelling
    Jay R Thiagarajah
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143 0521, USA
    J Biol Chem 277:19139-44. 2002
    ..The up-regulation of AQP1 expression and/or function in corneal endothelium may reduce corneal swelling and opacification following injury...
  68. ncbi In situ measurement of airway surface liquid [K+] using a ratioable K+-sensitive fluorescent dye
    Wan Namkung
    Departments of Medicine and Physiology, University of California, San Francisco, California 94143, USA
    J Biol Chem 284:15916-26. 2009
    ..Our results provide the first noninvasive measurements of [K(+)] in the ASL and indicate the involvement of apical and basolateral membrane ion transporters in maintaining a high ASL [K(+)]...
  69. ncbi Sevenfold-reduced osmotic water permeability in primary astrocyte cultures from AQP-4-deficient mice, measured by a fluorescence quenching method
    Eugen Solenov
    Department of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143 0521, USA
    Am J Physiol Cell Physiol 286:C426-32. 2004
    ..3 +/- 0.5 vs. 5.5 +/- 0.4 kcal/mol). Our studies establish a calcein quenching method for measurement of cell membrane water permeability and indicate that AQP-4 provides the principal route for water transport in astrocytes...
  70. ncbi Diffusion in the endoplasmic reticulum of an aquaporin-2 mutant causing human nephrogenic diabetes insipidus
    M H Levin
    Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143 0521
    J Biol Chem 276:21331-6. 2001
    ..These results indicate that the ER retention of AQP2-T126M does not result from restricted or slowed mobility and suggest that the majority of AQP2-T126M is not aggregated or bound to slowly moving membrane proteins...
  71. ncbi Chloride accumulation and swelling in endosomes enhances DNA transfer by polyamine-DNA polyplexes
    N D Sonawane
    Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA
    J Biol Chem 278:44826-31. 2003
    ..Our results provide direct support for the proton sponge hypothesis and thus a rational basis for the design of improved non-viral vectors for gene delivery...
  72. ncbi Lung fluid transport in aquaporin-5 knockout mice
    T Ma
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA
    J Clin Invest 105:93-100. 2000
    ..The unimpaired alveolar fluid clearance in AQP5-null mice indicates that high alveolar water permeability is not required for active, near-isosmolar fluid transport...
  73. ncbi Aquaporin-4 and brain edema
    Marios C Papadopoulos
    Department of Medicine, University of California, San Francisco, CA 94143 0521, USA
    Pediatr Nephrol 22:778-84. 2007
    ..These findings suggest that modulation of AQP4 expression or function may be beneficial in several cerebral disorders, including hyponatremic brain edema, hydrocephalus, stroke, tumor, infection, epilepsy, and traumatic brain injury...
  74. ncbi Small-molecule screen identifies inhibitors of a human intestinal calcium-activated chloride channel
    Ricardo de la Fuente
    1246 Health Sciences East Tower, Box 0521, University of California, San Francisco CA 94143 0521, USA
    Mol Pharmacol 73:758-68. 2008
    ..Small-molecule CaCC inhibitors may be useful in pharmacological dissection of CaCC functions and in reducing intestinal fluid losses in CaCC-mediated secretory diarrheas...
  75. ncbi cDNA cloning, gene organization, and chromosomal localization of a human mercurial insensitive water channel. Evidence for distinct transcriptional units
    B Yang
    Department of Medicine, University of California, San Francisco 94143 0521, USA
    J Biol Chem 270:22907-13. 1995
    ..The structural organization of the hMIWC gene represents a first step in definition of hMIWC differential expression, regulation, and possible role in human disease...
  76. ncbi Hypertonic saline therapy in cystic fibrosis: Evidence against the proposed mechanism involving aquaporins
    Marc H Levin
    Department of Medicine, University of California, San Francisco, California 94143-0521, USA
    J Biol Chem 281:25803-12. 2006
    ..Our data provide evidence against the mechanism proposed by Donaldson et al. to account for the effects of amiloride and hypertonic saline in CF lung disease, indicating the need to identify alternate mechanisms...
  77. ncbi Aquaporin water channels in transepithelial fluid transport
    Lukmanee Tradtrantip
    Department of Medicine, University of California, San Francisco, CA 94143 0521, USA
    J Med Invest 56:179-84. 2009
    ....
  78. ncbi Urearetics: a small molecule screen yields nanomolar potency inhibitors of urea transporter UT-B
    Marc H Levin
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143 0521, USA
    FASEB J 21:551-63. 2007
    ..UT-B inhibitors represent a new class of diuretics, "urearetics," which are predicted to increase renal water and solute clearance in water-retaining states...
