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Pamela Maher


Ph.D. in Biochemistry, Department of Biochemistry, University of British Columbia, 1980

Current position

Senior Staff Scientist, Cellular Neurobiology, The Salk Institute for Biological Studies, La Jolla, CA, USA

Publications (since 2005)

  1. Currais, A., Prior, M., Dargusch, R., Armando, A., Ehren, J., Schubert, D., Quehenberger, O. and Maher, P. (2013). Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer's disease transgenic mice. Aging Cell.
  2. Lewerenz, J., Baxter, P., Kassubek, R., Albrecht, P., Van Liefferinge, J., Westhoff, M. A., Halatsch, M. E., Meakin, P. J., Karpel-Massler, G., Hayes, J. D., Aronica, E., Smolders, I., Ludolph, A., Methner, A., Massie, A., Hardingham, G. E. and Maher, P. (2013). Phosphoinositide 3-kinases upregulate system xc- via eIF2alpha and ATF4 - a pathway active in glioblastomas and epilepsy. Antioxid Redox Signal.
  3. Valera, E., Dargusch, R., Maher, P. A. and Schubert, D. (2013). Modulation of 5-lipoxygenase in proteotoxicity and Alzheimer's disease. J Neurosci 33(25): 10512-10525.
  4. Ehren, J. L. and Maher, P. (2013). Concurrent regulation of the transcription factors Nrf2 and ATF4 mediates the enhancement of glutathione levels by the flavonoid fisetin. Biochem Pharmacol 85(12): 1816-1826.
  5. Albrecht, P., Henke, N., Tien, M. L., Issberner, A., Bouchachia, I., Maher, P., Lewerenz, J. and Methner, A. (2013). Extracellular cyclic GMP and its derivatives GMP and guanosine protect from oxidative glutamate toxicity. Neurochem Int 62(5): 610-619.
  6. Henke, N., Albrecht, P., Bouchachia, I., Ryazantseva, M., Knoll, K., Lewerenz, J., Kaznacheyeva, E., Maher, P. and Methner, A. (2013). The plasma membrane channel ORAI1 mediates detrimental calcium influx caused by endogenous oxidative stress. Cell Death Dis 4: e470.
  7. Currais, A. and Maher, P. (2013). Functional consequences of age-dependent changes in glutathione status in the brain. Antioxid Redox Signal 19(8): 813-822.
  8. Lewerenz, J., Hewett, S. J., Huang, Y., Lambros, M., Gout, P. W., Kalivas, P. W., Massie, A., Smolders, I., Methner, A., Pergande, M., Smith, S. B., Ganapathy, V. and Maher, P. (2013). The cystine/glutamate antiporter system x(c)(-) in health and disease: from molecular mechanisms to novel therapeutic opportunities. Antioxid Redox Signal 18(5): 522-555.
  9. Schubert, D. and Maher, P. (2012). An alternative approach to drug discovery for Alzheimer's disease dementia. Future Med Chem 4(13): 1681-1688.
  10. Lewerenz, J., Maher, P. and Methner, A. (2012). Regulation of xCT expression and system x (c) (-) function in neuronal cells. Amino Acids 42(1): 171-179.
  11. Morrison, B. E., Marcondes, M. C., Nomura, D. K., Sanchez-Alavez, M., Sanchez-Gonzalez, A., Saar, I., Kim, K. S., Bartfai, T., Maher, P., Sugama, S. and Conti, B. (2012). Cutting edge: IL-13Ralpha1 expression in dopaminergic neurons contributes to their oxidative stress-mediated loss following chronic peripheral treatment with lipopolysaccharide. J Immunol 189(12): 5498-5502.
  12. Currais, A., Prior, M., Lo, D., Jolivalt, C., Schubert, D. and Maher, P. (2012). Diabetes exacerbates amyloid and neurovascular pathology in aging-accelerated mice. Aging Cell 11(6): 1017-1026.
