Lindsay Self: 734-764-4182
Areas of Interest
Vision begins when light is captured by the rod and cone-shaped outer segments of photoreceptor cells in the retina. The outer segment is the modified primary cilium and has a unique architecture: hundreds of disc-shaped membranes, tightly stacked and surrounded by a ciliary membrane. This arrangement maximizes light absorption by the GPCR photopigment, and places its signaling proteins in close proximity. A by-product of light absorption is photooxidative damage, which photoreceptors resolve by continuously replacing its outer segment by trafficking a massive quantity of new protein and lipid material to this compartment from the cell body on a daily basis. Defects in outer segment trafficking and mislocalization of proteins from the outer segment to other cellular compartments underlie many form of inherited retinal degenerative disease.
Our laboratory aims to understand the molecular and cellular mechanisms responsible for establishing and maintaining polarized localization of proteins in the outer segment and how protein and lipid transport regulate the formation of this compartment. We utilize both lower and higher vertebrate animal models, thereby taking advantage of unique methodologies applicable to each animal type. We conduct many experiments in transgenic Xenopus frogs, which have large photoreceptors that are uniquely suitable for morphological and live imaging studies. We also use the high throughput gene delivery technique of in vivo electroporation in mouse photoreceptors, which provide a wealth of genetic, imaging and biochemical tools. Elucidating the fundamental knowledge of how the outer segment is formed, populated and maintained will be paramount as the vision community begins to explore regenerative approaches to treat patients with retinal disease.
- PhD - Biochemistry and Molecular Biology, University of Louisville School of Medicine
- Postdoctoral - Duke University
- Pearring JN, Spencer WJ, Lieu EC, Arshavsky VY. (2015) Guanylate cyclase 1 relies on rhodopsin for intracellular stability and ciliary trafficking. eLife e12058. PMID: 26590321.
- Pearring JN, San Agustin JT, Lobanova ES, Gabriel CJ, Lieu EC, Monis WJ, Stuck MW, Strittmatter L, Jaber SM, Arshavsky VY, Pazour GJ. (2017) Loss of Arf4 causes severe degeneration of the exocrine pancreas but not cystic kidney disease or retinal degeneration. PLoS Genetics 13:e1006740. PMID: 28410364.
- Salinas RY*, Pearring JN*, Ding JD*, Spencer WJ, Hao Y, Arshavsky VY. (2017) Photoreceptor discs form through peripherin-dependent suppression of ciliary ectosome release. Journal of Cell Biology 216:1489-99. PMID: 28381413.