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Theodore Wensel Baylor College of Medicine Department: Biochemistry and Molecular Biology Address: One Baylor Plaza, Rm. N430.01 Houston, TX 77030 Phone: 713-798-6994 Fax: 713-796-9438 Email: twensel@bcm.tmc.edu Web: ncmi.bcm.tmc.edu/~twensel/

Education

B.S., Chemistry, U. S. Fla. (1980)
Ph.D. Chemistry, U.C. Davis (1984)
Stanford, Cell Biology (1984-1988)

Honors

Welch Chair of Biochemistry, 2003
Barbara and Corbin J. Robertson Jr. Presidential Award for Excellence in Education 2005

Research Topic

Structure and Dynamics of Signal Transducing Membranes

Research Description

STRUCTURAL DYNAMICS OF SIGNAL TRANSDUCING MEMBRANES
We use a multidisciplinary approach to understand the molecular mechanisms of G protein-mediated signal transduction in neurons of the retina and brain. New molecules and their functional roles are discovered, mechanisms of known molecules are explored at all levels from the atomic to the cellular, to intact animals. Techniques used include fluorescence spectroscopy and photobleaching recovery, electron and fluorescence microscopy, x-ray crystallography, genetics and reverse genetics, bioinformatics, biochemistry and molecular biology, and computational modeling of signaling pathways.

Selected Publications

• Zhang, X., Wensel, T. G., and Yuan, C. (2006). Tokay Gecko Photoreceptors Achieve Rod-like Physiology with Cone-like Proteins. Photochem Photobiol.82:1452.
  Gross, A. K., Decker, G., Chan, F., Sandoval, I. M., Wilson, J. H., Wensel, T. G. (2006) Defective development of photoreceptor membranes in a mouse model of recessive retinal degeneration. Vision Res. 46:4510-4518.
  Krispel, C. M. Chen, D., Chen, Y-J. Martemyanov, K. A., Quillinan, N., Arshavsky, V. Y., Wensel, T. G. Chen, C-K. Burns, M. E. (2006) RGS expression sets the duration of signaling in rod photoreceptors. Neuron 51:409-16.
  Meltzer, R. H., Lurtz, M. M., Wensel, T. G., Pedersen, S.E. (2006) Nicotinic Acetylcholine Receptor Channel Electrostatics Determined by Diffusion Enhanced Luminescence Energy Transfer. Biophys. J. 91:1315-1324.
  Meltzer, R. H., Thompson, E., Soman, K., Song, X.-Z., Wensel, T. G.Briggs, J. M., Pedersen, S.E. (2006) Electrostatic Steering at Acetylcholine Binding Sites. Biophys. J. 91:1302-1314.
  Iyer, M. N., He, F., Wensel, T. G., Mieler, W. F., Benz, M. S., Holz, E. R. (2006) Clearance of intravitreal moxifloxacin. Invest. Ophthalmol. Vis. Sci. 47:317-319.
  Wensel, T. G., Gross, A. K., Chan, F., Sykoudis, K., Wilson, J. H. (2005) Rhodopsin-EGFP knock-ins for imaging quantal gene alterations. Vis. Res. 45:3445-3453.
  Wiszniewski, W., Zaremba, C. M., Yatsenko, A. M., Jamrich, M., Wensel, T., Lupski, J. R., Lewis, R. A. (2005) ABCA4 mutations causing mislocalization are found frequently in patients with severe retinal dystrophies. Hum. Mol. Genet. 14:2769-2778 COVER
  Wensel, T.G., He, F., Malinski, J.A. 2005. Purification, reconstitution on lipid vesicles, and assays of PDE6 and its activator G protein, transducin. Methods Mol. Biol. 307:289-314.
  Hu, G., Wensel, T. G. 2004. Characterization of R9AP, a membrane anchor for the photoreceptor GAP, RGS9-1. Methods Enzymol. 390:178-196.
  Zhang, Z., Melia, T. J., He, F., Yuan, C., McGough, A., Schmid, M. F., Wensel, T.G., 2004. How a G-protein binds a membrane. J. Biol. Chem. 279:33937-33945
  Chan, F., Bradley, A., Wensel, T.G., Wilson, J.H. 2004. Knock-in human rhodopsin-GFP fusions as mouse models for human disease and targets for gene therapy . Proc. Natl. Acad. Sci. USA 101:9109-9114
  He, F., Mao, M., Wensel, T.G. 2004. Enhancement of phototransduction G protein-effector interactions by phosphoinositides J. Biol. Chem. 279:8986-90.
  Madabushi, S., Gross, A. K., Philippi, A., Meng, E. C., Wensel, T. G., Lichtarge, O. 2004. Evolutionary trace of G protein-coupled receptors reveals clusters of residues that determine global and class-specific functions. J. Biol. Chem. 279:8126-32.
  Wilson, J.H., Wensel, T.G. 2003. The nature of dominant mutations of rhodopsin and implications for gene therapy. Mol. Neurobiol. 28:149–158.
  Zhang, L., El-Hodiri, H. M., Ma, H. -F. Zhang, X., Servetnick, M., Wensel, T. G., and Milan Jamrich, M. 2003. Targeted expression of the dominant negative FGFR-4a in the eye using Xrx1A regulatory sequences interferes with normal retinal development. Development, 130:4177-4186.
  Burns, M.E. and Wensel, T.G. (2003). From molecules to behavior: new clues for RGS function in the striatum. Neuron 38: 853–856.

