Retinal Cell Biology

David S. Williams, PhD, Director

Contact Information
Phone: (310) 825-9546
Fax: (310) 825-2224
Email: [email protected]

Location Address
Stein Eye Institute
Jules Stein Building
100 Stein Plaza, UCLA
Los Angeles, CA 90095

Research Areas

Cell biology of photoreceptors and retinal pigment epithelial cell.a
 

Description

The Retinal Cell Biology Laboratory focuses on the cell biology of photoreceptors and retinal pigment epithelial cells. Laboratory researchers are especially interested in cell biological studies of the retina in relation to retinal function and inherited retinal disease. 

Basic science investigations include identifying how proteins and organelles are transported and targeted within photoreceptors and retinal pigment epithelial cells. Photoreceptor and retinal pigment epithelial cells offer unique perspectives in cell polarization and the underlying mechanisms that are critical for establishing and maintaining polarization. Studies also include how metabolism drives cell differentiation and underlies many of the important cellular functions of the photoreceptors and retinal pigment epithelium. 

Studies on retinal disease include the use of stem cells to generate disease-in-a-dish models for Usher syndrome, choroideremia, and macular degeneration. Studies also involve cell culture and in vivo studies on gene therapy, using gene augmentation, and gene editing..

Representative Publications

BArikawa K, Molday LL, Molday RS, Williams DS. Localization of peripherin/rds in the disk membranes of cone and rod photoreceptors: relationship to disk membrane morphogenesis and retinal degeneration. J Cell Biol. 1992 Feb;116(3):659-67. doi: 10.1083/jcb.116.3.659. PMID: 1730772; PMCID: PMC2289304.

Liu X, Ondek B, Williams DS. Mutant myosin VIIa causes defective melanosome distribution in the RPE of shaker-1 mice. Nat Genet. 1998 Jun;19(2):117-8. doi: 10.1038/470. PMID: 9620764.

Marszalek JR, Liu X, Roberts EA, Chui D, Marth JD, Williams DS, Goldstein LS. Genetic evidence for selective transport of opsin and arrestin by kinesin-II in mammalian photoreceptors. Cell. 2000 Jul 21;102(2):175-87. doi: 10.1016/s0092-8674(00)00023-4. PMID: 10943838.

Stokin GB, Lillo C, Falzone TL, Brusch RG, Rockenstein E, Mount SL, Raman R, Davies P, Masliah E, Williams DS, Goldstein LS. Axonopathy and transport deficits early in the pathogenesis of Alzheimer's disease. Science. 2005 Feb 25;307(5713):1282-8. doi: 10.1126/science.1105681. PMID: 15731448. 

Jiang M, Esteve-Rudd J, Lopes VS, Diemer T, Lillo C, Rump A, Williams DS. Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis. J Cell Biol. 2015 Aug 17;210(4):595-611. doi: 10.1083/jcb.201410112. Epub 2015 Aug 10. PMID: 26261180; PMCID: PMC4539993.

Volland S, Hughes LC, Kong C, Burgess BL, Linberg KA, Luna G, Zhou ZH, Fisher SK, Williams DS. Three-dimensional organization of nascent rod outer segment disk membranes. Proc Natl Acad Sci USA. 2015 Dec 1;112(48):14870-5. doi: 10.1073/pnas.1516309112. Epub 2015 Nov 17. PMID: 26578801; PMCID: PMC4672767.

Esteve-Rudd J, Hazim RA, Diemer T, Paniagua AE, Volland S, Umapathy A, Williams DS. Defective phagosome motility and degradation in cell nonautonomous RPE pathogenesis of a dominant macular degeneration. Proc Natl Acad Sci U S A. 2018 May 22;115(21):5468-5473. doi: 10.1073/pnas.1709211115. Epub 2018 May 7. PMID: 29735674; PMCID: PMC6003516.

Chadha A, Paniagua AE, Williams DS. Comparison of Ciliary Targeting of Two Rhodopsin-Like GPCRs: Role of C-Terminal Localization Sequences in Relation to Cilium Type. J Neurosci. 2021 Sep 8;41(36):7514-7531. doi: 10.1523/JNEUROSCI.0357-21.2021. Epub 2021 Jul 22. PMID: 34301828; PMCID: PMC8425976.

Umapathy A, Torten G, Paniagua AE, Chung J, Tomlinson M, Lim C, Williams DS. Spatiotemporal Live-Cell Analysis of Photoreceptor Outer Segment Membrane Ingestion by the Retinal Pigment Epithelium Reveals Actin-Regulated Scission. J Neurosci. 2023 Apr 12;43(15):2653-2664. doi: 10.1523/JNEUROSCI.1726-22.2023. Epub 2023 Mar 6. PMID: 36878726; PMCID: PMC10089248.

Grants & Support

NIH-NEI National Eye Institute
Exploring the Relationship of Water Flow Across the RPE and Mutant-MYO7A/Usher 1B
01/01/2020 - 12/31/2023
$423,150.00
 

Principal Investigator