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William C. Mobley, M.D., Ph.D.

Associate Dean of Neurosciences Initiatives; Distinguished Professor of Neurosciences; Executive Director, Down Syndrome Center for Research and Treatment; Florence Riford Chair of Alzheimer’s Disease Research, University of California, San Diego

Dr. William Mobley has a distinguished record of academic achievement and is considered one of the most prominent academic neurologists in the US. He has an international reputation for his research on degenerative disease of the central nervous system as well as being a leader in translational medicine, bridging clinical and basic science.

Dr. Mobley came to UCSD in June 2009 from Stanford University in Palo Alto, Calif., where he served as the John E. Cahill Family Professor in the Department of Neurology and Neurological Sciences and was the founding director of the Neuroscience Institute. Dr. Mobley is the recipient of both the Zenith Award and the Temple Award from the Alzheimer’s Association and was chosen to receive the Cotzias Award of the American Academy of Neurology in 2004. Dr. Mobley is Past President of the Association of University Professors of Neurology, of the Professors of Child Neurology, and of the International Society for Developmental Neuroscience.  He is a Fellow of the Royal College of Physicians and in 2006 was named a Fellow of the American Association for the Advancement of Science.

Related Research:

APP Gene Dose-Mediated Dysregulation of the Endolysosomal Network Acts to Compromise Synaptic Structure and Function Leading to Alzheimer’s Disease in Down Syndrome William C. Mobley 2023-12-21 Amyloid Beta-Mediated Inhibition of Gamma-Secretase Activity Induces Alzheimer’s Disease-Relevant Cellular Phenotypes William C. Mobley Lucía Chávez-Gutiérrez 2019-01-10 Treating with Gamma-Secretase Modulators (GSMs) to Prevent Neurodegeneration in Mouse Models of Down Syndrome William C. Mobley 2018-08-09 GABAergic inhibitory efficiency and adult neurogenesis in the hippocampus of aged Ts65Dn mice, a model of ‘Alzheimer’s disease in Down syndrome’, after chronic treatment with the monoacylglycerol lipase inhibitor JZL184 William C. Mobley 2014-07-17 Effects of Inhibitors of Monoacylglycerol Lipase on Behavior and Synaptic Plasticity of Ts65Dn Mice, a Genetic Model of Down Syndrome William C. Mobley 2013-06-13 Design, Synthesis and Characterization of Novel and Potent Gamma Secretase Modulators: Physiochemical and Pharmacokinetic Properties Steven L. Wagner William C. Mobley 2011-02-12

Funded Research

These projects were made possible from Cure Alzheimer's Fund support.

Project Description Researchers Funding
APP Gene Dose-Mediated Dysregulation of the Endolysosomal Network Acts to Compromise Synaptic Structure and Function Leading to Alzheimer’s Disease in Down Syndrome 2023, 2025

$460,000
Amyloid Beta-Mediated Inhibition of Gamma-Secretase Activity Induces Alzheimer’s Disease-Relevant Cellular Phenotypes 2018, 2020

$456,475
Treating with Gamma-Secretase Modulators (GSMs) to Prevent Neurodegeneration in Mouse Models of Down Syndrome 2017 and 2019

$300,000
GABAergic inhibitory efficiency and adult neurogenesis in the hippocampus of aged Ts65Dn mice, a model of ‘Alzheimer’s disease in Down syndrome’, after chronic treatment with the monoacylglycerol lipase inhibitor JZL184 2014

$100,000
Effects of Inhibitors of Monoacylglycerol Lipase on Behavior and Synaptic Plasticity of Ts65Dn Mice, a Genetic Model of Down Syndrome 2013

$100,000
Design, Synthesis and Characterization of Novel and Potent Gamma Secretase Modulators: Physiochemical and Pharmacokinetic Properties 2009

$200,000

Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.

Flores-Aguilar, L., Hamlett, E. D., Araya, P., Barone, E., Bhattacharyya, A., ... Mobley, W. … Head, E. Imagine, Discover, Inspire: Proceedings of the 4th International Conference of the Trisomy 21 Research Society, NeuroMolecular Medicine, January 5, 2025, Read More

Zoltowska, K. M., Das, U., Lismont, S., Enzlein, T., Maesako, M., Houser, M. C. Q., Franco, M. L., Özcan, B., Gomes Moreira, D., Karachentsev, D., Becker, A., Hopf, C., Vilar, M., Berezovska, O., Mobley, W., & Chávez-Gutiérrez, L. Alzheimer’s disease linked Aβ42 exerts product feedback inhibition on γ-secretase impairing downstream cell signaling, eLife, July 19, 2024, Read More

Chen, X. Q., Becker, A., Albay, R., Nguyen, P. D., Karachentsev, D., Roberts, A. J., Rynearson, K. D., Tanzi, R. E., & Mobley, W. C. γ-Secretase Modulator BPN15606 Reduced Aβ42 and Aβ40 and Countered Alzheimer-Related Pathologies in a Mouse Model of Down Syndrome, Annals of Neurology, May 15, 2024, Read More

Johnstone, A., & Mobley, W. Local TrkB signaling: themes in development and neural plasticity, Cell and Tissue Research, September 16, 2020, Read More

Ballard, C., Mobley, W., Hardy, J., Williams, G., & Corbett, A. Dementia in Down Syndrome, Lancet Neurology, April 11, 2016, Read More