• Chen, C.-K., Eversole-Cire, P., Zhang, H., Macino, V., Chen, Y.-J., He, W., Wensel, T.G. and Simon, M. I. (2003). Instability of GGL domain-containing RGS proteins in mice lacking the G-protein beta subunit Gbeta5. Proc. Natl. Acad. Sci. USA 100: 6604-6609.
• Imanishi, Y., Li, N., Sokal, I., Sowa, M.E., Lichtarge, O., Wensel, T.G., Saperstein, D.A., Baehr, W., Palczewski, K. (2002). Characterization of Retinal Guanylate cyclase-Activating protein 3 (GCAP3) From Zebrafish to man. Eur. J. Neurosci. 65.15: 63-78.
• Sierra, D.A., Gilbert, D.J., Householder, D. Grishin, N.V., Yu, K., Ukidwe, P., Barker, S., He, W., Wensel, T.G., Otero, G., Brown, G., Copeland, N.G., Jenkins, N.A., Wilkie, T.M. (2002). Evolution of The Regulators of G Protein Signaling (RGS) Multigene Family in Mouse and Human. Genomics 79: 177-185.
• Hu, G. and Wensel, T.G. (2002). R9AP, an anchor protein for the photoreceptor GAP RGS9-1. Proc. Natl. Acad. Sci. USA 99: 9755-9760.
• He, W. and Wensel, T.G. (2002). Approaches to RGS function in visual signal transduction. Methods Enzymol. 344:725-740.
• Hu, G., Jang, G.-F., Cowan, C.W., Wensel, T.G., Palczewski, K. (2001). Phosphorylation of RGS9-1 by an endogenous protein kinase in bovine rod outer segments. J. Biol. Chem. 276: 22287-22295.
• Cowan, C.W., He, W. and Wensel, T.G. (2001). RGS Proteins: Lessons from the RGS9 subfamily. Progress in Nucleic Acid Research and Molecular Biology 65: 341-359.
• He., W., Cowan, C.W., Melia, T.J., Jr., Wensel, T.G. (2001). Dependence of RGS9-1 membrane attahment on its C-terminal tail. J. Biol. Chem. 276: 48961-48966.
• Slep, K.C., Kercher, M A., He, W., Cowan, C.W., Wensel, T.G. and Sigler, P.B. (2001). Structural determinants for regulation of phosphodiesterase by a G-protein at 2.0 Å. Nature 409: 1071-1077.
• Sowa, M.E., He, W., Slep, K.C., Kercher, M.A., Lichtarge, O. and Wensel, T.G. (2001). Prediction and Confirmation of a Site Critical for Effector Regulation of RGS Domain Activity. Nat. Struct. Biol. 8: 234-237. (COVER)
• Lyubarsky, A.L., Chen, C.-K., Naarendorp, F., Zhang, X., Wensel, T., Simon, M.I., Pugh, E.N., Jr. (2001). RGS9-1 is required for normal inactivation of mouse cone phototransduction. Mol. Vis. 7: 71-78.
• Shroyer, N.F., Lewis, R.A., Yatsenko, A., Wensel, T.G., Lupski, J.R. (2001). Cosegregation and functional analysis of mutant ABCR (ABCA4) alleles in families that manifest both Stargardt disease and age-related macular degeneration. Human Mol. Genet. 10: 2671-2678.
• Sowa, M.E., He, W., Slep, K.C., Kercher, M.A., Lichtarge, O. and Wensel, T.G. (2001). Prediction and confirmation of a site critical for effector regulation of RGS domain activity. Nat. Struct. Biol. 8: 234-237 (cover).
• Sowa, M.E., He, W., Wensel, T.G. and Lichtarge, O. (2000). A regulator of G protein signaling interaction surface linked to effector specificity. Proc. Natl. Acad. Sci. USA 97: 1483-1488.
• Womack, K.B., Gordon, S.E., He, F., Wensel, T.G., Lu, C.-C., Hilgemann and D.W. (2000). Do phosphatidylinositides modulate vertebrate photoransduction? J. Neurosci. 20: 2792-2799.
• Cowan, C.W., Wensel, T.G., Arshavsky, V.Y. (2000). Enzymology of GTPase acceleration in vision. Methods Enzymol., K. Palczewski, ed. 315: 524-538.
