Biomedical Research Education & Training
Faculty Member

Shieh, Bih-Hwa, Ph.D.
Associate Professor of Pharmacology

Lab Url: N/A

Phone Number: (615) 343-0441

Email Address: bih-hwa.shieh@vanderbilt.edu

Shieh, Bih-Hwa's picture
Academic history
B.S., National Taiwan University
M.S., Pharmacological Institute, National Taiwan University, Taipei, Taiwan, ROC
Ph.D., State University of New York at Stony Brook, NY
Postdoc, UC San Diego

Office Address   Mailing Address

402 Robinson Res Bldg (MRB1)

402 Robinson Res Bldg (MRB1) 6600


Research Keywords
PDZ domains, Scaffolding proteins, vision, TRP, PKC, Phospholipase C, Phototransduction, Drosophila, CaMKII,Biochemistry,Drosophila,Genetics,Genomics,Ion transport,Kinase,Mass spectroscopy,Membrane,Mutation,Neuroscience,Phosphorylation,Protein Structure,Proteomics,Signal transduction,Vision

Research Specialty
Regulation of visual transduction by a novel macromolecular complex containing PKC, PLC-beta and the TRP calcium channels

Research Description
My research focuses on the molecular basis of the visual transduction using the fruitfly, Drosophila melanogaster, as a model system. Visual signaling is the process that converts the signal of light into a change of membrane potential in photoreceptors. In Drosophila, visual transduction is a Gq-coupled PLCβ-mediated process leading to the opening of TRP and TRPL cation channels. This mechanism appears utilized in the photosensitive retinal ganglion cells, which synapse with suprachiasmatic nucleus in the hypothalamus for photoentrainment critical for resetting of the circadian clock in mammals. In Drosophila, following the opening of TRP and TRPL the increase of cytoplasmic Ca2+ activates eye-PKC, a conventional PKC critical for negative regulation of the visual signaling. Mutant flies missing eye-PKC displays deficits including slow deactivation, and abnormal light adaptation. Significantly, eye-PKC is assembled into a multi-molecular protein complex by interacting with INAD, a scaffolding protein, which also simultaneously tethers TRP and PLCβ. The formation of this signaling complex is critical for fast kinetics of the visual response. The overall objective of my research is to elucidate how this macromolecular protein complex promotes the fast kinetics of the visual signaling. We will employ a multi-disciplinary approach including biochemical, cell biological, molecular biological, and electrophysiological analyses for better insights into the G-protein coupled PLCβ-mediated pathway.


Publications
Lu, H, Leung, HT, Wang, N, Pak, WL, Shieh, BH. Role of Ca2+/calmodulin-dependent protein kinase II in Drosophila photoreceptors. J Biol Chem, 284(17), 11100-9, 2009 PMCID:2670115

Peng, L, Popescu, DC, Wang, N, Shieh, BH. Anchoring TRP to the INAD macromolecular complex requires the last 14 residues in its carboxyl terminus. J Neurochem, 104(6), 1526-35, 2008 PMCID:2275663

Wang, N, Leung, HT, Pak, WL, Carl, YT, Wadzinski, BE, Shieh, BH. Role of protein phosphatase 2A in regulating the visual signaling in Drosophila. J Neurosci, 28(6), 1444-51, 2008 PMCID:2275662

Popescu, DC, Ham, AJ, Shieh, BH. Scaffolding protein INAD regulates deactivation of vision by promoting phosphorylation of transient receptor potential by eye protein kinase C in Drosophila. J Neurosci, 26(33), 8570-7, 2006 PMCID:1577681

Parker, L.L., Backstrom, J. R., Sanders-Bush, E., and Shieh, B.-H.. Agonist-induced phosphorylation of the serotonin 5HT2c receptor regulates its interaction with multiple PDZ protein 1. J. Biol. Chem., 278, 21576-83, 2003

Parker, LL, Backstrom, JR, Sanders-Bush, E, Shieh, BH. Agonist-induced phosphorylation of the serotonin 5-HT2C receptor regulates its interaction with multiple PDZ protein 1. J Biol Chem, 278(24), 21576-83, 2003

Shieh, B.-H., Parker, L., and Popescu, D.. Protein kinase C isoforms in Drosophila. Journal of Biochemistry, 132, 523-27, 2002

Shieh, BH, Parker, L, Popescu, D. Protein kinase C (PKC) isoforms in Drosophila. J Biochem (Tokyo), 132(4), 523-7, 2002

Kumar, R and Shieh, B.-H. The Second PDZ domain of INAD is a type I domain involved in binding to eye protein kinase C: mutational analysis and naturally occurring variants. J. Biol. Chem., 276, 24971-7, 2001

