Ophthalmology & Visual Sciences, Medical School
Biological Chemistry, Medical School
Our research focuses on studies of the molecular mechanisms responsible for inherited forms of retinal degeneration causing devastating loss of vision in affected individuals. Our efforts have contributed to the identification of disease genes whose mutations result in early and severe forms of retinal degeneration. Normally these genes are expressed in the retina and retinal pigment epithelium, and encode proteins necessary for the function and survival of the light absorbing rod and cone photoreceptor cells. Disease-associated mutations disrupt cellular processes including the metabolism of vitamin A needed to produce the light-absorbing chromophore 11-cis retinal, the phagocytic uptake of membrane debris from the subretinal space, and the structure and lipid composition of the photoreceptor cells. Our ongoing research focuses on analysis of the normal function and pathogenic mechanisms associated with these genetic defects, in studies involving biochemical assays of protein function and enzyme activity in vitro, and phenotypic characterization of mouse and rat models corresponding to human forms of disease. We are using this information to develop novel strategies for therapeutic intervention that we are testing in preclinical trials.
1995 Career Development Fund for Women Faculty Award, University of Michigan
1995 Rackham Partnership Program Award, Sponsor, University of Michigan
1999 Research to Prevent Blindness Lew R. Wasserman Merit Award
2005 Elizabeth Caroline Crosby Research Award, NSF ADVANCE Project
2008 Senior Scientific Investigator Award, Research to Prevent Blindness
2009 Research to Prevent Blindness Senior Scientific Investigator Award
2010 Fellow, Association for Research in Vision and Ophthalmology
2014 BrightFocus Foundation, Elizabeth Anderson Award for Macular Degeneration Research
Janecke, AR, Thompson, DA, Utermann, G, Becker, C, Hübner, CA, Schmid, E, McHenry, CL, Nair, AR, Rüschendorf, F, Heckenlively, JR, Wissinger, B, Nürnberg, P, and Gal, A. Mutations in RDH12 encoding a photoreceptor cell retinol dehydrogenase cause childhood-onset retinal dystrophy. Nat Genet. 2004 Aug;36(8):850-4.
Kurth, I, Thompson, DA, Rüther, K, Feathers, KL, Chrispell, JD, Schroth, J, McHenry, CL, Schweizer, M, Gal, A, and Hübner, C. Targeted disruption of the murine retinal dehydrogenase gene Rdh12 does not limit visual cycle function. Mol Cell Biol. 2007 Feb;27(4):1370-9.
Chrispell, JD, Feathers, KL, Kane, M, Brooks M, Khanna R, Kurth I, Huebner C, Gal A, Mears A, Swaroop, A, Napoli JL, Sparrow, JR, and Thompson, DA. RDH12 activity and effects on retinoid processing in the murine retina. J Biol Chem. 2009 Aug 7;284(32):21468-77.
Chen, C, Thompson, DA, and Koutalos, Y. Reduction of all-trans retinal in vertebrate rod photoreceptors requires the combined action of RDH8 and RDH12. 2012 Jul 13;287(29):24662-70.
Shelby SJ, Colwill K, Dhe-Paganon S, Pawson T, Thompson DA. MERTK Interactions with SH2-Domain Proteins in the Retinal Pigment Epithelium. PLoS One. 2013;8(2):e53964.
Yao J, Jia L, Shelby SJ, Ganios AM, Feathers K, Thompson DA, Zacks DN. Circadian and noncircadian modulation of autophagy in photoreceptors and retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2014 Apr 29;55(5):3237-46.
Yao J, Jia L, Khan N, Lin C, Mitter SK, Boulton ME, Dunaief JL, Klionsky DJ, Guan JL, Thompson DA, Zacks DN. Deletion of autophagy inducer RB1CC1 results in degeneration of the retinal pigment epithelium. Autophagy. 2015;11(6):939-53.
Shelby SJ, Feathers KL, Ganios AM, Jia L, Miller JM, Thompson DA. MERTK signaling in the retinal pigment epithelium regulates the tyrosine phosphorylation of GDP dissociation inhibitor alpha from the GDI/CHM family of RAB GTPase effectors. Exp Eye Res. 2015 Nov;140:28-40.
Chen C, Adler L 4th, Goletz P, Gonzalez-Fernandez F, Thompson DA, Koutalos Y. Interphotoreceptor retinoid-binding protein removes all-trans-retinol and retinal from rod outer segments, preventing lipofuscin precursor formation. J Biol Chem. 2017 Nov 24;292(47):19356-19365.
Thompson DA, Ali RR, Banin E, Branham KE, Flannery JG, Gamm DM, Hauswirth WW, Heckenlively JR, Iannaccone A, Jayasundera KT, Khan NW, Molday RS, Pennesi ME, Reh TA, Weleber RG, Zacks DN; Monaciano Consortium. Advancing therapeutic strategies for inherited retinal degeneration: recommendations from the Monaciano Symposium. Invest Ophthalmol Vis Sci. 2015 Feb 9;56(2):918-31.
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