• He, F., Seryshev, A., Cowan, C.W., Wensel, T.G. (2000). Multiple zinc binding sites in retinal rod cGMP phosphodiesterase, PDE6alpha beta. J. Biol. Chem. 275: 20572-20577.
• Intody, Z., Perkins, B.D., Wilson, J.H., Wensel, T.G. (2000). Blocking transcription of the Human Rhodopsin Gene by Triplex-Mediated DNA Photocrosslinking. Nucleic Acids Res. 28: 4283-4290.
• Chen, C.-K., Burns, M.E., He, W., Wensel, T.G., Baylor, D.A. and Simon, M.I. (2000). Slowed recovery of rod photoresponse in mice lacking the GTPase accelerating protein RGS9-1. Nature. 403: 557-560.
• He, W., Lu, L, Zhang, X., El-Hodiri, H.M., Chen, C.-K., Slep, K.C., Simon, M.I., Jamrich, M. and Wensel, T.G. (2000). Modules in the photoreceptor RGS9-1/Gb5L GAP complex control effector coupling, GTPase acceleration, protein folding, and stability. J. Biol. Chem. 275: 37093-37100.
• Melia, T.J., Jr., Malinski, J.A., He, F. and Wensel, T.G. (2000). Enhancement of phototransduction protein interactions by membrane surfaces. J. Biol. Chem. 275: 3535-3542.
• Kovoor, A., Chen, C.-K., He, W., Wensel, T.G., Simon, M.I. and Lester, H.A. (2000). Co-expression of Gb5 enhances the function of two Gg subunit-like domain-containing regulators of G protein signaling proteins. J. Biol. Chem. 275: 3397-3402.
• Rahman, Z., Gold, S.J., Potenza, M.N., Cowan, C.W., Ni, Y.G., He, W., Wensel, T.G., Nestler, E.J. (1999). Cloning and characterization of RGS9-2: a striatal-enriched alternatively spliced product of the RGS9 gene. J. Neurosci. 19: 2016-2026.
• Perkins, B.D., Wensel, T.G., Vasquez, K.M., Wilson, J.H. (1999). Psoralen Photo-Crosslinking by Triplex-Forming Oligonucleotides at Multiple Sites in the Human Rhodopsin Gene. Biochemistry 38: 12850-12859.
• Melia, T.J., Sowa, M.E., Schutze, L., Wensel, T. G. (1999). Formation of helical protein assemblies of IgG and transducin on varied lipid tubules. J. Struct. Biol. 128: 119-130.
• Wensel, T.G. (1999). Heterotrimeric G Proteins: Structure, regulation, and signaling mechanisms. Chapter 2 In: Introductory Signal Transduction. Ed., A. Sitaramayya. Birkhauser, Boston, pp. 29-46.
• Zhang, K., Howes, K., He, W., Pettenati, M., Palczewski, K., Wensel, T.G., Baehr, W. (1999). Structure, alternative splicing, and expression of human photoreceptor GTPase regulatory protein (RGS9) variants. Gene 240: 23-34.
• DeMar, J.C., Rundle, D.R., Wensel, T.G., Anderson, R.E. (1999). Heterogeneous N-terminal acylation of retinal proteins. Progress in Lipid Research 38: 49-90.
• He, W., Cowan, C. W., Wensel, T. G. (1998). RGS9, a GTPase accelerator for phototransduction. Neuron 20: 95-102.
• Perkins, B.D., Wilson, J.H., Wensel, T.G., Vasquez, K.M. (1998). Triplex targets in the human rhodopsin gene. Biochemistry. 37: 11315-11322.
• Iyer, M. N., He, F., Wensel, T. G., Mieler, W. F., Benz, M. S., Holz, E. R. (2006) Clearance of intravitreal moxifloxacin. Invest. Ophthalmol. Vis. Sci. 47:317-319.
• Cowan, C.W., Fariss, R.N., Palczewski, K. and Wensel, T.G. (1998). High expression levels in cones of RGS9, the predominant GTPase accelerating protein of rods. Proc. Natl. Acad. Sci. USA 95: 5351-5356.

Lab Members

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Last edited on: August 20, 2009