  13. Albrecht, P., Bouchachia, I., Goebels, N., Henke, N., Hofstetter, H. H., Issberner, A., Kovacs, Z., Lewerenz, J., Lisak, D., Maher, P., Mausberg, A. K., Quasthoff, K., Zimmermann, C., Hartung, H. P. and Methner, A. (2012). Effects of dimethyl fumarate on neuroprotection and immunomodulation. J Neuroinflammation 9: 163.
  14. Herrera, F., Maher, P. and Schubert, D. (2012). c-Jun N-terminal kinase controls a negative loop in the regulation of glial fibrillary acidic protein expression by retinoic acid. Neuroscience 208: 143-149.
  15. Maher, P. (2012). Methylglyoxal, advanced glycation end products and autism: is there a connection? Med Hypotheses 78(4): 548-552.
  16. Gelderblom, M., Leypoldt, F., Lewerenz, J., Birkenmayer, G., Orozco, D., Ludewig, P., Thundyil, J., Arumugam, T. V., Gerloff, C., Tolosa, E., Maher, P. and Magnus, T. (2012). The flavonoid fisetin attenuates postischemic immune cell infiltration, activation and infarct size after transient cerebral middle artery occlusion in mice. J Cereb Blood Flow Metab 32(5): 835-843.
  17. Chiruta, C., Schubert, D., Dargusch, R. and Maher, P. (2012). Chemical modification of the multitarget neuroprotective compound fisetin. J Med Chem 55(1): 378-389.
  18. Lewerenz, J., Sato, H., Albrecht, P., Henke, N., Noack, R., Methner, A. and Maher, P. (2012). Mutation of ATF4 mediates resistance of neuronal cell lines against oxidative stress by inducing xCT expression. Cell Death Differ 19(5): 847-858.
  19. Lewerenz, J. and Maher, P. (2011). Control of redox state and redox signaling by neural antioxidant systems. Antioxid Redox Signal 14(8): 1449-1465.
  20. Chen, Q., Prior, M., Dargusch, R., Roberts, A., Riek, R., Eichmann, C., Chiruta, C., Akaishi, T., Abe, K., Maher, P. and Schubert, D. (2011). A novel neurotrophic drug for cognitive enhancement and Alzheimer's disease. PLoS One 6(12): e27865.
  21. Lapchak, P. A., Schubert, D. R. and Maher, P. A. (2011). De-Risking of Stilbazulenyl Nitrone (STAZN), a Lipophilic Nitrone to Treat Stroke Using a Unique Panel of In Vitro Assays. Transl Stroke Res 2(2): 209-217.
  22. Maher, P., Dargusch, R., Ehren, J. L., Okada, S., Sharma, K. and Schubert, D. (2011). Fisetin lowers methylglyoxal dependent protein glycation and limits the complications of diabetes. PLoS One 6(6): e21226.
  23. Lapchak, P. A., Schubert, D. R. and Maher, P. A. (2011). Delayed treatment with a novel neurotrophic compound reduces behavioral deficits in rabbit ischemic stroke. J Neurochem 116(1): 122-131.
  24. Maher, P., Dargusch, R., Bodai, L., Gerard, P. E., Purcell, J. M. and Marsh, J. L. (2011). ERK activation by the polyphenols fisetin and resveratrol provides neuroprotection in multiple models of Huntington's disease. Hum Mol Genet 20(2): 261-270.
  25. Albrecht, P., Lewerenz, J., Dittmer, S., Noack, R., Maher, P. and Methner, A. (2010). Mechanisms of oxidative glutamate toxicity: the glutamate/cystine antiporter system xc- as a neuroprotective drug target. CNS Neurol Disord Drug Targets 9(3): 373-382.
  26. Madonna, S., Maher, P. and Kraus, J. L. (2010). N,N-Bis-(8-hydroxyquinoline-5-yl methyl)-benzyl substituted amines (HQNBA): peroxisome proliferator-activated receptor (PPAR-gamma) agonists with neuroprotective properties. Bioorg Med Chem Lett 20(23): 6966-6968.
