Vadim Y Arshavsky

Vadim Y Arshavsky

Helena Rubinstein Foundation Distinguished Professor of Ophthalmology

External Address: 
5012 Aeri, Durham, NC 27710
Internal Office Address: 
Box 3802 Med Ctr, Durham, NC 27710
Phone: 
919.668.5391

Overview

Research conducted in our laboratory is dedicated to understanding how vision is performed on the molecular level. Our most mature direction addresses the function of rod and cone photoreceptors, which are sensory neurons responsible for the detection and primary processing of information entering the eye in the form of photons. Photoreceptors respond to capturing photons by generating electrical signals transmitted to the secondary neurons in the retina and, ultimately, to the brain. Our work is dedicated to uncovering the molecular mechanisms underlying three essential photoreceptor functions: their uniquely high light-sensitivity, their ability to rapidly recover from light excitation, and their capacity to modulate light-responses upon broad variations in the intensity of ambient illumination.

Our second direction is to elucidate the cellular processes responsible for building the light-sensitive organelle of photoreceptor cells, called the outer segment, and for populating this organelle with proteins conducting visual signaling. Of particular interest is the mechanism by which outer segments form their “disc” membrane stacks providing vast membrane surfaces for effective photon capture.

Finally, we are seeking connections between understanding the basic function of rods and cones and practical, translational approaches to ameliorate the retinal degeneration caused by mutations in critical photoreceptor-specific proteins. Most importantly, we explore the link between the balance of protein synthesis and degradation in photoreceptor cells (the “proteostasis”) and the status of their health.

Education & Training

  • Ph.D., Lomonosov Moscow State Universty (Russia) 1987

  • B.S., Lomonosov Moscow State Universty (Russia) 1981

Selected Grants

Center Core Grant for Vision Research awarded by National Institutes of Health (Principal Investigator). 2001 to 2026

Cell and Molecular Biology Training Program awarded by National Institutes of Health (Mentor). 2021 to 2026

Pharmacological Sciences Training Grant awarded by National Institutes of Health (Preceptor). 2020 to 2025

Mechanisms of photoreceptor disc maturation awarded by National Institutes of Health (Principal Investigator). 2020 to 2025

Molecular mechanisms of photoreceptor outer segment morphogenesis awarded by National Institutes of Health (Principal Investigator). 2005 to 2023

In Vivo Modeling of Mitochondrial Complex I Deficiency in Retinal Ganglion Cells awarded by National Institutes of Health (Mentor). 2018 to 2023

Gene therapy treatment of neurodegeneration using proteasome activators awarded by Sio Gene Therapies (Principal Investigator). 2021 to 2022

Understanding the roles of ectosomes and the associated microglial response in photoreceptor degeneration awarded by Knights Templar Eye Foundation, Inc. (Principal Investigator). 2021 to 2022

Pathological and functional consequences of dimerization-deficient rhodopsin mutations awarded by National Institutes of Health (Principal Investigator). 2019 to 2022

Mechanisms of photoreceptor protein transport and compartmentalization awarded by SUNY Upstate Medical University (Principal Investigator). 2021

Pages

Herrmann, R., and V. Y. Arshavsky. “The role of dopamine in fine-tuning cone- and rod-driven vision.” G Protein Signaling Mechanisms in the Retina, 2014, pp. 121–41. Scopus, doi:10.1007/978-1-4939-1218-6_8. Full Text

Calvert, P. D., and V. Y. Arshavsky. “Light-driven translocation of signaling proteins in vertebrate photoreceptors.” Encyclopedia of the Eye, 2010, pp. 577–80. Scopus, doi:10.1016/B978-0-12-374203-2.00176-7. Full Text

Martemyanov, Kirill A., and Vadim Y. Arshavsky. Biology and functions of the RGS9 isoforms. Vol. 86, 2009, pp. 205–27. Pubmed, doi:10.1016/S1877-1173(09)86007-9. Full Text

Hanke-Gogokhia, Christin, et al. “Apical CLC-2 in retinal pigment epithelium is crucial for survival of the outer retina.Faseb J, vol. 35, no. 7, July 2021, p. e21689. Pubmed, doi:10.1096/fj.202100349R. Full Text

Khelashvili, George, et al. “Unusual mode of dimerization of retinitis pigmentosa-associated F220C rhodopsin.Sci Rep, vol. 11, no. 1, May 2021, p. 10536. Pubmed, doi:10.1038/s41598-021-90039-3. Full Text

