Bih-Hwa Shieh, Ph.D.

Associate Professor

bih-hwa.shieh@vanderbilt.edu

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Faculty Appointments
Associate Professor of Pharmacology
Education
Ph.D., Pharmocology, Stony Brook University, Stony Brook, New YorkM.S., Pharmacology, National Taiwan University, TaipeiB.S., Pharmacy, National Taiwan University, Taipei
Office Address
402 Robinson Res Bldg (MRB1)
Nashville, TN 6600
Research Description
My research focuses on retinal degeneration. Retinal degeneration is characterized by the progressive loss of photoreceptors in the eye leading to blindness or a loss of vision. Specifically, we are interested in exploring the causes in an attempt to find ways to prevent this debilitating disease.

We use Drosophila as our experimental model organism for insights into mechanisms of degeneration. Inherited retinal degeneration in Drosophila has been explored for understanding similar processes in humans. In Drosophila, we employ a multi-disciplinary approach by combining molecular biological, cell biological, biochemical and genetics strategies to uncover the molecular basis underlying the degeneration process.

Currently, we are investigating the contribution of arrestin 1 and arrestin 2 in retinal degeneration. Both arrestins belong to the evolutionarily conserved family that plays a critical role to modulate the function of rhodopsin. In particular, we are exploring whether reversible phosphorylation of arrestins and rhodopsin affects the internalization of rhodopsin, which may orchestrate retinal degeneration.


Research Keywords
Molecular mechanism of retinal degeneration: role of rhodopsin and arrestin
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 [print-electronic]. 2009 Apr 4/24/2009; 284(17): 11100-9. PMID: 19254957, PMCID: PMC2670115, PII: M806956200, DOI: 10.1074/jbc.M806956200, ISSN: 0021-9258.

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 [print-electronic]. 2008 Mar; 104(6): 1526-35. PMID: 18036153, PMCID: PMC2275663, PII: JNC5096, DOI: 10.1111/j.1471-4159.2007.05096.x, ISSN: 1471-4159.

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. 2008 Feb 2/6/2008; 28(6): 1444-51. PMID: 18256265, PMCID: PMC2275662, PII: 28/6/1444, DOI: 10.1523/JNEUROSCI.5134-07.2008, ISSN: 1529-2401.

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. 2006 Aug 8/16/2006; 26(33): 8570-7. PMID: 16914683, PMCID: PMC1577681, PII: 26/33/8570, DOI: 10.1523/JNEUROSCI.1478-06.2006, ISSN: 1529-2401.

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 [print-electronic]. 2003 Jun 6/13/2003; 278(24): 21576-83. PMID: 12682077, PII: M210973200, DOI: 10.1074/jbc.M210973200, ISSN: 0021-9258.

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. 2003; 278: 21576-83.

Shieh BH, Parker L, Popescu D. Protein kinase C (PKC) isoforms in Drosophila. J. Biochem. 2002 Oct; 132(4): 523-7. PMID: 12359065, ISSN: 0021-924X.

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

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 [print-electronic]. 2001 Jul 7/6/2001; 276(27): 24971-7. PMID: 11342563, PII: M103570200, DOI: 10.1074/jbc.M103570200, ISSN: 0021-9258.

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. 2001; 276: 24971-7.

Liu M, Parker LL, Wadzinski BE, Shieh BH. Reversible phosphorylation of the signal transduction complex in Drosophila photoreceptors. J. Biol. Chem. 2000 Apr 4/21/2000; 275(16): 12194-9. PMID: 10766855, ISSN: 0021-9258.

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. 2000; 275: 12194-9.

Adamski FM, Timms KM, Shieh BH. A unique isoform of phospholipase Cbeta4 highly expressed in the cerebellum and eye. Biochim. Biophys. Acta. 1999 Jan 1/18/1999; 1444(1): 55-60. PMID: 9931434, PII: S0167-4781(98)00260-7, ISSN: 0006-3002.

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. 1999; 386389.

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. 1999; 1444: 55-60.

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. 1998 Jul 7/10/1998; 273(28): 17713-9. PMID: 9651370, ISSN: 0021-9258.

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. 1998; 273: 17713-9.

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. 1997 Nov 11/11/1997; 94(23): 12682-7. PMID: 9356510, PMCID: PMC25084, ISSN: 0027-8424.

Koljak R, Boutaud O, Shieh BH, Samel N, Brash AR. Identification of a naturally occurring peroxidase-lipoxygenase fusion protein. Science. 1997 Sep 9/26/1997; 277(5334): 1994-6. PMID: 9302294, ISSN: 0036-8075.

