William Mobley, MD 

William Mobley, MD, PhD 

Department Chair and Professor

 

Contact Information

Center for Neural Circuits and Behavior, Room 100

Email: wmobley@ucsd.edu
Phone: 858-534-9434
Fax: 858-534-8980

Mailing Address:
9500 Gilman Drive # 0752
La Jolla, CA 92093-0752

Lab Website


William C. Mobley is a Distinguished Professor and Chair of the Department of Neurosciences at UCSD. He also serves as Executive Director of UCSD's Down Syndrome Center for Research and Treatment. and the Florence Riford Chair of Alzheimer Disease Research. 

He 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 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 earned his Ph.D. from Stanford in Neuro- & Behavioral Science in 1974, and an M.D. from the same institution in 1976. After completing his M.D., Dr. Mobley completed an internship in pathology in 1977, also at Stanford University. He then went on to complete a residency and fellowship in neurology and pediatric neurology at The Johns Hopkins University in 1982. While there he was selected to serve as Chief Resident in Pediatric Neurology from 1981 to 1982. In 1983, he became certified by the American Board of Pediatrics and in 1987 was certified by the American Board of Psychiatry and Neurology with Special Competence in Child Neurology.

Dr. Mobley's research focuses on the neurobiology of neurotrophic factor actions and signaling and on the hypothesis that dysfunction of such signaling mechanisms contributes to neuronal dysfunction in developmental and age-related disorders of the nervous system. His emphasis on the neurobiology of Down syndrome has brought new insights into the condition, including possible treatments. He has also done pioneering work on the neurobiology of Alzheimer's disease (AD) using a mouse model of Down syndrome. These studies were based on the observation that virtually all adults with Down syndrome develop Alzheimer's disease pathology by age 40 and half develop dementia by 50. This knowledge paved the way for Dr. Mobley's ongoing studies of AD in experimental models.

Dr. Mobley has received many awards and distinctions. He is a member of the Institute of Medicine, National Academy of Sciences. He collaborated with the Dalai Lama to create the Center for Compassion and Altruism Research and Education at Stanford University. He also serves as the expert advisor to the Congressional Down Syndrome Caucus (for which he won the Christian Pueschel Memorial Award in 2007).

He 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.

In 2011 Dr. Mobley was honored with the International Sisley-Jérôme Lejeune Prize in Paris by the Jérôme Lejeune Foundation for his contributions to the field of Down syndrome and genetic intellectual disabilities. This led to his recognition by U.S. Rep. Pete Sessions on the floor of the House of Representatives. Read more.


Watch a video on UCSD-TV with Dr. Mobley on the translation gap and his research on Down syndrome and Alzheimer's disease.

Watch a UCTV program with Dr. Mobley presenting an overview of Alzheimer's disease.

Read a story about Dr. Mobley in Nebraska Magazine.

Read an article by Dr. Mobley about the connection between Down syndrome and Alzheimer's disease in the San Diego Union Tribune.

Dr. Mobley's research focuses on the neurobiology of neurotrophic factor actions and signaling and on the hypothesis that dysfunction of such signaling mechanisms contributes to neuronal dysfunction in developmental and age-related disorders of the nervous system. His emphasis on the neurobiology of Down syndrome has brought new insights into the disease, including possible treatments. He has also done pioneering work on the neurobiology of Alzheimer's Disease (AD) using a mouse model of Down syndrome (DS). These studies were based on the observation that virtually all adults with Down syndrome develop the pathology of Alzheimer's disease by the age of 50. This knowledge paved the way for Dr. Mobley's ongoing studies of AD in experimental models.

Dr. Mobley's laboratory has pursued two major themes. The first is the biology and signaling of neurotrophic factors. The second, propelled by the first, is the pathogenesis of developmental and age-related neurodegeneration in DS and AD. The Mobley Laboratory has made many important contributions to neuroscience investigation, all of which relate to the biology of neurotrophic factors or to the pathogenesis of DS. Three of these will be summarized here.

The first contribution, made in studies on nerve growth factor (NGF), was the demonstration that a neurotrophic factor acts in the central nervous system (CNS). Indeed, the lab is credited with having been among the very first to demonstrate this and to show that neurotrophic factors play similar roles in the CNS as in the Peripheral Nervous System (PNS). This contribution helped drive the search for other CNS neurotrophic factors, a search that defined the existence of many families of such factors. His lab was also among the first to point to a potential role for neurotrophic factors in the pathogenesis of neurodegeneration, a theme many labs have taken up and has prompted many attempts to treat patients with such disorders.

