WOLFGANG BAEHR
Wolfgang Baehr
email: wbaehr@hsc.utah.edu		 Professor of Ophthalmology & Visual Science
Adjunct Professor of Neurobiology and Anatomy
Adjunct Professor of Biology

The Baehr Lab
Neurobiology of Disease
Molecular Neurobiology

Ph.D. 1970, University of Heidelberg, Germany; Postdoctoral Fellow, 1971-1975, Max-Planck Institute of Biophysical Chemistry, Goettingen, Germany.

RESEARCH:

Phototransduction, the Retinoid Cycle, and Inherited Retinal Disease

Research in Dr. Baehr's laboratory focuses mainly on two areas of retina research: phototransduction in rods and cones, and the retinoid cycle in the retina pigment epithelium. Phototransduction takes place in photoreceptor outer segment, which is connected to the cell by a cilium. In phototransduction, the energy of photons is converted first into a chemical and then into an electrical signal. Mechanistically, activation of rhodopsin leads to activation of a cGMP phosphodieserase and hydrolysis of cyclic GMP, an event that closes cation channels located in the cell membrane. This is the beginning of an electrical impulse that is processed by other retinal neurons and eventually transmitted to the visual cortex. Blindness occurs when the phototransduction cascade does not work (e.g., retinitis pigmentosa, night blindness, cone dystrophies, color blindness). In the retinoid cycle, 11-cis-retinal, the chromophore of rhodopsin, is recycled in a pathway in which all-trans-retinal is oxidized to retinol, exported to the RPE and re-imported as 11-cis-retinal into photoreceptors to form a functional rhodopsin. Gene defects in the retinoid cycle also have drastic consequences, for example macular degeneration and Leber congenital amaurosis. We are particularly interested in gene defects linked to retina disease, and the elucidation of mechanisms leading to retinal degeneration. Much of the work in the lab is based on transgenic or knockout mice which mimic human retina disease or yield insight into mechanisms. The phototransduction genes under investigation are those encoding the subunits of cGMP phosphodiesterase (PDE6), photoreceptor specific Ca2+-binding proteins (GCAPs), guanylate cyclases, and molecular motor subunits involved in transport (kinesin-2). Genes of the retinoid cycle under investigation are lecithin retinol acyltransferase (LRAT), and retinol dehydrogenases (RDH).

Selected Publications (since 2002)

Maeda, A., Maeda, T., Sun, W., Zhang, H., Baehr, W., and Palczewski, K. (2007) Redundant and unique roles of retinol dehydrogenases in the mouse retina. Proceedings of the National Academy of Sciences USA, 104:19565-19570.

Zhang, H., Li, S., Doan, T., Rieke, F., Detwiler, P.B., Frederick, J.M., and Baehr, W. (2007) Deletion of PrBP/d impedes transport of GRK1 and PDE to photoreceptor outer segments. Proceedings of the National Academy of Sciences USA, 104(21):8857-8862.

Baehr, W., Karan, S., Maeda, T., Luo, D-G., Li, S., Bronson, J.D., Watt, C.B., Yau, K-W., Frederick, J.M., and Palczewski, K. (2007) The function of Guanylate Cyclase 1 (GC1) and Guanylate Cyclase 2 (GC2) in rod and cone photoreceptors. J. Biol. Chem., 282:8837-8847.

Maeda, A., Maeda, T., Imanishi, Y., Sun, W., Jastrzebska, B., Hatala, D.A., Winkens, H.J., Hofmann, K.P., Janssen, J.J., Baehr, W., Driessen, C.A., and Palczewski, K. (2006) RDH12, associated with Leber Congenital Amaurosis (LCA), protects photoreceptors from light-induced degeneration. J. Biol. Chem., 281: 37697-37704. Epub 2006 Oct 10.

Batten, M.L., Imanishi, Y., Tu, D.C., Doan, T., Zhu, L., Pang, J., Glushakova, L., Moise, A.R., Baehr, W., Van Gelder, R.N., Hauswirth, W.W., Rieke, F., and Palczewski, K. (2005) Pharmacological and rAAV gene therapy rescue of visual functions in a blind mouse model of Leber Congenital Amaurosis. PLoS Medicine, Nov 1;2(11).

Norton, A.W., Hosier, S., Terew, J.M., Li, N., Dhingra, A., Vardi, N., Baehr, W., and Cote, R.H. (2005) Role of the 17 kda prenyl binding protein as a regulatory protein for phototransduction in retinal photoreceptors. J Biol Chem., 280:1248-1256.

Nishiguchi, K. N., Sokal, I., Yang, L., Roychowdhury, N., Palczewski, K., Berson, E. L., Dryja, T. P., and Baehr, W. (2004) A novel (I143NT) mutation in Guanylate Cyclase-Activating Protein 1 (GCAP1) associated with autosomal dominant cone dystrophy. Invest. Ophthalmol. & Visual Science, 45:3863-3870.

Palczewski, K., Sokal, I., and Baehr, W. (2004) Photoreceptor guanylate cyclase-activating proteins: structure, function and diversity. Biochem. Biophys. Res. Commun., 322:1123-1130.

Zhang, H., Liu, X-H., Zhang, K., Chen, C-K., Frederick, J.M., Prestwich, G.D., and Baehr, W. (2004) Photoreceptor cGMP Phosphodiesterase d-Subunit (PDEd) Functions as a Prenyl Binding Protein. J. Biol. Chem. 279:407-13. Epub 2003 Oct 15.

Pennesi, M.E., Howes, K.A., Baehr, W., Samuel, M., and Wu, S.M. (2003) GCAP1 rescues cone photoreceptor responses in GCAP1/GCAP2 knockout mice. Proc. Nat. Acad. Sci. USA, 100:6783-6788.

Howes, K., Pennesi, M.E., Sokal, I., Church-Kopish, J., Schmidt, B., Margolis, P., Frederick, J.M., Rieke, F.M., Palczewski, K., Wu, S.M., Detwiler, P., and Baehr, W. (2002) GCAP1 rescues rod photoreceptor response in GCAP1/2 knockout mice. The EMBO Journal, 21:1545-1554.

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