  79. ncbi CFTR-adenylyl cyclase I association responsible for UTP activation of CFTR in well-differentiated primary human bronchial cell cultures
    Wan Namkung
    Department of Medicine and Physiology, University of California, San Francisco, CA 94143, USA
    Mol Biol Cell 21:2639-48. 2010
    ..We further conclude that CFTR is the principal chloride secretory pathway in non-CF airways for both cAMP and Ca(2+) agonists, providing a novel mechanism to link CFTR dysfunction to CF lung disease...
  80. ncbi Extracellular space diffusion in central nervous system: anisotropic diffusion measured by elliptical surface photobleaching
    Marios C Papadopoulos
    Departments of Medicine and Physiology, Cardiovascular Research Institute, 1246 Health Sciences East Tower, University of California-San Francisco, San Francisco, CA 94143, USA
    Biophys J 89:3660-8. 2005
    ..We suggest that the extracellular matrix might have evolved to facilitate rather than hinder diffusion even for large molecules...
  81. ncbi Carbon dioxide permeability of aquaporin-1 measured in erythrocytes and lung of aquaporin-1 null mice and in reconstituted proteoliposomes
    B Yang
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143 0521, USA
    J Biol Chem 275:2686-92. 2000
    ..These results provide direct evidence against physiologically significant AQP1-mediated CO(2) transport and establish an upper limit to the CO(2) permeability through single AQP1 water channels...
  82. ncbi Accelerated cataract formation and reduced lens epithelial water permeability in aquaporin-1-deficient mice
    Javier Ruiz-Ederra
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143 0521, USA
    Invest Ophthalmol Vis Sci 47:3960-7. 2006
    ..To investigate the involvement of aquaporin (AQP)-1 in lens epithelial cell water permeability and maintenance of lens transparency in experimental models of cataract formation...
  83. ncbi Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice
    C Bai
    Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143 0521, USA
    J Clin Invest 103:555-61. 1999
    ..AQP1 facilitates hydrostatically driven lung edema but is not required for active near-isosmolar absorption of alveolar fluid...
  84. ncbi Nephrogenic diabetes insipidus in mice lacking aquaporin-3 water channels
    T Ma
    Departments of Medicine, Physiology, and Pediatrics, Cardiovascular Research Institute, University of California, San Francisco, CA 94143 0521, USA
    Proc Natl Acad Sci U S A 97:4386-91. 2000
    ..Basolateral membrane aquaporins may thus provide blood-accessible targets for drug discovery of aquaretic inhibitors...
  85. ncbi Increased seizure threshold in mice lacking aquaporin-4 water channels
    Devin K Binder
    Department of Neurological Surgery, University of California, 505 Parnassus Ave, Box 0112, San Francisco, CA 94143, USA
    Neuroreport 15:259-62. 2004
    ..These results suggest that glial water channels may modulate brain excitability and the initiation and generalization of seizure activity...
  86. ncbi Generation and phenotype of a transgenic knockout mouse lacking the mercurial-insensitive water channel aquaporin-4
    T Ma
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143 0521, USA
    J Clin Invest 100:957-62. 1997
    ....
  87. ncbi Cell-based assay for high-throughput quantitative screening of CFTR chloride transport agonists
    L V Galietta
    Department of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521, USA
    Am J Physiol Cell Physiol 281:C1734-42. 2001
    ..The fluorescence assay and cell lines should facilitate the screening of novel CFTR activators and the characterization of alternative Cl(-) channels and transporters...
  88. ncbi Cloning of a novel water and urea-permeable aquaporin from mouse expressed strongly in colon, placenta, liver, and heart
    T Ma
    Department of Medicine, University of California, San Francisco 94143 0521, USA
    Biochem Biophys Res Commun 240:324-8. 1997
    ..2 x 10(-14) cm3/s. AQP8 is unique among the water channels in terms of its urea permeability and its strong expression in gastrointestinal organs, placenta and heart...
  89. ncbi Submucosal gland dysfunction as a primary defect in cystic fibrosis
    Danieli Salinas
    Department of Medicine, University of California, San Francisco, California 94143-0521, USA
    FASEB J 19:431-3. 2005
    ..Our results suggest that defective airway submucosal gland function is an early, primary defect in CF. Therapies directed at normalizing gland fluid secretion early in CF may thus reduce lung disease...