The second was the discovery of the "signaling endosome," the organelle through which NGF and other neurotrophic factors signal retrogradely in axons from targets. The isolation and characterization of the signaling endosome provided an important new vista on the cellular basis of signaling, making it clear how signals could be sent with high fidelity for many hours over long distances. This work stimulated others to focus on the biological significance of the spatial localization of signaling in neurons and other cells. In recent work, the Mobley Laboratory has engaged in single molecule studies to decipher in detail how the signaling endosome is created and how it enables the matching of targets of innervation with their presynaptic inputs.

The third contribution involves the pathogenesis of developmental and age-related cognitive deficits in people with DS. The Mobley laboratory has played a central role in defining the neurobiology of DS. It has shown that genetic dissection, in parallel with studies of mechanism, can be used to decipher the basis for cognitive phenotypes and for identifying potential therapeutic targets. The laboratory was the first to show that even in the context of a complex genetic disorder a single gene for Amyloid Precursor Protein (APP) plays a conspicuous role in age-related pathogenesis. The gene for APP, and the endosomal dysregulation that occurs as a result of increased expression of this gene, are now potential targets for treating age-related neurodegeneration of hippocampal afferents. Another success has been in defining dysregulation of inhibitory neurotransmission, which led to defining both GABA A and B receptors and inwardly rectifying potassium channels downstream from GABA B receptors, as playing an important role in developmental events. The gene(s) that are critical for this aspect of pathogenesis are the topic of continuing studies.

To date, Dr. Mobley has published almost 150 research articles and reviews in peer reviewed journals. Publications appear in high quality journals, such J. Neuroscience, Neurobiol Dis., and J. Comp Neurol. In addition, Dr. Mobley is co-editor of one book and has contributed to 13 books or book chapters.

Soluble γ-Secretase Modulators Selectively Inhibit the Production of the 42-Amino Acid Amyloid β Peptide Variant and Augment the Production of Multiple Carboxy-Truncated Amyloid β Species.
Wagner SL, Zhang C, Cheng S, Nguyen P, Zhang X, Rynearson KD, Wang R, Li Y, Sisodia SS, Mobley WC, Tanzi RE.
Biochemistry
Publish date: 2014 Jan 22. [Epub ahead of print]
PMID: 24401146

The challenge of connecting the dots in the B.R.A.I.N.
Devor A, Bandettini PA, Boas DA, Bower JM, Buxton RB, Cohen LB, Dale AM, Einevoll GT, Fox PT, Franceschini MA, Friston KJ, Fujimoto JG, Geyer MA, Greenberg JH, Halgren E, Hämäläinen MS, Helmchen F, Hyman BT, Jasanoff A, Jernigan TL, Judd LL, Kim SG, Kleinfeld D, Kopell NJ, Kutas M, Kwong KK, Larkum ME, Lo EH, Magistretti PJ, Mandeville JB, Masliah E, Mitra PP, Mobley WC, Moskowitz MA, Nimmerjahn A, Reynolds JH, Rosen BR, Salzberg BM, Schaffer CB, Silva GA, So PT, Spitzer NC, Tootell RB, Van Essen DC, Vanduffel W, Vinogradov SA, Wald LL, Wang LV, Weber B, Yodh AG.
Neuron.
Publish Date: Oct 2013
PMID: 24139032

Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction by modulating glutamate receptor recycling in Down's syndrome.
Wang X, Zhao Y, Zhang X, Badie H, Zhou Y, Mu Y, Loo LS, Cai L, Thompson RC, Yang B, Chen Y, Johnson PF, Wu C, Bu G, Mobley WC, Zhang D, Gage FH, Ranscht B, Zhang YW, Lipton SA, Hong W, Xu H.
Nat Med.
Publish Date: Apr 2013
PMID: 23524343

Human chromosome 21 orthologous region on mouse chromosome 17 is a major.
Zhang L, Meng K,  Liu C, Pao A, Belichenko PV, Kleschevnikov AM, Josselyn S, Liang P, Ye P, Mobley WC, Yu YE. 
Publish Date: 2013 Sep 25
PMID: 24041763

Aging and intellectual disability: Insights from mouse models of down syndrome.
Ruparelia A, Pearn ML, Mobley WC.
Dev Disabil Res
Publish Date: Aug 2013
PMID: 23949828