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. 1997; 94: 12682-7.

Koljak, R., Boutaud, O., Shieh, B-H, Samel, N., and Brash, A. R. Identification of a Naturally Occurring Peroxidase-lipoxygenase Fusion Protein Science. 1997; 277: 1994-6.

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. 1996 Aug 8/23/1996; 271(34): 20949-57. PMID: 8702854, ISSN: 0021-9258.

Shieh BH, Zhu MY. Regulation of the TRP Ca2+ channel by INAD in Drosophila photoreceptors. Neuron. 1996 May; 16(5): 991-8. PMID: 8630257, PII: S0896-6273(00)80122-1, ISSN: 0896-6273.

Shieh B-H and Zhu M-Y. Regulation of the TRP Ca2+ channel by INAD in Drosophila photoreceptors. Neuron. 1996; 16: 991-8.

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. 1996; 271: 20949-57.

Shieh BH, Niemeyer B. A novel protein encoded by the InaD gene regulates recovery of visual transduction in Drosophila. Neuron. 1995 Jan; 14(1): 201-10. PMID: 7826638, PII: 0896-6273(95)90255-4, ISSN: 0896-6273.

Shieh B-H and Niemeyer B. A novel protein encoded by the INAD gene regulates recovery of the visual transduction Drosophila. Neuron. 1995; 14: 201-10.

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. 1992 Aug 8/15/1992; 267(23): 16460-6. PMID: 1644830, ISSN: 0021-9258.

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. 1992; 267: 16460.

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. 1991 Apr 4/19/1991; 65(2): 219-27. PMID: 1707759, PII: 0092-8674(91)90156-S, ISSN: 0092-8674.

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. 1991; 65: 219-27.

Smith DP, Shieh BH, Zuker CS. Isolation and structure of an arrestin gene from Drosophila. Proc. Natl. Acad. Sci. U.S.A. 1990 Feb; 87(3): 1003-7. PMID: 1689056, PMCID: PMC53398, ISSN: 0027-8424.

Smith, D. P., Shieh, B.-H. and Zuker, C. S. Isolation and Structure of an Arrestin Gene from Drosophila. Proc. Natl. Acad. Sci. 1990; 87: 1003-7.

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. 1989 Mar 3/2/1989; 338(6210): 67-70. PMID: 2493138, DOI: 10.1038/338067a0, ISSN: 0028-0836.

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. 1989; 338: 67-70.

Shieh BH, Ballivet M, Schmidt J. Acetylcholine receptor synthesis rate and levels of receptor subunit messenger RNAs in chick muscle. Neuroscience. 1988 Jan; 24(1): 175-87. PMID: 3368046, PII: 0306-4522(88)90321-1, ISSN: 0306-4522.

Shieh, B.-H., Ballivet, M., and Schmidt, J. Acetylcholine Receptor Synthesis Rate and Levels of Receptor Subunits mRNAs in Chick Muscle. Neuroscience. 1988; 24: 178-88.

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. 1987 May; 104(5): 1337-41. PMID: 3032988, PMCID: PMC2114465, ISSN: 0021-9525.

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. 1987; 104: 1337-41.

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. 1986 Feb; 38(2): 153-5. PMID: 2870164, ISSN: 0022-3573.

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. 1986; 38: 153-5.

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. 1984 Jul; 8(3): 235-9. PMID: 6100937, ISSN: 0255-6596.

Schneider M, Shieh BH, Pezzementi L, Schmidt J. Trifluoperazine stimulates acetylcholine receptor synthesis in cultured chick myotubes. J. Neurochem. 1984 May; 42(5): 1395-401. PMID: 6142923, ISSN: 0022-3042.

Schneider, M., Shieh, B.-H., Pezzementi, L. and Schmidt, J. Trifluoperazine Stimulates Acetylcholine Receptor Synthesis in Cultured Chick Myotubes. J. Neurochemistry. 1984; 42: 1395-401.

Shieh BH, Pezzementi L, Schmidt J. Extracellular potassium and the regulation of acetylcholine receptor synthesis in embryonic chick muscle cells. Brain Res. 1983 Mar 3/21/1983; 263(2): 259-65. PMID: 6839174, PII: 0006-8993(83)90318-9, ISSN: 0006-8993.

Shieh, B.-H., Pezzementi, L. and Schmidt, J. Extracellular Potassium and the Regulation of Acetylcholine Receptor Synthesis in Embryonic Chick Muscle Cells. Brain Research. 1983; 263: 259-65.