Pamela Maher

Senior Staff Scientist

Cellular Neurobiology Laboratory

Salk Institute for Biological Studies - Pamela Maher

Pamela Maher


Brief Description of Research

My research interests include the characterization and development of natural products for the treatment of acute and chronic neurological disorders such as Alzheimer's disease. In addition, I study models and mechanisms of neuroprotection in neurodegenerative diseases.


Education

BSc, Biochemistry, McGill University, Montreal, Quebec, Canada
PhD, Biochemistry, University of British Columbia, Vancouver, BC, Canada
Postdoc, Cell Biology, University of California, San Diego

Recent Publications:

  1. Ehren, J. L. and Maher, P. Concurrent regulation of the transcription factors Nrf2 and ATF4 mediates the enhancement of glutathione levels by the flavonoid fisetin. Biochem. Pharmacol. 85:1816-1826, 2013.
  2. Valera, E., Dargusch, R., Maher, P. A. and Schubert, D. Modulation of 5-lipoxygenase in proteotoxicity and Alzheimer’s disease. J. Neurosci. 33:10512-105125, 2013.
  3. Lewerenz, J., Baxter, P., Kassubek, R., Albrecht, P., Van Liefferinge, J., Westhoff, M. A., 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. Phosphoinositide 3-kinases upregulate system xc- via eIF2a and ATF4 – a pathway active in glioblastomas and epilepsy. Antiox. Redox Signal. 20:2907-2922, 2014.
  4. Currais, A., Prior, M., Dargusch, R., Armando, A., Ehren, J., Schubert, D., Quehenberger, O. and Maher, P. Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer’s disease transgenic mice. Aging Cell 13:379-390, 2014.
  5. Currais, A., Chiruta, C., Goujon-Svrzic, M., Costa, G., Santos, T., Batista, M.T., Paiva, J., Madureira, M.d.C., and Maher, P. Screening and identification of neuroprotective compounds relevant to Alzheimer's disease from medicinal plants of S. Tomé e Principe. J. Ethnopharmacol. 155, 830-840, 2014.
  6. Maher, P. and Kontoghiorghes, G. J. Characterization of the neuroprotective potential of derivatives of the iron chelating drug deferiprone. Neurochem. Res. 40:609-620, 2015.
  7. Dafre, A. L., Goldberg, J., Wang, T., Spiegel, D. A. and Maher, P. Methylglyoxal, the foe and friend of glyoxalase and Trx/TrxR systems in HT22 nerve cells. Free Rad. Biol. Med. 89:8-19, 2015.
  8. Krasieva, T. B., Ehren, J., O'Sullivan, T., Tromberg, B. and Maher, P. Cell and brain tissue imaging of the flavonoid fisetin using label-free two-photon microscopy. Neurochem. Int. 89:243-248, 2015.
  9. Currais, A., Goldberg, J., Farrokhi, C., Chang, M., Prior, M., Dargusch, R., Daughtery, D., Armando, A., Quehenberger, O., Maher, P. and Schubert, D. A comprehensive multiomics approach toward understanding the relationship between aging and dementia. Aging 7:937-955, 2015.
  10. McClatchy, D. B., Savas, J. N., Martinez-Bartolome, S., Park, S. K., Maher, P. , Powell, S. B. and Yates, J. R. Global quantitative analysis of the phosphorylation underlying phencyclidine signaling and sensorimotor gating in the prefrontal cortex. Mol. Psychiatry 21:205-215, 2016.
  11. Currais, A., Farrokhi, C., Dargusch, R., Goujon-Svrzic, M. and Maher, P. Dietary glycemic index modulates the behavioral and biochemical abnormalities associated with autism spectrum disorder. Mol. Psychiatry 21:426-436, 2016.
  12. Currais, A., Quehenberger, O., Armando, A, Daugherty, D., Maher, P. and Schubert, D. Amyloid proteotoxicity initiates and inflammatory response blocked by cannabinoids. NPJ Aging Mech. Dis. 2:16012, 2016.
  13. Merckx, E., Albertini, G., Paterka, M., Jensen, C., Albrecht, P., Dietrich, M., Van Liefferinge, J., Bentea, E., Verbruggen, L., Demuyser, T., Deneyer, L., Lewerenz, J., van Loo, G., De Keyset, J., Sato, H., Maher, P., Methner, A. and Massie, A. Absence of system xc- on immune cells invading the central nervous system alleviates experimental autoimmune encephalitis. J. Neuroinflamm. 14:9, 2017.
  14. Dafre, A. L., Schmitz, A. E. and Maher, P. Methylglyoxal-induced AMPK activation leads to autophagic degradation of thioredoxin 1 and glyoxalase 2 in HT22 nerve cells. Free Rad. Biol. Med. 108:270-279, 2017.
  15. Mori, S., Sugama, S., Nguyen, W., Michel, T., Sanna, M. G., Sanchez-Alavez, M., Cintron-Colon, R., Moroncini, G., Kakinuma, Y., Maher, P. and Conti, B. Lack of interleukin-13 receptor a1 delays the loss of dopminergic neurons during chronic stress. J. Neuroinflamm. 14:88, 2017.
  16. Schmitz, A. E., de Souza, L. F., Dos Santos, B., Maher, P., Lopes, F. M., Londero, G. F., Klamt, F. and Dafre, A. L. Methylglyoxal-induced protection response and toxicity: role of glutathione reductase and thioredoxin systems. Neurotox. Res., 32:340-350, 2017.
  17. Daughtery, D., Goldberg, J., Fischer, W., Dargusch, R., Maher, P. and Schubert, D. A novel Alzheimer's disease drug candidate targeting inflammation and fatty acid metabolism. Alzheimers Res. Ther. 9:50, 2017.
  18. Currais, A., Farrokhi, C. Dargusch, R., Armando, A., Quehenberger, O., Schubert, D. and Maher, P. Fisetin reduces the impact of aging on behavior and physiology in the rapidly aging SAMP8 mouse. J. Gerontol. A Biol. Sci. Med. Sci., 73:299-307, 2017.
  19. Maher, P. and Conti, B. Deciphering the pathways that protect from IL-13-mediated potentiation of oxidative stress induced nerve cell death. Cytokine, 103:114-120, 2018.
  20. Maher, P. Potentiation of glutathione loss and nerve cell death by the transition metals iron and copper: Implications for age-related neurodegenerative diseases. Free Rad. Biol. Med. 115:92-104, 2018.
  21. Schramm, S., Huang, G., Gunesch, S., Lang, F., Roa, J., Hogger, P., Sabate, R., Maher, P. and Decker, M. Regioselective synthesis of 7-O-esters of the flavnonolignan silibinin and SARs laed to compounds with overadditive neuroprotective effects. Eur. J. Med. Chem. 146:93-107, 2018.
  22. Goldberg, J., Currais, A., Prior, M., Fischer, W., Chiruta, C., Ratliff, E., Daugherty, D., Dargusch, R., Finley, K., Esparza-Molto, P. B., Cuezva, J. M., Maher, P., Petrascheck, M. and Schubert, D. The mitochondrial ATP synthase is a shared drug target for aging and dementia. Aging Cell 17:12715, 2018.
  23. Fischer, W., Currais, A., Liang, Z., Pinto, A. and Maher, P. Old age-associated phenotypic screening for Alzheimer's disease drug candidates identifies sterubin as a potent neuroprotective compound from Yerba santa. Redox Biol. 21:101089, 2019.
  24. Dafre, A.L., Schmitz, A.E. and Maher, P. Hyperosmotic stress initiates AMPK-independent autophagy and AMPK- and autophagy-independent depletion of thioredoxin 1 and glyoxalase 2 in HT22 nerve cells. Oxid. Med. Cell. Longevity, in press.

