2014-present: Associate Professor of Ophthalmology, and Neuroscience, Neuroscience Center of Excellence, LSU Health Sciences Center, New Orleans, LA
2008-2014: Assistant Professor of Ophthalmology, and Neuroscience, Neuroscience Center of Excellence, LSU Health Sciences Center, New Orleans, LA
2007-2008: Associate Research Professor in Ophthalmology, Jules Stein Eye Institute (JSEI), David Geffen School of Medicine at UCLA, CA
2004-2007: Assistant Research Professor in Ophthalmology, JSEI, UCLA School of Medicine, CA
2001-2004: Visiting Assistant Research Ophthalmologist, JSEI, UCLA School of Medicine, CA
2000-2001: Education and Science Instructor, Gunma University School of Medicine, Japan
2005: Goho Life Science International Foundation Award
2004: CAAS-Sponsored Second-Class Outstanding Scientist
1997-2000: Japan Science and Technology Agency Scholarship
1992-1994: Education Ministry of Japan-Sponsored Overseas Fellowship
Biochemistry and molecular biology of the visual cycle, photoreceptor survival and degeneration, inherited retinal degenerative diseases
The main function of the retinal photoreceptors in vision is converting light energy into electrical energy and neural signals. This signal transformation is initiated by the visual pigment consisting of an 11-cis-retinal chromophore and an opsin G-protein coupled receptor in response to light stimulation. The 11-cis-retinal chromophore keeps opsin protein in an inactive conformation and functions as a molecular switch for activating opsin. When a photon hits a visual pigment, its energy converts 11-cis-retinal to all-trans-retinal, inducing structural rearrangement and activation of opsin. The activated opsin then triggers phototransduction--a signaling cascade that converts light-activated opsin activity into electrical energy by closing the cGMP-gated ion channels in the photoreceptor membrane. Since the opsin that lacks 11-cis-retinal is no longer responsive to light, 11-cis-retinal must be regenerated and recombined with opsin to form the light sensitive visual pigment. In vertebrate eyes, visual cycle, a series of enzymatic reactions taking place in the photoreceptors and the retinal pigment epithelium, is the major biochemical pathway that regenerates 11-cis-retinal. Because the visual cycle is essential for maintaining vision, dysfunction in any proteins involved in the visual cycle causes vision impairment and retinal degenerative diseases such as Leber’s congenital amaurosis (LCA) and retinitis pigmentosa (RP), etc. The long-term goals of our research are: (1) to define the molecular mechanisms that regulate the visual cycle in the normal and diseased eyes, (2) to identify molecular pathways leading to retinal neurodegeneration in patients with aberrant visual cycle, and (3) to develop an effective therapeutic strategy for preventing or delaying retinal neurodegeneration caused by mutations in the visual cycle genes.
To achieve the goals, we are currently focusing on the following research projects: 1) identification and characterization of new regulators of the visual cycle, (2) analysis of the cellular and molecular mechanisms underlying photoreceptor death in gene-knockout and knock-in mouse models for retinal degenerative diseases, (3) identification of molecular mechanisms of interphotoreceptor retinoid-binding protein (IRBP) function in photoreceptor survival and function, and (4) genetic and pharmacological rescue of photoreceptors in mouse models for human LCA and RP. We use molecular biology, biochemistry, electrophysiology, and mouse genetics to accomplish these research projects.
Li S, Sato K, Gordon WC, Sendtner M, Bazan NG, and Jin M.
(2018) Ciliary neurotrophic factor (CNTF) protects retinal cone and rod photoreceptors
by suppressing excessive formation of the visual pigments.
J Biol Chem.
Li S, Samardzija M, Yang Z, Grimm C, and Jin M. (2016) Pharmacological Amelioration of Cone Survival and Vision in a Mouse Model for Leber Congenital Amaurosis, J Neurosci 36:5808-19.
- Lee M, Li S, Sato K, and Jin M. (2016) Interphotoreceptor Retinoid-Binding Protein Mitigates Cellular Oxidative Stress and Mitochondrial Dysfunction Induced by All-trans-Retinal, Invest Ophthalmol Vis Sci 57:1553-62.
Jin M, Li S, Hu J, Jin HH, Jacobson SG, and Bok D. (2016) Functional rescue of retinal degeneration-associated mutant RPE65 proteins, Adv Exp Med Biol 854:525-32.
- Li S, Hu J, Jin RJ, Aiyar A, Jacobson SG, Bok D, and Jin M. (2015) Temperature-sensitive retinoid isomerase activity of RPE65 mutants associated with Leber congenital amaurosis, J Biochem 158:115-25.
- Li S, Izumi T, Hu J, Jin HH, Siddiqui AA, Jacobson SG, Bok D, and Jin M. (2014) Rescue of enzymatic function for disease-associated RPE65 proteins containing various missense mutations in non-active sites, J Biol Chem 289:18943-56.
- Sato K, Li S, Gordon WC, He J, Liou IG, Hill JM, Travis GH, Bazan GN, and Jin M. (2013) Receptor interacting protein kinase-mediated necrosis contributes to cone and rod photoreceptor degeneration in the retina lacking interphotoreceptor retinoid-binding protein, J Neurosci 33:17458-68.