Kumar, R, Shieh, BH. The second PDZ domain of INAD is a type I domain involved in binding to eye protein kinase C. Mutational analysis and naturally occurring variants. J Biol Chem, 276(27), 24971-7, 2001

Liu, M, Parker, LL, Wadzinski, BE, Shieh, BH. Reversible phosphorylation of the signal transduction complex in Drosophila photoreceptors. J Biol Chem, 275(16), 12194-9, 2000

Liu, M., Parker, L.L. Wadzinski, B. E., and Shieh B.-H. Reversible phosphorylation of the signal transduction complex in Drosophila photoreceptors. J. Biol. Chem., 275, 12194-12199, 2000

Adamski, FM, Timms, KM, Shieh, BH. A unique isoform of phospholipase Cbeta4 highly expressed in the cerebellum and eye. Biochim Biophys Acta, 1444(1), 55-60, 1999

Adamski, FM., Timms, K.M., and Sheih, B.-H. Unique Isoform of Phospholipase C-beta4 is Preferentially Expressed in the Eye and Cerebellum of the Rat. Biochimica et Biophysica Acta., 1444, 55-60, 1999

Brash, A.R., Koljak, R., Boutaud, O., Sheih, B-H., and Samel, N. Allene oxide synthesis by a naturally fusion protein with lipoxygenase and catalase-related domains. Essential Fatty Acids and Eicosanoids, 386389, 1999

Adamski, F.M., Zhu, M.-Y, Bahiraei, F., and Shieh, B.-H. Interaction of Eye-Protein Kinase C and INAD in Drosophila: Localization of binding domains and electrophysiological characterization of a loss of association in transgenic flies. J. Biol. Chem., 273, 17713-17719, 1998

Adamski, FM, Zhu, MY, Bahiraei, F, Shieh, BH. Interaction of eye protein kinase C and INAD in Drosophila. Localization of binding domains and electrophysiological characterization of a loss of association in transgenic flies. J Biol Chem, 273(28), 17713-9, 1998

Koljak, R, Boutaud, O, Shieh, BH, Samel, N, Brash, AR. Identification of a naturally occurring peroxidase-lipoxygenase fusion protein. Science, 277(5334), 1994-6, 1997

Koljak, R., Boutaud, O., Shieh, B-H, Samel, N., and Brash, A. R. Identification of a Naturally Occurring Peroxidase-lipoxygenase Fusion Protein Science . , 277, 1994-1996, 1997

Shieh, B.-H., Zhu, M.-Y., Lee, J. K., Kelly, I. M., and Bahiraei, F. Association of INAD with NORPA is Essential for Controlled Activation and Deactivation of Phototransduction in Drosophila . Proc. Natl. Acad. Sci. USA , 94, 12682-12687 , 1997

Shieh, BH, Zhu, MY, Lee, JK, Kelly, IM, Bahiraei, F. Association of INAD with NORPA is essential for controlled activation and deactivation of Drosophila phototransduction in vivo. Proc Natl Acad Sci U S A, 94(23), 12682-7, 1997 PMCID:25084

Brash, A. R., Boeglin, W. E., Chang, M. S. and Shieh, B.-H. Purification and Molecular Cloning of an 8R- Lipoxygenase from the Coral Plexaura homomalla Reveal the Related Primary Structures of R- and S-Lipoxygenases . J. Biol. Chem. , 271, 20949-20957, 1996

Brash, AR, Boeglin, WE, Chang, MS, Shieh, BH. Purification and molecular cloning of an 8R-lipoxygenase from the coral Plexaura homomalla reveal the related primary structures of R- and S-lipoxygenases. J Biol Chem, 271(34), 20949-57, 1996

Shieh B-H and Zhu M-Y. Regulation of the TRP Ca2+ channel by INAD in Drosophila photoreceptors. Neuron, 16, 991-998, 1996

Shieh, BH, Zhu, MY. Regulation of the TRP Ca2+ channel by INAD in Drosophila photoreceptors. Neuron, 16(5), 991-8, 1996

Shieh B-H and Niemeyer B. A novel protein encoded by the INAD gene regulates recovery of the visual transduction Drosophila. Neuron, 14, 201-210, 1995

Shieh, BH, Niemeyer, B. A novel protein encoded by the InaD gene regulates recovery of visual transduction in Drosophila. Neuron, 14(1), 201-10, 1995

Ondek, B, Hardy, RW, Baker, EK, Stamnes, MA, Shieh, BH, Zuker, CS. Genetic dissection of cyclophilin function. Saturation mutagenesis of the Drosophila cyclophilin homolog ninaA. J Biol Chem, 267(23), 16460-6, 1992

Ondek, B., Hardy, R. W., Baker, E. K., Stamnes, M. A., Shieh, B.-H. and Zuker, C. S. Genetic Dissection of Cyclophilin Function: Saturation Mutagenesis of the Drosophila Homolog ninaA.. J. Biol. Chem., 267, 16460-16466., 1992