Recent Reviews and Book Chapters (* indicates peer-reviewed):

 
  1. Lewerenz, J., Hewett, S., Huang, Y., Lambros, M., Gout, P. W., Kalivas, P., Massie, A., Smolders, I., Methner, A., Pergande, M., Smith, S. B., Ganapathy, V. and Maher, P. The cystine/glutamate antiporter system xc- in health and disease:From molecular mechanisms to novel therapeutic opportunities. Antioxid. Redox Signal. 18:522-555, 2013.*
  2. Currais, A. and Maher, P. Functional consequences of age-dependent changes in glutathione status in the brain. Antioxid. Redox Signal. 19:813-822, 2013.*
  3. Prior, M., Chiruta, C., Currais, A., Goldberg, J., Dargusch, R., Maher, P., and Schubert, D. Back to the future with phenotypic screening. ACS Chemical Neuroscience 5, 503-513, 2014.*
  4. Maher, P. How fisetin reduces the impact of age and disease on CNS function. Front. Biosci. 7:58-82, 2015.*
  5. Lewerenz, J. and Maher, P. Chronic glutamate toxicity in neurodegenerative diseases-What is the evidence? Front. Neurosci. 16:469, 2015.*
  6. Maher, P. Grapes and the Brain. In Grapes and Health. J. M. Pezzuto (Ed) Springer, Switzerland, pp. 139-161, 2016.
  7. Mori. S., Maher, P., Conti, B. Neuroimmunology of the Interleukins 13 and 4. Brain Sci. 6:E18, 2016.*
  8. Currais, A., Fischer, W., Maher, P. and Schubert, D. Intraneuronal protein aggregation as a trigger for inflammation and neurodegeneration in the aging brain. FASEB J. 31:5-10, 2017.*
  9. Maher, P. Protective effects of fisetin and other berry flavonoids in Parkinson's disease. Food Func., 8:3033-3042, 2017.*
  10. Maher, P., van Leyen, K., Dey, P. N., Honrath, B., Dolga, A. and Methner, A. The role of calcium in cell death caused by oxidative glutamate toxicity and ferroptosis. Cell Calcium 70:47-55, 2018.*
  11. Lewerenz, J., Ates, G., Methner, A., Conrad, M. and Maher, P. Oxytosis/Ferroptosis-(Re-) emerging roles for oxidative stress-dependent non-apoptotic cell death in diseases of the nervous system. Front. Neurosci. 12:214, 2018.*
  12. Schubert, D., Currais, A., Goldberg, J., Finley, K., Petrascheck, M. and Maher, P. Geroneuroprotectors: Effective geroprotectors for the brain. Trends Pharmacol. Sci. 39:1004-1007, 2018.*