Our research focuses on the investigation of monoamine oxidases and neurotransmitters from the level of transcriptional regulation, through the signalling pathways and ultimately to phenotype and behaviours. These studies will not only provide novel insights into the molecular mechanisms of brain functioning, but also contribute to a deeper understanding of the organic basis of mental disorders such as bipolar depression, schizophrenia, Alzheimers and Parkinsons diseases. Additionally, this information can be used for designing novel therapeutics, early markers for diseases.... Recent Publications: Shih, J.C. and Eiduson, S. Multiple forms of monoamine oxidase in the developing brain. Nature 224(5226):1309-10. (1969) Bach, A.W., Lan, N.C., Johnson, D.L., Abell, C.W., Bembenek, M.E., Kwan, S.W., Seeburg, P.H. & Shih, J.C. cDNA cloning of human liver monoamine oxidase A and B: molecular basis of differences in enzymatic properties. Proc. Natl. Acad. Sci. U S A. (13):4934-8. (1988) Shih JC, Chen K. Molecular studies of 5-HT receptors. Ann. N.Y. Acad. Sci. 600:206-11. (1990) Cases, O., Seif, I., Grimsby, J., Gaspar, P., Chen, K., Pournin, S., Muller, U., Aguet, M., Babinet, C. & Shih, J.C. Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. Science. 268(5218):1763-6. (1995) Grimsby J, Toth M, Chen K, Kumazawa T, Klaidman L, Adams JD, Karoum F, Gal J, Shih JC. Increased stress response and beta-phenylethylamine in MAOB-deficient mice. Nat. Genet. 17(2):206-10. (1997) Shih JC, Chen K, Ridd MJ. Monoamine oxidase: from genes to behavior. Annu. Rev. Neurosci. 22:197-217. (1999) Wong, W.K., Chen, K. & Shih, J.C. Decreased methylation and transcription repressor Sp3 up-regulated human monoamine oxidase (MAO) B expression during Caco-2 differentiation. J Biol Chem. 278(38):36227-35. (2003) Lu, R.B., Lin, W.W., Lee, J.F., Ko, H.C. & Shih, J.C. Neither antisocial personality disorder nor antisocial alcoholism is associated with the MAO-A gene in Han Chinese males. Alcohol Clin Exp Res. 27(6):889-93. (2003) Vitalis, T., Alvarez, C., Chen, K., Shih, J.C., Gaspar, P. & Cases, O. Developmental expression pattern of monoamine oxidases in sensory organs and neural crest derivatives. J Comp Neurol. 464(3):392-403. (2003) Yeung, L. P., Chen, K. & Shih, J.C. The circadian rhythm of 5-HT biosynthetic and degradative enzymes in immortalized mouse neuroendocrine pineal cell line--a model for studying circadian rhythm. Life Sci. 75(25):3017-26. (2004) Chen, K., Holschneider, D.P., Wu, W., Rebrin, I. & Shih, J.C. A spontaneous point mutation produces monoamine oxidase A/B knock-out mice with greatly elevated monoamines and anxiety-like behavior. J Biol Chem. 279(38):39645-52. (2004) Chen, K., Shih, J.C. Regulation of MAO-A and MAO-B gene expression. Curr Med Chem. (15):1995-2005. (2004) Lee, M., Chen, K., Shih, J.C., Hiroi, N. MAO-B knockout mice exhibit deficient habituation of locomotor activity but normal nicotine intake. Genes Brain Behav. 3(4):216-27. (2004) Maragos, W.F., Young, K.L., Altman, C.S., Pocernich, C.B., Drake, J., Butterfield, D.A., Seif, I., Holschneider, D.P., Chen, K. & Shih, J.C. Striatal damage and oxidative stress induced by the mitochondrial toxin malonate are reduced in clorgyline-treated rats and MAO-A deficient mice. Neurochem Res. 29(4):741-6. (2004) Ou, X.M., Chen, K. & Shih, J.C. Dual functions of transcription factors, transforming growth factor-beta-inducible early gene (TIEG)2 and Sp3, are mediated by CACCC element and Sp1 sites of human monoamine oxidase (MAO) B gene. J Biol Chem. 279(20):21021-8. (2004) Shih, J.C Cloning, after cloning, knock-out mice, and physiological functions of MAO A and B. Neurotoxicology. 25(1-2):21-30. Review (2004) Chen, K., Ou, X.M., Chen, G., Choi, S.H. & Shih, J.C. R1, a novel repressor of the human monoamine oxidase A. J Biol Chem. 280(12):11552-9. (2005) Yin, H.S., Chen, K., Kalpana, S. & Shih, J.C. Differential effects of chronic amphetamine and baclofen administration on cAMP levels and phosphorylation of CREB in distinct brain regions of wild type and monoamine oxidase B-deficient mice. Synapse 60(8):573-84. (2006) Ou, X.M., Chen, K. & Shih, J.C. Monoamine oxidase A and repressor R1 are involved in apoptotic signaling pathway. Proc Natl Acad Sci U S A. 103(29):10923-8. (2006) Ou, X.M., Chen, K. & Shih, J.C. Glucocorticoid and androgen activation of monoamine oxidase A is regulated differently by R1 and Sp1. J Biol Chem. 281(30):21512-25. (2006) Squires, L.N., Jakubowski, J.A., Stuart, J.N., Rubakhin, S.S., Hatcher, N.G., Kim, W.S., Chen, K., Shih, J.C., Seif, I., Sweedler, J.V. Serotonin catabolism and the formation and fate of 5-hydroxyindole thiazolidine carboxylic acid. J Biol Chem. 281(19):13463-70. (2006) Chen, K., Cases, O., Rebrin, I., Wu, W., Gallaher, T.K., Seif, I. & Shih J.C. Forebrain-specific expression of monoamine oxidase a reduces neurotransmitter levels, restores the brain structure, and rescues aggressive behavior in monoamine oxidase A-deficient mice. J Biol Chem. 282(1): 115-23. (2007) BRAIN RESEARCH LABORATORY of JEAN C. SHIH Ph.D. Molecular and Cellular Mechanisms of Brain Functions. Molecular Mechanisms and Functional Consequences of MAO-induced Behaviours and Synaptic Reorganization. Development of Neuroprotective and Regenerative Therapies to Mental Disorders.
                                            University of Southern California                                          
                 Department of Molecular Pharmacology and Toxicology
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