Stamnes, M. A., Shieh, B-H., Harris, G. L., Chuman, L. and Zuker, C. S. The Cyclophilin Homolog ninaA is a Tissue Specific Integral Membrane Protein Required for the Proper Synthesis of a Subset of Drosophila . Rhodopsins. Cell , 65, 219-227, 1991

Stamnes, MA, Shieh, BH, Chuman, L, Harris, GL, Zuker, CS. The cyclophilin homolog ninaA is a tissue-specific integral membrane protein required for the proper synthesis of a subset of Drosophila rhodopsins. Cell, 65(2), 219-27, 1991

Smith, D. P., Shieh, B.-H. and Zuker, C. S. Isolation and Structure of an Arrestin Gene from Drosophila. Proc. Natl. Acad. Sci., 87, 1003-1007, 1990

Smith, DP, Shieh, BH, Zuker, CS. Isolation and structure of an arrestin gene from Drosophila. Proc Natl Acad Sci U S A, 87(3), 1003-7, 1990 PMCID:53398

Shieh, B.-H., Stamnes, M. A., Seavello, S., Harris, G. L., and Zuker, C. S. The ninaA Gene Required for Visual Transduction in Drosophila Encodes a Homolog of the Cyclosporin A Binding Protein. Nature, 338 , 67-70, 1989

Shieh, BH, Stamnes, MA, Seavello, S, Harris, GL, Zuker, CS. The ninaA gene required for visual transduction in Drosophila encodes a homologue of cyclosporin A-binding protein. Nature, 338(6210), 67-70, 1989

Shieh, B.-H., Ballivet, M., and Schmidt, J. Acetylcholine Receptor Synthesis Rate and Levels of Receptor Subunits mRNAs in Chick Muscle. Neuroscience , 24, 178-188, 1988

Shieh, BH, Ballivet, M, Schmidt, J. Acetylcholine receptor synthesis rate and levels of receptor subunit messenger RNAs in chick muscle. Neuroscience, 24(1), 175-87, 1988

Shieh, B.-H., Ballivet, M. and Schmidt, J. Quantitation of an Alpha Subunit Massage Intermediate. Evidence for Transcriptional Activation in the Control of Acetylcholine Receptor Expression in Denervated Chick Skeletal Muscle.. J. Cell Biol., 104 , 1337-1341, 1987

Shieh, BH, Ballivet, M, Schmidt, J. Quantitation of an alpha subunit splicing intermediate: evidence for transcriptional activation in the control of acetylcholine receptor expression in denervated chick skeletal muscle. J Cell Biol, 104(5), 1337-41, 1987 PMCID:2114465

Chang, C. C., Su, M. J., Hong, S. J., Shieh, B.-H. and Chiou, L. C. A Comparison of Antagonisms by Neostigmine and Diaminopyridine against the Neuromuscular Block Caused by Cobrotoxin and (+)-Tubocurarine. J. Pharm. Pharmacol., 38, 153-155, 1986

Chang, CC, Su, MJ, Hong, SJ, Shieh, BH, Chiou, LC. A comparison of the antagonisms by neostigmine and diaminopyridine against the neuromuscular block caused by cobrotoxin and (+)-tubocurarine. J Pharm Pharmacol, 38(2), 153-5, 1986

Chang, CC, Su, MJ, Shieh, BH, Lin, HL, Hong, SJ. Potentiation between neostigmine and 3,4-diaminopyridine in antagonizing the neuromuscular block induced by D-tubocurarine. Proc Natl Sci Counc Repub China B, 8(3), 235-9, 1984

Schneider, M, Shieh, BH, Pezzementi, L, Schmidt, J. Trifluoperazine stimulates acetylcholine receptor synthesis in cultured chick myotubes. J Neurochem, 42(5), 1395-401, 1984

Schneider, M., Shieh, B.-H., Pezzementi, L. and Schmidt, J. Trifluoperazine Stimulates Acetylcholine Receptor Synthesis in Cultured Chick Myotubes.. J. Neurochemistry, , 42, 1395-1401, 1984

Shieh, B.-H., Pezzementi, L. and Schmidt, J. Extracellular Potassium and the Regulation of Acetylcholine Receptor Synthesis in Embryonic Chick Muscle Cells. Brain Research, 263, 259-265, 1983

Shieh, BH, Pezzementi, L, Schmidt, J. Extracellular potassium and the regulation of acetylcholine receptor synthesis in embryonic chick muscle cells. Brain Res, 263(2), 259-65, 1983


Postdoctoral Position Available
No

Postdoctoral Position Details
N/A

Updated Date
06/03/2009