  90. ncbi Prevention of toxin-induced intestinal ion and fluid secretion by a small-molecule CFTR inhibitor
    Jay R Thiagarajah
    Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, 94143, USA
    Gastroenterology 126:511-9. 2004
    ..CONCLUSIONS: A small molecule CFTR blocker markedly reduced intestinal ion and fluid secretion caused by cAMP/cGMP-dependent bacterial enterotoxins. CFTR inhibition may thus reduce fluid secretion in infectious secretory diarrheas...
  91. ncbi Protective role of aquaporin-4 water channels after contusion spinal cord injury
    Atsushi Kimura
    Department of Neurological Surgery, University of California, Irvine, CA, USA
    Ann Neurol 67:794-801. 2010
    ..However, the mechanisms that control edema and the extent to which edema impacts outcome after SCI are not well elucidated...
  92. ncbi Chloride channels as drug targets
    Alan S Verkman
    Departments of Medicine and Physiology, University of California, San Francisco, California 94143 0521, USA
    Nat Rev Drug Discov 8:153-71. 2009
    ..Here, we discuss the broad opportunities that remain in chloride-channel-based drug discovery...
  93. ncbi Aquaporin-4: orthogonal array assembly, CNS functions, and role in neuromyelitis optica
    Alan S Verkman
    Department of Medicine, University of California, San Francisco, CA 94143 0521, USA
    Acta Pharmacol Sin 32:702-10. 2011
    ....
  94. ncbi Determinants of aquaporin-4 assembly in orthogonal arrays revealed by live-cell single-molecule fluorescence imaging
    Jonathan M Crane
    Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, CA 94143, USA
    J Cell Sci 122:813-21. 2009
    ....
  95. ncbi Diffusion in cells measured by fluorescence recovery after photobleaching
    Alan S Verkman
    University of California, San Francisco 94143, USA
    Methods Enzymol 360:635-48. 2003
  96. ncbi Expression and localization of aquaporin 1 and 3 in human fetal membranes
    Stephanie E Mann
    Department of Obstetrics, School of Medicine, University of California-San Francisco, 1001 Potrero Avenue 6D13, San Francisco, CA 94110, USA
    Am J Obstet Gynecol 187:902-7. 2002
    ..Further studies are needed to clarify our understanding of the role of fetal membrane aquaporins in amniotic fluid homeostasis...
  97. ncbi Reduced PDZ Interactions of Rescued ΔF508CFTR Increases Its Cell Surface Mobility
    Cathleen D Valentine
    From the Department of Medicine, University of California, San Francisco, California 94143 0521 and
    J Biol Chem 287:43630-8. 2012
    ..Our surface diffusion measurements in live cells indicate defective scaffold interactions of rescued ΔF508CFTR at the cell surface, which may contribute to its defective peripheral processing...
  98. ncbi Fluorescent indicator methods to assay functional CFTR expression in cells
    Alan S Verkman
    Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, CA, USA
    Methods Mol Med 70:187-96. 2002
  99. ncbi CFTR inhibition mimics the cystic fibrosis inflammatory profile
    Aura Perez
    Department of Pediatrics, School of Medicine, Case Western Reserve University, BRB Bldg R829, 10900 Euclid Ave, Cleveland, OH 44106 4948, USA
    Am J Physiol Lung Cell Mol Physiol 292:L383-95. 2007
    ..Our results support the hypothesis that lack of CFTR activity is responsible for the onset of the inflammatory cascade in the CF lung...
  100. ncbi Unimpaired osmotic water permeability and fluid secretion in bile duct epithelia of AQP1 null mice
    Albert Mennone
    Liver Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Am J Physiol Gastrointest Liver Physiol 283:G739-46. 2002
    ..These findings provide direct evidence that AQP1 is not rate limiting for water movement in mouse cholangiocytes and does not appear to be regulated by cyclic AMP in this species...
  101. ncbi Mucin glycosylation changes in cystic fibrosis lung disease are not manifest in submucosal gland secretions
    Benjamin L Schulz
    Proteome Systems Limited, Unit 1, 35 41 Waterloo Road, North Ryde, Sydney, NSW 2113, Australia
    Biochem J 387:911-9. 2005
    ....

Research Grants2

  1. MECHANISMS OF WATER TRANSPORT IN RENAL EPITHELIA
    Alan Verkman; Fiscal Year: 2007
    ..Methods will include fluorescence photobleaching recovery, energy transfer and ratio imaging. Also, specific water/solute transporting properties (Pd, c^)of the mammalian aquaporins will be measured. ..
  2. Application of Novel Optial Methods to Cell Dynamics
    Alan Verkman; Fiscal Year: 2007
    ..abstract_text> ..