  27. Lewerenz, J., Dargusch, R. and Maher, P. (2010). Lactacidosis modulates glutathione metabolism and oxidative glutamate toxicity. J Neurochem 113(2): 502-514.
  28. Biraboneye, A. C., Madonna, S., Maher, P. and Kraus, J. L. (2010). Neuroprotective effects of N-alkyl-1,2,4-oxadiazolidine-3,5-diones and their corresponding synthetic intermediates N-alkylhydroxylamines and N-1-alkyl-3-carbonyl-1-hydroxyureas against in vitro cerebral ischemia. ChemMedChem 5(1): 79-85.
  29. Maher, P. (2010). Modulation of multiple pathways involved in the maintenance of neuronal function by fisetin. In Micronutrients and Brain Health. L. Packer, H. Sies, M. Eggersdorfer and E. Cadenas (Eds.) CCC press, Boca Raton, FL, pp. 189-206.
  30. Maher, P., Akaishi, T., Schubert, D. and Abe, K. (2010). A pyrazole derivative of curcumin enhances memory. Neurobiol Aging 31(4): 706-709.
  31. Lewerenz, J., Albrecht, P., Tien, M. L., Henke, N., Karumbayaram, S., Kornblum, H. I., Wiedau-Pazos, M., Schubert, D., Maher, P. and Methner, A. (2009). Induction of Nrf2 and xCT are involved in the action of the neuroprotective antibiotic ceftriaxone in vitro. J Neurochem 111(2): 332-343.
  32. Biraboneye, A. C., Madonna, S., Laras, Y., Krantic, S., Maher, P. and Kraus, J. L. (2009). Potential neuroprotective drugs in cerebral ischemia: new saturated and polyunsaturated lipids coupled to hydrophilic moieties: synthesis and biological activity. J Med Chem 52(14): 4358-4369.
  33. Herrera, F., Chen, Q., Fischer, W. H., Maher, P. and Schubert, D. R. (2009). Synaptojanin-1 plays a key role in astrogliogenesis: possible relevance for Down's syndrome. Cell Death Differ 16(6): 910-920.
  34. Schubert, D., Herrera, F., Cumming, R., Read, J., Low, W., Maher, P. and Fischer, W. H. (2009). Neural cells secrete a unique repertoire of proteins. J Neurochem 109(2): 427-435.
  35. Johnson, J., Maher, P. and Hanneken, A. (2009). The flavonoid, eriodictyol, induces long-term protection in ARPE-19 cells through its effects on Nrf2 activation and phase 2 gene expression. Invest Ophthalmol Vis Sci 50(5): 2398-2406.
  36. Lewerenz, J. and Maher, P. (2009). Basal levels of eIF2alpha phosphorylation determine cellular antioxidant status by regulating ATF4 and xCT expression. J Biol Chem 284(2): 1106-1115.
  37. Maher, P. (2009). Modulation of multiple pathways involved in the maintenance of neuronal function during aging by fisetin. Genes Nutr 4(4): 297-307.
  38. Maher, P. A. and Schubert, D. R. (2009). Metabolic links between diabetes and Alzheimer's disease. Expert Rev Neurother 9(5): 617-630.
  39. Maher, P., Lewerenz, J., Lozano, C. and Torres, J. L. (2008). A novel approach to enhancing cellular glutathione levels. J Neurochem 107(3): 690-700.
  40. Maher, P. and Hanneken, A. (2008). Regulation of neural gene transcription by flavonoids. In Polyphenols and Health: New and Recent Advances. N. Vassallo (Ed.) Nova Science, New York, pp. 167-188.
  41. Maher, P. (2008). The flavonoid fisetin promotes nerve cell survival from trophic factor withdrawal by enhancement of proteasome activity. Arch Biochem Biophys 476(2): 139-144.
  42. Maher, P. (2008). Proteasome inhibitors prevent oxidative stress-induced nerve cell death by a novel mechanism. Biochem Pharmacol 75(10): 1994-2006.
  43. Liu, Y., Dargusch, R., Maher, P. and Schubert, D. (2008). A broadly neuroprotective derivative of curcumin. J Neurochem 105(4): 1336-1345.