Li S,* Yang Z,* Hu J, Gordon WC, Bazan GN, Haas AL, Bok D, and Jin M. (2013) Secretory defect and cytotoxicity: the potential disease mechanisms for the retinitis pigmentosa (RP)-associated interphotoreceptor retinoid-binding protein (IRBP), J Biol Chem 288:11395-406 (*co-first author).
- Li S, Lee J, Zhou Y, Gordon WC, Hill JM, Bazan NG, Miner JH, and Jin M. (2013) Fatty acid transport protein 4 (FATP4) prevents light-induced degeneration of cone and rod photoreceptors by inhibiting RPE65 isomerase, J Neurosci 33:3178-89.
- Kawaguchi R, Yu J, Ter-Stepanian M, Zhong M, Cheng G, Yuan Q, Jin M, Travis GH, Ong D, Sun H. (2011) Receptor-mediated cellular uptake mechanism that couples to intracellular storage, ACS Chem Biol 6:1041-51.
- Guignard TJ, Jin M, Pequignot MO, Li S, Chassigneux Y, Chekroud K, Guillou L, Richard E, Hamel CP, and Brabet P (2010) FATP1 inhibits 11-cis retinol formation via interaction with the visual cycle retinoid isomerase RPE65 and lecithin:retinol acyltransferase, J Biol Chem 285:18759-68.
- Philpa AR,* Jin M,* Li S, Schindler E, Iannaccone A, Lam BL, Weleber RG, Fishman SA, Jacobson SG, Mullins R, Travis GH, and Stone EM (2009) Predicting the pathogenicity of RPE65 mutations, Hum Mutat 30:1183-88. (*co-first author).
Jin M, Li S, Nusinowitz S, Lloyd M, Hu J, Radu R, Bok D, and Travis GH. (2009) The role of interphotoreceptor retinoid-binding protein on the translocation of visual retinoid and survival of cone photoreceptors, J Neurosci29:1486-95.
- Kusakabe Y, Takimoto N, Jin M, and Tsuda M. (2009) Evolution of the retinoid cycle in vertebrates, Philos Trans R Soc Lond B Biol Sci 364:2897-910.
Jin M, Yuan Q, Li S, Travis GH. (2007) Role of LRAT on the retinoid isomerase activity and association of Rpe65 with membrane, J Biol Chem 282:20915-24.
Jin M, Ishida M, Katoh-Fukui Y, Tsuchiya R, Higashinakagawa T, and Arimatsu Y. (2006) Reduced pain sensitivity in mice lacking latexin, an inhibitor for metallocarboxypeptidases, Brain Res 1075:117-21.
- Kaschula CH, Jin M, Desmond-Smith NS, Li S, and Travis GH. (2006) Acyl CoA: retinol acyltransferase (ARAT) activity is present in bovine retinal pigment epithelium, Exp Eye Res 82:111-21.
Jin M, Li S, Moghrabi WN, Sun H, and Travis GH. (2005) RPE65 is the retinoid isomerase in bovine retinal pigment epithelium, Cell 122:449-59.
Jin M, Tanaka S, Sekino Y, Ren Y, Yamazaki H, Kawai-Hirai R, Kojima N, and Shirao T. (2002) A novel, brain-specific mouse drebrin: cDNA cloning, chromosomal mapping, genomic structure, expression, and functional characterization, Genomics 79: 686-92.
Jin M, Sawamoto K, Ito M, and Okano H. (2000) The interaction between the Drosophila secreted protein Argos and the EGF-receptor inhibits dimerization of the receptor and binding of secreted Spitz to the receptor, Mol Cell Biol 20:2098-2107.
- Uratani Y, Takiguchi-Hayashi K, Miyasaka N, Jin M, and Arimatsu Y. (2000) Latexin, a carboxypeptidase A inhibitor, is expressed in rat peritoneal mast cells and is associated with granular structures distinct from secretary granules and lysosomes, Biochem J 346:817-26.
- Sawamoto K, Winge P, Koyama S, Yamada C, Yoshikawa S, Jin M, Kikuchi A, and Okano H. (1999) The Drosophila Ral GTPase regulates developmental cell shape changes through the Jun NH-terminal kinase pathway, J Cell Biol 146:361-72.
- Miyasaka N, Hatanaka Y, Jin M, and Arimatsu Y. (1999) Genomic organization and regulatory elements of the rat latexin gene, which is expressed in a cell type-specific manner in both central and peripheral nervous systems, Mol Brain Res 69:62-72.
- Sawamoto K, Taguchi A, Yamada C, Jin M, and Okano H. (1998) Argos induces programmed cell death in the developing Drosophila eye by inhibition of the Ras pathway, Cell Death Differ 5:262-270.
Jin M, Uratani Y, and Arimatsu Y. (1997) Mapping to mouse chromosome 3 of the gene encoding latexin (Lxn) expressed in neocortical neurons in a region-specific manner, Genomics 39:419-421.
Jin M, Ido E, Kuwata T, Igarashi T, Cichutek K, Kurth R, Miura T, Enose Y, Chen J, and Hayami M. (1996) Replication and cytopathogenicity of human immunodeficiency virus type 1 (HIV-1)/simian immunodeficiency virus agm3 chimeric viruses in human and monkey cells: the 5' half of the HIV-1 genome is responsible for virus cytopathogenicity, J Gen Virol 77:2427-31.