Skiba, Nikolai P., et al. “TMEM67, TMEM237, and Embigin in Complex With Monocarboxylate Transporter MCT1 Are Unique Components of the Photoreceptor Outer Segment Plasma Membrane.Mol Cell Proteomics, vol. 20, Apr. 2021, p. 100088. Pubmed, doi:10.1016/j.mcpro.2021.100088. Full Text

Lewis, Tylor R., et al. “Photoreceptor Disc Enclosure Is Tightly Controlled by Peripherin-2 Oligomerization.J Neurosci, vol. 41, no. 16, Apr. 2021, pp. 3588–96. Pubmed, doi:10.1523/JNEUROSCI.0041-21.2021. Full Text

Pearring, Jillian N., et al. “The GARP Domain of the Rod CNG Channel's β1-Subunit Contains Distinct Sites for Outer Segment Targeting and Connecting to the Photoreceptor Disk Rim.J Neurosci, vol. 41, no. 14, Apr. 2021, pp. 3094–104. Pubmed, doi:10.1523/JNEUROSCI.2609-20.2021. Full Text

Maddala, Rupalatha, et al. “Absence of S100A4 in the mouse lens induces an aberrant retina-specific differentiation program and cataract.Sci Rep, vol. 11, no. 1, Jan. 2021, p. 2203. Pubmed, doi:10.1038/s41598-021-81611-y. Full Text Open Access Copy

Sharif, Ali S., et al. “Deletion of the phosphatase INPP5E in the murine retina impairs photoreceptor axoneme formation and prevents disc morphogenesis.J Biol Chem, vol. 296, Jan. 2021, p. 100529. Pubmed, doi:10.1016/j.jbc.2021.100529. Full Text

Spencer, William J., et al. “Photoreceptor Discs: Built Like Ectosomes.Trends Cell Biol, vol. 30, no. 11, Nov. 2020, pp. 904–15. Pubmed, doi:10.1016/j.tcb.2020.08.005. Full Text

Perfilov, Maxim M., et al. “Highly photostable fluorescent labeling of proteins in live cells using exchangeable coiled coils heterodimerization.Cell Mol Life Sci, vol. 77, no. 21, Nov. 2020, pp. 4429–40. Pubmed, doi:10.1007/s00018-019-03426-5. Full Text

Wang, Luyu, et al. “Progressive optic atrophy in a retinal ganglion cell-specific mouse model of complex I deficiency.Sci Rep, vol. 10, no. 1, Oct. 2020, p. 16326. Pubmed, doi:10.1038/s41598-020-73353-0. Full Text

Pages

III, Gospe Sidney M., et al. “Progressive Optic Atrophy in a Retinal Ganglion Cell-Specific Mouse Model of Complex I Deficiency.” Investigative Ophthalmology & Visual Science, vol. 61, no. 7, 2020.

Ray, Thomas, et al. “CRB1 expresses multiple isoforms in multiple retinal cell types - reevaluating CRB1 retinopathies.” Investigative Ophthalmology & Visual Science, vol. 60, no. 9, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2019.

Lobanova, Katya, et al. “Reduced docosahexaenoic acid content impairs photoreceptor health without affecting visual signal transduction.” Investigative Ophthalmology & Visual Science, vol. 60, no. 9, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2019.

Arshavsky, Vadim Y. “How to build a photoreceptor disc?Investigative Ophthalmology & Visual Science, vol. 60, no. 9, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2019.

Spencer, William, et al. “PRCD supports the organized structure of the photoreceptor outer segment.” Investigative Ophthalmology & Visual Science, vol. 60, no. 9, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2019.

Pearring, Jillian Nydam, et al. “Ciliary Delivery of the CNG-gated Channel in Rod Photoreceptors.” Investigative Ophthalmology & Visual Science, vol. 60, no. 9, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2019.

Skiba, Nikolai P., et al. “Identification of protein components of the rod outer segment plasma membrane by label-free protein correlation profiling.” Investigative Ophthalmology & Visual Science, vol. 59, no. 9, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018.

Maddala, Rupalatha, et al. “Deficiency of S100A4, a Ca2+-binding protein, Induces Expression of Neuronal S100A5 and the Retinal Specific Transcriptome in mouse lens.” Investigative Ophthalmology & Visual Science, vol. 59, no. 9, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018.

Lobanova, Ekaterina, et al. “An increase in proteolytic capacity delays photoreceptor loss in retinal degeneration.” Investigative Ophthalmology & Visual Science, vol. 58, no. 8, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2017.

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