Illicium sesquiterpenes: divergent synthetic strategy and neurotrophic activity studies.
Trzoss L, Xu J, Lacoske MH, Mobley WC, Theodorakis EA. Chemistry.
Publish Date:
May 2013
PMID: 23526661

Potential use of γ-secretase modulators in the treatment of Alzheimer disease.
Wagner SL, Tanzi RE, Mobley WC, Galasko D.
Arch Neurol.
Publish Date: Oct 2012
PMID: 22801784

Cognitive and pharmacological insights from the Ts65Dn mouse model of Down syndrome.
Ruparelia A, Pearn ML, Mobley WC.
Curr Opin Neurobiol.
Publish Date: Oct 2012
PMID: 22658745

Deficits in cognition and synaptic plasticity in a mouse model of Down syndrome ameliorated by GABAB receptor antagonists.
Kleschevnikov AM, Belichenko PV, Faizi M, Jacobs LF, Htun K, Shamloo M, Mobley WC.
Publish Date: 2012
PMID: 22764230

Genetic analysis of Down syndrome facilitated by mouse chromosome engineering.
Zhang L,Fu D,Belichenko PV,Liu C,Kleschevnikov AM,Pao A,Liang P,Clapcote SJ,Mobley WC,Yu YE.
Publish Date: 2012 Jan 1
PMID: 22126738

Increased efficiency of the GABAA and GABAB receptor-mediated neurotransmission in the Ts65Dn mouse model of Down syndrome.
Kleschevnikov AM,Belichenko PV,Gall J,George L,Nosheny R,Maloney MT,Salehi A,Mobley WC.
Publish Date: 2012 Feb
PMID: 22062771

Mouse models for down syndrome-associated developmental cognitive disabilities.
Liu C,Belichenko PV,Zhang L,Fu D,Kleschevnikov AM,Baldini A,Antonarakis SE,Mobley WC,Yu YE.
Publish Date: 2011
PMID: 21865664

Enantioselective synthesis of (-)-jiadifenin, a potent neurotrophic modulator.
Trzoss L,Xu J,Lacoske MH,Mobley WC,Theodorakis EA.
Publish Date: 2011 Sep 2
PMID: 21812392

Comprehensive behavioral phenotyping of Ts65Dn mouse model of Down Syndrome: activation of β1-adrenergic receptor by xamoterol as a potential cognitive enhancer.
Faizi M,Bader PL,Tun C,Encarnacion A,Kleschevnikov A,Belichenko P,Saw N,Priestley M,Tsien RW,Mobley WC,Shamloo M.
Publish Date: 2011 Aug
PMID: 21527343

Implications for treatment: GABAA receptors in aging, Down syndrome and Alzheimer's disease.
Rissman RA,Mobley WC.
Publish Date: 2011 May
PMID: 21388375

Effects of individual segmental trisomies of human chromosome 21 syntenic regions on hippocampal long-term potentiation and cognitive behaviors in mice.
Yu T,Liu C,Belichenko P,Clapcote SJ,Li S,Pao A,Kleschevnikov A,Bechard AR,Asrar S,Chen R,Fan N,Zhou Z,Jia Z,Chen C,Roder JC,Liu B,Baldini A,Mobley WC,Yu YE.
Publish Date: 2010 Dec 17
PMID: 20932954

Modulation of gamma-secretase reduces beta-amyloid deposition in a transgenic mouse model of Alzheimer's disease.
Kounnas MZ,Danks AM,Cheng S,Tyree C,Ackerman E,Zhang X,Ahn K,Nguyen P,Comer D,Mao L,Yu C,Pleynet D,Digregorio PJ,Velicelebi G,Stauderman KA,Comer WT,Mobley WC,Li YM,Sisodia SS,Tanzi RE,Wagner SL.
Publish Date: 2010 Sep 9
PMID: 20826309

Deficiencies in the region syntenic to human 21q22.3 cause cognitive deficits in mice.
Yu T,Clapcote SJ,Li Z,Liu C,Pao A,Bechard AR,Carattini-Rivera S,Matsui S,Roder JC,Baldini A,Mobley WC,Bradley A,Yu YE.
Publish Date: 2010 Jun
PMID: 20512340