  44. Maher, P. and Hanneken, A. (2008). Flavonoids protect retinal ganglion cells from ischemia in vitro. Exp Eye Res 86(2): 366-374.
  45. Burdo, J., Schubert, D. and Maher, P. (2008). Glutathione production is regulated via distinct pathways in stressed and non-stressed cortical neurons. Brain Res 1189: 12-22.
  46. Stachowiak, M. K., Maher, P. A. and Stachowiak, E. K. (2007). Integrative nuclear signaling in cell development--a role for FGF receptor-1. DNA Cell Biol 26(12): 811-826.
  47. Lapchak, P. A., Maher, P., Schubert, D. and Zivin, J. A. (2007). Baicalein, an antioxidant 12/15-lipoxygenase inhibitor improves clinical rating scores following multiple infarct embolic strokes. Neuroscience 150(3): 585-591.
  48. Maher, P., Salgado, K. F., Zivin, J. A. and Lapchak, P. A. (2007). A novel approach to screening for new neuroprotective compounds for the treatment of stroke. Brain Res 1173: 117-125.
  49. Maher, P. (2006). Redox control of neural function: background, mechanisms, and significance. Antioxid Redox Signal 8(11-12): 1941-1970.
  50. Maher, P. (2006). A comparison of the neurotrophic activities of the flavonoid fisetin and some of its derivatives. Free Radic Res 40(10): 1105-1111.
  51. Maher, P., Akaishi, T. and Abe, K. (2006). Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory. Proc Natl Acad Sci U S A 103(44): 16568-16573.
  52. Dunham-Ems, S. M., Pudavar, H. E., Myers, J. M., Maher, P. A., Prasad, P. N. and Stachowiak, M. K. (2006). Factors controlling fibroblast growth factor receptor-1's cytoplasmic trafficking and its regulation as revealed by FRAP analysis. Mol Biol Cell 17(5): 2223-2235.
  53. Klejbor, I., Myers, J. M., Hausknecht, K., Corso, T. D., Gambino, A. S., Morys, J., Maher, P. A., Hard, R., Richards, J., Stachowiak, E. K. and Stachowiak, M. K. (2006). Fibroblast growth factor receptor signaling affects development and function of dopamine neurons - inhibition results in a schizophrenia-like syndrome in transgenic mice. J Neurochem 97(5): 1243-1258.
  54. Hanneken, A., Lin, F. F., Johnson, J. and Maher, P. (2006). Flavonoids protect human retinal pigment epithelial cells from oxidative-stress-induced death. Invest Ophthalmol Vis Sci 47(7): 3164-3177.
  55. Maher, P. (2005). The effects of stress and aging on glutathione metabolism. Ageing Res Rev 4(2): 288-314.
  56. Maher, P. and Hanneken, A. (2005). Flavonoids protect retinal ganglion cells from oxidative stress-induced death. Invest Ophthalmol Vis Sci 46(12): 4796-4803.
  57. Torres, J. L., Lozano, C. and Maher, P. (2005). Conjugation of catechins with cysteine generates antioxidant compounds with enhanced neuroprotective activity. Phytochemistry 66(17): 2032-2037.
  58. Conti, B., Sugama, S., Lucero, J., Winsky-Sommerer, R., Wirz, S. A., Maher, P., Andrews, Z., Barr, A. M., Morale, M. C., Paneda, C., Pemberton, J., Gaidarova, S., Behrens, M. M., Beal, F., Sanna, P. P., Horvath, T. and Bartfai, T. (2005). Uncoupling protein 2 protects dopaminergic neurons from acute 1,2,3,6-methyl-phenyl-tetrahydropyridine toxicity. J Neurochem 93(2): 493-501.
  59. Maher, P. and Hanneken, A. (2005). The molecular basis of oxidative stress-induced cell death in an immortalized retinal ganglion cell line. Invest Ophthalmol Vis Sci 46(2): 749-757.
Protocols by Pamela Maher
  1. Proteasome Assay in Cell Lysates