Vision is the most important of our senses. It enables us to richly experience and interact with the world around us. Inherited diseases of the visual system that lead to partial or total blindness severely diminish the quality of life and present a serious social and economic burden.
Research in my laboratory is directed toward identifying and characterizing vertebrate retinal photoreceptor proteins and elucidating their role in 1) phototransduction and related signal transduction pathways; 2) photoreceptor cell structure and morphogenesis; 3) retinal cell-cell and cell-extracellular matrix interactions; and 4) various inherited retinal degenerative diseases including retinitis pigmentosa and macular degeneration that are the leading causes of blindness in the developed world. We are also developing and applying new technology to the study of membrane proteins and treatments for retinal degenerative diseases. To accomplish these goals, we are utilizing a variety of current and emerging biochemical, biophysical, immunochemical, molecular and cell biology approaches to 1) purify and reconstitute membrane proteins into lipid vesicles for structure-function analyses; 2) identify and characterize important structural, functional, and regulatory protein domains; 3) define specific protein-protein interactions responsible for the formation of macromolecular assemblies; 4) develop novel reagents and cell and animal models for analysis of retinal degenerative diseases; and 5) evaluate diagnostic and therapeutic interventions for selective retinal degenerative diseases.
Some of the techniques currently being employed in my laboratory include:
The experimental systems we work on and current research areas of interest are briefly described on this page.
Wu, WW and Molday RS. (2003). Defective discoidin domain structure, subunit assembly, and endoplasmic reticulum processing of retinoschisin are primary mechanisms responsible for X-linked retinoschisis. J Biol Chem 278:28139-46.
Loewen, CJ, Moritz OL, Tam BM, Papermaster DS, and Molday RS. (2003). The role of subunit assembly in peripherin-2 targeting to rod photoreceptor disk membranes and retinitis pigmentosa Mol Biol Cell. 14:3400-13.
Ahn J., Beharry, S., Molday, L.L. and Molday, R.S. (2003). Functional interaction between the two halves of the photoreceptor-specific ATP binding cassette protein ABCR (ABCA4). Evidence for a non-exchangeable ADP in the first nucleotide binding domain. J. Biol. Chem., 278:39600-39608.
Weber, B.H.F., Schrewe, H., Molday, L.L., Gehrig, A., White, K., Seeliger, M.W, Jaissle, G.B., Friedburg, C., Tamm, T., and Molday, R.S. (2002) Inactivation of the murine X-linked juvenile retinoschisis gene, Rs1h, suggests a role of retinoschisin in retinal cell layer organization and synaptic structure. Proc. Natl. Acad. Sci. U.S.A. 99:6222-6227.
Zhong, H., Molday, L.L., Molday, R.S. and Yau, K-W. (2002) The Heteromeric Cyclic Nucleotide-gated Channel Adopts a 3A:1B stoichiometry. Nature 420:193-198.
Warren, R. and Molday RS. (2002) Regulation of the rod photoreceptor cyclic nucleotide-gated channel. Adv Exp Med Biol. 514:205-23.
Poetsch, A., Molday, L.L. and Molday, R.S. (2001) The cGMP-gated Channel and Related Glutamic Acid Rich Proteins Interact with Peripherin-2 at the Rim Region of Rod Photoreceptor Disc Membranes. J. Biol. Chem. 276:48009-48016.
Bungert, S., Molday, L.L. and Molday, R.S. (2001) Membrane Topology of ABCR (ABCA4), ABC1 (ABCA1), and Related ABCA Transporters. J. Biol. Chem. 276:23539-23546
Loewen, C.J.R. and Molday, R.S. (2001) Molecular Characterization of Peripherin-2 and Rom-1 Mutants Responsible for Digneic Retinitis Pigmentosa. J. Biol. Chem. 276:22388-22396.
Molday, L.L., Sauer, C.G., Weber, B.H.F., and Molday, R.S. (2001) Molecular Characterization and Localization of RS1, the Protein Encoded by the Gene for X-linked Juvenile Retinoschisis. Invest. Ophthalmol. Vis. Sci. 42:816-825.
Molday, L.L., Rabin, A.R., and Molday, R.S. (2000) ABCR Expression in Foveal Cone photoreceptors and Its Role in Stargardt Macular Dystrophy. Nature Genetics 25:257-258.