Restoration of norepinephrine-modulated contextual memory in a mouse model of Down syndrome.
Salehi A,Faizi M,Colas D,Valletta J,Laguna J,Takimoto-Kimura R,Kleschevnikov A,Wagner SL,Aisen P,Shamloo M,Mobley WC.
Publish Date: 2009 Nov 18
PMID: 20368182

The 50th anniversary of the discovery of trisomy 21: the past, present, and future of research and treatment of Down syndrome.
Mégarbané A,Ravel A,Mircher C,Sturtz F,Grattau Y,Rethoré MO,Delabar JM,Mobley WC.
Publish Date: 2009 Sep
PMID: 19636252

The "Down syndrome critical region" is sufficient in the mouse model to confer behavioral, neurophysiological, and synaptic phenotypes characteristic of Down syndrome.
Belichenko NP,Belichenko PV,Kleschevnikov AM,Salehi A,Reeves RH,Mobley WC.
Publish Date: 2009 May 6
PMID: 19420260

Widespread changes in dendritic and axonal morphology in Mecp2-mutant mouse models of Rett syndrome: evidence for disruption of neuronal networks.
Belichenko PV,Wright EE,Belichenko NP,Masliah E,Li HH,Mobley WC,Francke U.
Publish Date: 2009 May 20
PMID: 19296534

Evidence for both neuronal cell autonomous and nonautonomous effects of methyl-CpG-binding protein 2 in the cerebral cortex of female mice with Mecp2 mutation.
Belichenko NP,Belichenko PV,Mobley WC.
Publish Date: 2009 Apr
PMID: 19167498

Excitatory-inhibitory relationship in the fascia dentata in the Ts65Dn mouse model of Down syndrome.
Belichenko PV,Kleschevnikov AM,Masliah E,Wu C,Takimoto-Kimura R,Salehi A,Mobley WC.
Publish Date: 2009 Feb 1
PMID: 19034952

The coming of age of axonal neurotrophin signaling endosomes.
Wu C,Cui B,He L,Chen L,Mobley WC.
Publish Date: 2009 Feb 15
PMID: 19028611

Endophilin B1 as a novel regulator of nerve growth factor/ TrkA trafficking and neurite outgrowth.
Wan J,Cheung AY,Fu WY,Wu C,Zhang M,Mobley WC,Cheung ZH,Ip NY.
Publish Date: 2008 Sep 3
PMID: 18768694

Review of the toxicology of chlorpyrifos with an emphasis on human exposure and neurodevelopment.
Eaton DL,Daroff RB,Autrup H,Bridges J,Buffler P,Costa LG,Coyle J,McKhann G,Mobley WC,Nadel L,Neubert D,Schulte-Hermann R,Spencer PS.
Publish Date: 2008
PMID: 18726789

Comparative study of brain morphology in Mecp2 mutant mouse models of Rett syndrome.
Belichenko NP,Belichenko PV,Li HH,Mobley WC,Francke U.
Publish Date: 2008 May 1
PMID: 18306326

Sleep and EEG features in genetic models of Down syndrome.
Colas D,Valletta JS,Takimoto-Kimura R,Nishino S,Fujiki N,Mobley WC,Mignot E.
Publish Date: 2008 Apr

PMID: 18282758

See more from PubMed

 

Year Award
2014

Society of Scholars
Johns Hopkins School of Medicine

2012

Health Hero
ALS Association of San Diego

2011

2011

Congressional Record, Pete Sessions (House of Representatives), Award to Dr. Mobley in recognition for his contribution to DS
International Sisley-Jérôme Lejeune Prize
Jérôme Lejeune Foundation

2007 Christian Pueschel Memorial Award for Research in Down Syndrome
National Down Syndrome Congress
2006 Fellow
American Association for the Advancement of Science
2004 Cotzias Award
American Academy of Neurology
2004 Member
Institute of Medicine, National Academy of Sciences
2003 Fellow
American College of Neuropsychopharmacology
2001 Temple Award
Alzheimer's Association
2001 Fellow
Royal College of Physicians
2001 Member
Dana Alliance
1998 Zenith Award for Research in Alzherimer's Disease
Alzheimer's Association
1997 John E Cahill Family Chair in Neurology & Neurological Sciences
1996 Kaiser Award for Excellence in Teaching
UCSF
1991 Derek Denny-Brown Neurological Scholar
American Neurological Association
1986 Basil O'Connor Award
National Foundation
1970 Phi Beta Kappa
1970 Senior Man's Honorary
Innocent's Society, University of Nebraska
1970 Highest Distinction
University of Nebraska