Stupack, J., Xiong, X. P., Jiang, L. L., Zhang, T., Zhou, L., Campos, A., Ranscht, B., Mobley, W., Pasquale, E. B., Xu, H., & Huang, T. Y. Soluble SORLA enhances neurite outgrowth and regeneration through activation of the EGF Receptor/ERK signaling axis, Journal of Neuroscience, June 29, 2020, Read More

Belichenko, P. V., Kleschevnikov, A. M., Becker, A., Wagner, G. E., Lysenko, L. V., Yu, Y. E., & Mobley, W. C. Down syndrome conitive phenotypes modeled in mice trisomic for all HAS 21 Homologues, PLoS One, July 31, 2015, Read More

Kleschevnikov, A. M., Yu, J., Kim, J., Lysenko, L. V., Zeng, Z., Yu, Y. E., & Mobley, W. C. Evidence that increased Kcnj6 gene dose is necessary for deficits in behavior and dentate gyrus synaptic plasticity in the Ts65Dn mouse model of Down syndrome, Neurobiology of Disease, March 22, 2017, Read More

Chen, X. Q., & Mobley, W. C. Alzheimer’s disease pathogenesis: insights from molecular and cellular biolgoy studies of oligomeric A beta and Tau species, Frontiers in Neuroscience, June 21, 2019, Read More

Chen, X. Q., & Mobley, W. C. Exploring the Pathogenesis of Alzheimer Disease in Basal Forebrain Cholinergic Neurons: Converging Insights From Alternative Hypotheses, Frontiers in Neuroscience, May 7, 2019, Read More

Bartesaghi, R., Vicari, S., & Mobley, W. C. Prenatal and Postnatal Pharmacotherapy in Down Syndrome: The Search to Prevent or Ameliorate Neurodevelopmental and Neurodegenerative Disorders, Annual Review of Pharmacology and Toxicology, January 6, 2022, Read More

Fu, X. D., & Mobley, W. C. Therapeutic Potential of PTB Inhibition Through Converting Glial Cells to Neurons in the Brain, Annual Review of Neuroscience, July 10, 2023, Read More

Snyder, H. M., Bain, L. J., Brickman, A. M., Carrillo, M. C., Esbensen, A. J., Espinosa, J. M., Fernandez, F., Fortea, J., Hartley, S. L., Head, E., Hendrix, J., Kishnani, P. S., Lai, F., Lao, P., Lemere, C., Mobley, W., Mufson, E. J., Potter, H., Zaman, S. H., Granholm, A. C., … Rafii, M. S. Further understanding the connection between Alzheimer’s disease and Down syndrome, Alzheimer's & Dementia, June 16, 2020, Read More

Chen, X. Q., Sawa, M., Becker, A., Karachentsev, D., Zuo, X., Rynearson, K. D., Tanzi, R. E., & Mobley, W. C. Retromer Proteins Reduced in Down Syndrome and the Dp16 Model: Impact of APP Dose and Preclinical Studies of a γ-Secretase Modulator, Annals of Neurology, April 11, 2023, Read More

Rynearson, K. D., Ponnusamy, M., Prikhodko, O., … Mobley, W. C., Thinakaran, G., Tanzi, R. E., Wagner, S. L. Preclinical validation of a potent γ-secretase modulator for Alzheimer’s disease prevention, Journal of Experimental Medicine, March 2, 2021, Read More

Rynearson, K. D., Buckle, R. N., Herr, R. J., Mayhew, N. J., Chen, X., Paquette, W. D., Sakwa, S. A., Yang, J., Barnes, K. D., Nguyen, P., Mobley, W. C., Johnson, G., Lin, J. H., Tanzi, R. E., & Wagner, S. L. Design and synthesis of novel methoxypyridine-derived gamma-secretase modulators, Bioorganic and Medicinal Chemistry, September 1, 2020, Read More

Wagner, S. L., Rynearson, K. D., Duddy, S. K., Zhang, C., Nguyen, P. D., Becker, A., Vo, U., Masliah, D., Monte, L., Klee, J. B., Echmalian, C. M., Xia, W., Quinti, L., Johnson, G., Lin, J. H., Kim, D. Y., Mobley, W. C., Rissman, R. A., & Tanzi, R. E. Pharmacological and Toxicological Properties of the Potent Oral gamma-secretase modulator BPN-15606, Journal of Pharmacology and Experimental Therapeutics, July 1, 2017, Read More

Weissmiller, A. M., Natera-Naranjo, O., Reyna, S. M., Pearn, M. L., Zhao, X., Nguyen, P., Cheng, S., Goldstein, L. S., Tanzi, R. E., Wagner, S. L., Mobley, W. C., & Wu, C. A gamma secretase inhibitor, but not a gamma-secretase modulator, induced defects in BDNF Axonal trafficking and signaling: evidence for a role for APP, PLoS One, February 24, 2015, Read More

Wagner, S. L., Zhang, C., Cheng, S., Nguyen, P., Zhang, X., Rynearson, K. D., Wang, R., Li, Y., Sisodia, S. S., Mobley, W. C., & Tanzi, R. E. Soluble gamma-secretase modulators slectively inhibit the production of the 42 amino-acid amyloid beta peptide variant and augment the production of multiple carboxy-truncated amyloid beta species, Biochemistry, January 22, 2014, Read More

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