Research Topics
Genomes and Genes
| David S WilliamsSummaryAffiliation: University of California Country: USA Publications
Research Grants
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Detail Information
Publications
Harmonin in the murine retina and the retinal phenotypes of Ush1c-mutant mice and human USH1CDavid S Williams
Jules Stein Eye Institute, Department of Ophthalmology, UCLA School of Medicine, Los Angeles, CA 90095 7008, USA
Invest Ophthalmol Vis Sci 50:3881-9. 2009..To investigate the expression of harmonin in the mouse retina, test for ultrastructural and physiological mutant phenotypes in the retina of an Ush1c mutant mouse, and define in detail the retinal phenotype in human USH1C...- The many different cellular functions of MYO7A in the retinaDavid S Williams
Department of Neurobiology and Ophthalmology, UCLA School of Medicine, Los Angeles, CA 90024, USA
Biochem Soc Trans 39:1207-10. 2011..It is likely that the progressive retinal degeneration that occurs in Usher syndrome 1B patients results from a combination of cellular defects in the RPE and photoreceptor cells... - Oxaloacetate supplementation increases lifespan in Caenorhabditis elegans through an AMPK/FOXO-dependent pathwayDavid S Williams
Departments of Pharmacology and Neurosciences, UCSD School of Medicine, University of California San Diego, La Jolla, CA 92130, USA
Aging Cell 8:765-8. 2009..These results demonstrate that supplementation of the citric acid cycle metabolite, oxaloacetate, influences a longevity pathway, and suggest a tractable means of introducing the health-related benefits of dietary restriction... - Axonal stress kinase activation and tau misbehavior induced by kinesin-1 transport defectsTomas L Falzone
Howard Hughes Medical Institute, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093, USA
J Neurosci 29:5758-67. 2009.... - Analysis of the linkage of MYRIP and MYO7A to melanosomes by RAB27A in retinal pigment epithelial cellsAdriana E Klomp
Department of Pharmacology, UCSD School of Medicine, La Jolla, CA 92093 0912, USA
Cell Motil Cytoskeleton 64:474-87. 2007..The present results provide evidence from live RPE cells that the RAB27A-MYRIP-MYO7A complex functions in melanosome motility. They also demonstrate that RAB27A provides an essential link to the melanosome... - The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65Vanda S Lopes
Jules Stein Eye Institute and Department of Neurobiology, UCLA School of Medicine, University of California Los Angeles, 200 Stein Plaza, Los Angeles, CA 90095, USA
Hum Mol Genet 20:2560-70. 2011..Together, the results support a role for MYO7A in the translocation of RPE65, illustrating the involvement of a molecular motor in the spatiotemporal organization of the retinoid cycle in vision... - Trafficking of membrane proteins to cone but not rod outer segments is dependent on heterotrimeric kinesin-IIPrachee Avasthi
Department of Ophthalmology, University of Utah Health Science Center, Salt Lake City, Utah 84132, USA
J Neurosci 29:14287-98. 2009.... - A novel allele of myosin VIIa reveals a critical function for the C-terminal FERM domain for melanosome transport in retinal pigment epithelial cellsMartin Schwander
Department of Cell Biology, Institute for Childhood and Neglected Disease, The Scripps Research Institute, La Jolla, California 92037, USA
J Neurosci 29:15810-8. 2009..Our findings also suggest that MYO7A mutations can lead to tissue-specific effects on protein levels, which may explain why some mutations in MYO7A lead to deafness without retinal impairment... - Role of myosin VIIa and Rab27a in the motility and localization of RPE melanosomesDaniel Gibbs
Department of Pharmacology, UCSD School of Medicine, La Jolla, CA 92093 0912, USA
J Cell Sci 117:6473-83. 2004..The presence of two distinct melanosome velocities in both control and Myo7a-null RPE cells suggests the involvement of at least two motors other than myosin VIIa in melanosome motility, most probably, a microtubule motor and myosin Va... - Function of MYO7A in the human RPE and the validity of shaker1 mice as a model for Usher syndrome 1BDaniel Gibbs
Department of Pharmacology, University of California at San Diego School of Medicine, La Jolla, California, USA
Invest Ophthalmol Vis Sci 51:1130-5. 2010..To investigate the function of MYO7A in human RPE cells and to test the validity of using shaker1 RPE in preclinical studies on therapies for Usher syndrome 1B by comparing human and mouse cells... - Retinal pigment epithelium defects in humans and mice with mutations in MYO7A: imaging melanosome-specific autofluorescenceDaniel Gibbs
Departments of Pharmacology, UCSD School of Medicine, La Jolla, California, USA
Invest Ophthalmol Vis Sci 50:4386-93. 2009..This study was undertaken to identify an imaging method for noninvasively monitoring the RPE component of the USH1B disease... - Analysis of kinesin-2 function in photoreceptor cells using synchronous Cre-loxP knockout of Kif3a with RHO-CreDavid Jimeno
Department of Pharmacology, University of San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA
Invest Ophthalmol Vis Sci 47:5039-46. 2006..To determine the relationship between the presence of kinesin-2 and photoreceptor cell viability and opsin transport, by generating RHO-Cre transgenic mice and breeding them to mice with a floxed kinesin-2 motor gene... - Myosin VI is required for normal retinal functionJunko Kitamoto
Department of Pharmacology, UCSD School of Medicine, La Jolla, CA 92093 0912, USA
Exp Eye Res 81:116-20. 2005..Our results indicate that myosin VI is required in photoreceptor cells for normal retinal electrophysiology... - Retinal disease course in Usher syndrome 1B due to MYO7A mutationsSamuel G Jacobson
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA
Invest Ophthalmol Vis Sci 52:7924-36. 2011.... - Amyloid precursor protein-induced axonopathies are independent of amyloid-beta peptidesGorazd B Stokin
Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, School of Medicine, University of California, San Diego, La Jolla, CA 92093 0683, USA
Hum Mol Genet 17:3474-86. 2008..Thus, we suggest that APP-induced axonal defects are not caused by Abeta... - Dysfunction of heterotrimeric kinesin-2 in rod photoreceptor cells and the role of opsin mislocalization in rapid cell deathVanda S Lopes
Departments of Ophthalmology and Neurobiology, UCLA School of Medicine, Los Angeles, CA 90095, USA
Mol Biol Cell 21:4076-88. 2010.... - Usher syndromes due to MYO7A, PCDH15, USH2A or GPR98 mutations share retinal disease mechanismSamuel G Jacobson
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
Hum Mol Genet 17:2405-15. 2008..The results point to the photoreceptor cell as the therapeutic target for USH treatment trials, such as MYO7A somatic gene replacement therapy... - Carboxypeptidase E is required for normal synaptic transmission from photoreceptors to the inner retinaXuemei Zhu
The Mary D Allen Laboratory for Vision Research, Doheny Eye Institute, and Departmentsof Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California 90033, USA
J Neurochem 95:1351-62. 2005..These results suggest that CPE is required for normal-sized photoreceptor synaptic terminal and normal signal transmission to the inner retina... - Cone-like morphological, molecular, and electrophysiological features of the photoreceptors of the Nrl knockout mouseLauren L Daniele
F M Kirby Center for Molecular Ophthalmology, Department of Ophthalmology, School of Medicine, University of Pennsylvania, Philadelphia, 19104, USA
Invest Ophthalmol Vis Sci 46:2156-67. 2005..To test the hypothesis that Nrl(-)(/)(-) photoreceptors are cones, by comparing them with WT rods and cones using morphological, molecular, histochemical, and electrophysiological criteria... - Mouse models for Usher syndrome 1BConcepcion Lillo
Department of Pharmacology, UCSD School of Medicine, La Jolla, CA 92093-0983, USA
Adv Exp Med Biol 533:143-50. 2003..In any case, it is argued that shaker1 mice are a useful model for testing USH1B gene therapy, due to the presence of mutant phenotypes other than photoreceptor cell death... - Proteomic analysis of mature melanosomes from the retinal pigmented epitheliumSassan M Azarian
Department of Pharmacology, UCSD School of Medicine, La Jolla, California 92093-0912, USA
J Proteome Res 5:521-9. 2006.... - Ciliary transport of opsinDeepti Trivedi
Jules Stein Eye Institute, University of California, Los Angeles, CA 90095, USA
Adv Exp Med Biol 664:185-91. 2010..Due to the remarkable conservation of ciliary protein function, this system of Rho-Egfp transfected hTERT-RPE1 cells provides a valid model with which to study the ciliary transport of opsin directly in live cells... - Differential spatial and temporal phosphorylation of the visual receptor, rhodopsin, at two primary phosphorylation sites in mice exposed to lightRyan A Adams
Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0640, USA
Biochem J 374:537-43. 2003..Our results are consistent with light triggering rapid priming phosphorylations of rhodopsin by rhodopsin kinase, followed by a slower phosphorylation on Ser(334), which is regulated by protein kinase C... - Molecular signature of primary retinal pigment epithelium and stem-cell-derived RPE cellsJo Ling Liao
Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
Hum Mol Genet 19:4229-38. 2010..These results establish a panel of molecular markers for evaluating the fidelity of human pluripotent stem cell to RPE conversion. This study contributes to our understanding of the utility of hESC/hiPSC-derived RPE in AMD therapy... - Analysis of the rate of disk membrane digestion by cultured RPE cellsTanja Diemer
Department of Pharmacology, UCSD School of Medicine, La Jolla, California 92093-0983, USA
Adv Exp Med Biol 613:321-6. 2008 - Usher syndrome: animal models, retinal function of Usher proteins, and prospects for gene therapyDavid S Williams
Departments of Pharmacology and Neurosciences, UCSD School of Medicine, Mail Code 0912, 9500 Gilman Drive, La Jolla, CA 92093 0912, USA
Vision Res 48:433-41. 2008..Progress in this treatment approach has been achieved by correction of mutant phenotypes in Myo7a-null mouse retinas, following lentiviral delivery of MYO7A... - Axonopathy and transport deficits early in the pathogenesis of Alzheimer's diseaseGorazd B Stokin
Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine, School of Medicine, University of California San Diego UCSD, 9500 Gilman Drive, La Jolla, CA 92093, USA
Science 307:1282-8. 2005..Reductions in microtubule-dependent transport may stimulate proteolytic processing of beta-amyloid precursor protein, resulting in the development of senile plaques and Alzheimer's disease... - Functional and morphological analysis of the subretinal injection of retinal pigment epithelium cellsMaren Engelhardt
Department of Ophthalmology, Jules Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA
Vis Neurosci 29:83-93. 2012.... - Toxicity of familial ALS-linked SOD1 mutants from selective recruitment to spinal mitochondriaJian Liu
Ludwig Institute for Cancer Research, Department of Neurosciences, Medicine, and Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Neuron 43:5-17. 2004..These findings implicate damage from action of spinal cord-specific factors that recruit mutant SOD1 to spinal mitochondria as the basis for their selective toxicity in ALS... - Cadherin 23 is a component of the tip link in hair-cell stereociliaJan Siemens
The Scripps Research Institute, Department of Cell Biology, Institute for Childhood and Neglected Disease, La Jolla, California 92037, USA
Nature 428:950-5. 2004..Moreover, CDH23 forms a complex with myosin-1c, the only known component of the mechanotransduction apparatus, suggesting that CDH23 and myosin-1c cooperate to regulate the activity of mechanically gated ion channels in hair cells... - AHI1 is required for photoreceptor outer segment development and is a modifier for retinal degeneration in nephronophthisisCarrie M Louie
Howard Hughes Medical Institute, Department of Pediatrics, University of California, San Diego, La Jolla, USA
Nat Genet 42:175-80. 2010..Our data support context-specific roles for AHI1 as a contributor to retinopathy and show that AHI1 may explain a proportion of the variability in retinal phenotypes observed in nephronophthisis... - Transport to the photoreceptor outer segment by myosin VIIa and kinesin IIDavid S Williams
Department of Pharmacology, University of California, School of Medicine, Mail Code 0983, 9500 Gilman Drive, La Jolla, CA 92093 0983, USA
Vision Res 42:455-62. 2002..Given the velocities measured for these motors in vitro, it is predicted that the resulting concentration of opsin in the plasma membrane of the connecting cilium is surprisingly low... - Elevated PGC-1? Activity Sustains Mitochondrial Biogenesis and Muscle Function without Extending Survival in a Mouse Model of Inherited ALSSandrine Da Cruz
Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Cell Metab 15:778-86. 2012..Therefore, muscle is not a primary target of mutant SOD1-mediated toxicity, but drugs increasing PGC-1? activity in muscle represent an attractive therapy for maintaining muscle function during progression of ALS... - Isolation and culture of primary mouse retinal pigmented epithelial cellsDaniel Gibbs
Department of Pharmacology, UCSD School of Medicine, La Jolla, CA 92039-0983, USA
Adv Exp Med Biol 533:347-52. 2003 - Actin-based motor properties of native myosin VIIaIgor P Udovichenko
Department of Pharmacology, UCSD School of Medicine, La Jolla, California 92093 0983, USA
J Cell Sci 115:445-50. 2002..In a sliding filament motility assay, myosin VIIa moved actin filaments with a velocity of 190 nm s(-1). These results demonstrate that myosin VIIa is a calmodulin-binding protein and a bona fide actin-based motor...
Research Grants
- KINESIN IN PHOTORECEPTOR CELLSDavid Williams; Fiscal Year: 2004..Photoreceptor degeneration, which is caused by mutations in a variety of different genes (many yet to be identified), is a major cause of human blindness. ..
- Retinal Cell Biology of Usher 1 ProteinsDavid Williams; Fiscal Year: 2007..These studies will provide new information on the retinal function of myosin VIIa, and help elucidate the basis of retinal disease in USH1B. ..
- Kinesin in photoreceptors cellsDavid Williams; Fiscal Year: 2009..The results of these studies will lead to a better understanding of critical cellular processes in the photoreceptor cilium, and thus provide important new insight into a major group of inherited retinal degenerations. ..
- RPE Cell Biology of Myosin VIIaDavid Williams; Fiscal Year: 2009..These studies should greatly enhance our understanding of the function of MYO7A, and the underlying cellular basis of retinal defects which are associated with Usher 1B. ..
- RPE Cell Biology of Myosin VIIaDavid S Williams; Fiscal Year: 2010..These studies should greatly enhance our understanding of the function of MYO7A, and the underlying cellular basis of retinal defects which are associated with Usher 1B. ..
- CELLULAR PROCESSES IN PHOTORECEPTOR CELLSDavid Williams; Fiscal Year: 2003....
- Kinesin in photoreceptors cellsDavid S Williams; Fiscal Year: 2010..The results of these studies will lead to a better understanding of critical cellular processes in the photoreceptor cilium, and thus provide important new insight into a major group of inherited retinal degenerations. ..