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Debra A. Thompson, Ph.D.

Professor, Biological Chemistry

B.S., Western Michigan University
Ph.D., Michigan State University
Postdoctoral, Massachusetts Institute of Technology

Research Profile

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.

Awards

1995 Career Development Fund for Women Faculty Award, University of Michigan
1995 Rackham Partnership Program Award, Sponsor, University of Michigan
1999 Lew R. Wasserman Merit Award, Research to Prevent Blindness
2005 Elizabeth Caroline Crosby Research Award, NSF ADVANCE Project
2008 Senior Scientific Investigator Award, Research to Prevent Blindness

Selected Publications

Gu, S.-m., Thompson, D.A., Srikumari, C.R.S., Lorenz, B., Finckh, U., Nicoletti, A., Murthy, K.R., Rathman, M., Kumaramakckavel, G., Denton, M.J., and Gal, A. Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy. Nature Genet. 17: 194-197, 1997. http://www.nature.com/ng/journal/v17/n2/abs/ng1097-194.html

Gal, A., Li, Y., Thompson, D.A., Weir, J., Orth, U., Jacobson, S.G., Apfelstedt-Sylla, E., and Vollrath, D. Mutations in MERTK, the human ortholog of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa. Nature Genet. 26:270-271, 2000. http://www.nature.com/ng/journal/v26/n3/pdf/ng1100_270.pdf

Thompson, D.A., Li, Y., McHenry, C.L., Carlson, T.J., Ding, X., Apfelstedt-Sylla, E., Sieving, P.A., and Gal, A. Mutations in the gene encoding lecithin retinol acyltransferase are associated with early-onset severe retinal dystrophy. Nature Genet. 28:123-124, 2001. http://www.nature.com/ng/journal/v28/n2/pdf/ng0601_123.pdf

Janecke, A.R., Thompson, D.A., Utermann, G., Becker, C., Hübner, C.A., Schmid, E., McHenry, C.L., Nair, A.R., Rüschendorf, F., Heckenlively, J.R, Wissinger, B., Nürnberg, P., and Gal, A. Mutations in RDH12 encoding a photoreceptor cell retinol dehydrogenase cause childhood-onset retinal dystrophy. Nature Genet. 36, 850-854, 2004. http://www.nature.com/ng/journal/v36/n8/pdf/ng1394.pdf

Hemati, N., Feathers, K.L., Chrispell, J.D., Reed, D.M., Carlson, T.J., Thompson, D.A. RPE65 surface epitopes, protein interactions, and expression in rod- and cone-dominant species. Mol. Vis. 11, 1151-65, 2005. http://www.molvis.org/molvis/v11/a133/v11a133-hemati.pdf

Friedman, J.S., Chang, B., Kannabiran, C., Chakarova, C., Singh, H.P., Jalali, S., Hawes, N.L., Branham, K., Othman, M., Filippova, E., Thompson, D.A., Webster, A.R., Andréasson, S., Jacobson, S.G., Bhattacharya, S.S., Heckenlively, J.R., Swaroop, A. Premature truncation of a novel protein, RD3, exhibiting subnuclear localization is associated with retinal degeneration. Am J Hum Genet. 79:1059-1070, 2006. http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B8JDD-4RDPT5B-8-...

Jacobson, S.G., Cideciyan A.V., Aleman T.S., Sumaroka A., Schwartz S.B., Windsor E.A.M., Roman A.J., Heon E., Stone E.M., and Thompson D.A. RDH12 and RPE65, visual cycle genes causing Leber congenital amaurosis, do not share disease mechanism and should not share therapeutic strategy. Invest. Ophthalmol. Vis. Sci. 48, 332-338, 2007. http://www.iovs.org/cgi/reprint/48/1/332

Kurth, I., Thompson, D.A.*, Rüther, K., Feathers, K.L., Chrispell, J.D., Schroth, J., McHenry, C.L., Schweizer, M., Gal, A., and Hübner, C.* (*co-corresponding authors) Targeted disruption of the murine retinal dehydrogenase gene Rdh12 does not limit visual cycle function. Mol. Cell. Biol. 27, 1370-1379, 2007. http://mcb.asm.org/cgi/reprint/27/4/1370

Feathers, K.L., Lyubarsky, A.L., Khan, N.W., Teofilo, K., Swaroop, A., Williams, D,S., Pugh, E.N. Jr., and Thompson, D.A. Nrl-knockout mice deficient in RPE65 fail to synthesize 11-cis retinal and cone outer segments. Invest. Ophthalmol. Vis. Sci. 49, 1126-1135, 2008. http://www.iovs.org/cgi/reprint/49/3/1126

Huang, X., Finerty, P. Jr., Walker, J.R., Butler-Cole, C., Vedadi, M., Schapira, M., Parker, S.A., Turk, B.E., Thompson, D.A., Dhe-Paganon, S. Structural insights into the inhibited states of the Mer receptor tyrosine kinase. J. Struct. Biol. 165, 88-96, 2009. http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WM5-4TVHSN5-1-...

Chrispell, J.D., Feathers, K.L., Kane, M., Brooks M., Khanna R., Kurth I., Huebner C., Gal A., Mears A., Swaroop, A., Napoli J.L., Sparrow, J.R., and Thompson, D.A. RDH12 activity and effects on retinoid processing in the murine retina. J. Biol. Chem., 284, 21468-21477, 2009.
http://www.jbc.org/content/284/32/21468.full.pdf+html

Marchette, L.D., Thompson, D.A., Kravtsova, M., Ngansop, T.N., Mandal M.N.A., and Kasus-Jacobi, A. Retinol dehydrogenase 12 detoxifies 4-hydroxynonenal in photoreceptor cells. Retinol dehydrogenase 12 detoxifies 4-hydroxynonenal in photoreceptor cells. Free Radic Biol Med. 48. 16-25, 2010. http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T38-4X0PC09-2-...

Thompson, D.A.*, Khan, N.W.*, Othman, M.I.*, Chang, B., Jia, L., Heckenlively, J.R., and Swaroop, A. Rd9 Is a Naturally Occurring Mouse Model of a Common Form of Retinitis Pigmentosa Caused by Mutations in RPGR-ORF15. PLoS OneE 2012;7(5):e35865. doi: 10.1371/journal.pone.0035865.

Chen, C., Thompson, D.A., and Koutalos, Y. Reduction of all-trans retinal in vertebrate rod photoreceptors requires the combined action of RDH8 and RDH12. J Biol Chem. 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 OneE 2013;8(2):e53964. doi: 10.1371/journal.pone.0053964.

dathom@umich.edu

Office: 7313 Brehm, Kellogg Eye Center
PH: (734) 936-9504

PubMed: thompson da