Jean Shih’s Career Profile
Jean Shih in the laboratory
Shih is one of the world’s leading researchers in molecular neuropharmacology and has contributed to our knowledge of the structure and regulation of monoamine oxidase (MAO) and its impact on behavior. Her work unveiled the structure, function and the regulation of MAO, thereby contributing to our present understanding of this enzyme’s role on the question of impulsive behavior.
She has created a series of MAO knockout mice which provide valuable models for studying the causes, treatment and prevention of alcohol and drug abuse, anxiety, violence, aging, diabetes, Parkinson’s and Alzheimer’s diseases.
Seminal contributions: In 1988, she and her collaborators first cloned human MAO A and B and demonstrated unequivocally that these two isoenzymes are made of two different proteins, a question that had puzzled investigators for over 20 years. These clones have been distributed worldwide and made this field of research progress exponentially. Her basic research provides fundamental new knowledge and also has significant clinical implications.
Jean C. Shih’s scientific career has spanned decades and traversed a challenging landscape of novel biological research. The landmark achievement of her visionary research has been her ability to advance the understanding of the monoamine oxidase (MAO) enzyme system across many disciplines and levels of analysis, enabling us to perceive its importance as one piece in the great neurobiological puzzle of genes and behavior. This work has led to the distinguished MERlT Award from NIH, twice.
Shih’s work has established a clear link between the MAO gene and behavior by creating and testing a series of MAO knockout mice. She and her collaborators discovered that MAO A deficient mice exhibit a high level of serotonin, dopamine, norepinephrine and aggressive behavior, reminiscent of the impulsivity and violence reported to occur in males of a Dutch family with MAO A deficiency. Her lab showed that the serotonin-2A receptor antagonists and vesicular monoamine transporter blocker are able to abolish the aggression. Further, her lab discovered a novel transcription factor repressing MAO gene expression, thereby providing a target for a new line of MAO inhibitors.
In summary, her scientific vision, vigor and dedication have made her a major contributor to the fundamental understanding of monoamine metabolism and receptor function.
Monoamine Oxidase: From Genes to Behavior, 1999
1999 MAO Genes to Behavior
PUBLICATIONS & PRINCIPAL CONTRIBUTIONS TO SCIENCE
1969 J. C. Shih and S. Eiduson. Multiple forms of monoamine oxidase in developing brain. Nature 224: 1309-1311.
1988 A. W. J. Bach, N. C. Lan, D. L. Johnston, C. W. Abell, M. E. Bembenek, S.-W. Kwan, P. H. Seeburg and J. C. Shih. cDNA cloning of human liver monoamine oxidase A and B: Molecular basis of difference in enzymatic properties. Proc. Natl. Acad. Sci. 85: 4934-4938.
1991 J. Grimsby, K. Chen, L.-J. Wang, N. C. Lan and J. C. Shih. Human monoamine oxidase A and B genes exhibit identical exon itron organization. Proc. Natl. Acad. Sci. 88: 3637-3641.
1992 Q.-S. Zhu, J. Grimsby, K. Chen and J. C. Shih. Promoter organization and activity of human monoamine oxidase (MAO) A and B genes. J. Neurosci. 129: 4439-4446.
1994 Q.-S. Zhu, K. Chen and J. C. Shih. Bidirectional promoter of the human monoamine oxidase (MAO) controlled by transcription factor Sp 1. J. Neurosci. 14: 7393-7403.
1995 O. Cases, I. Self, J. Grimsby, P. Gaspar, K. Chen, S. Poumin, U. Muller, M. Aguet, C. Babinet, J. C. Shih and E. De Maeyer. Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAO A. Science 268: 1763-1766.
1995 Q.-S. Zhu, K. Chen and J. C. Shih. Characterization of human 5-HT2A receptor promoter. J Neurosci. 15: 4885-4895.
1997 J. J. Kim, J. C. Shih, K. Chen, L. Chen, S. Bao, S. Maren, S. G. Anagnostaras, M. S. Fanselow, E. DeMaeyer, I. Seif and R. E. Thompson. Selective enhancement of emotional, but not motor, learning in monoamine oxidase A-deficient mice. Proc. Natl. Acad. Sci. 94: 5929-5933.
1997 J. Grimsby, M. Toth, K. Chen, T. Kumazawa, L. Klaidman, J. Adams, F. Karoum, J. Gal and J. C. Shih. Mice lacking MAO B show marked increases in B-phenylethylamine, stress responsiveness and resistance to MPTP toxicity. Nature Genetics 17: 1-5.
2002 W. K. Wong, X.-M. Ou, K. Chen and J. C. Shih. Activation of Human Monoamine Oxidase B Gene Expression by a Protein Kinase C, MAPK Signal Transduction Pathway Involves c-Jun and Egr-l. J. Biol. Chern. 277: 22222-22230.
2004 K. Chen, D. P. Holschneider, W. Wu, 1. Rebrin and 1. C. Shih. A spontaneous point mutation produces MAO A/B knockout mice with greatly elevated monoamines and anxiety-like behavior. J. Biol. Chern. Paper of the Week, 279(38): 39645-39652.
2005 K. Chen, X. M. Ou, W. Wu, G. Chen and J. C. Shih. RI, a novel repressor of the human monoamine oxidase A. J. BioI. Chern. 25: 11552-115529.
2006 Ou X, Chen K and Shih J: Monoamine oxidase A and repressor R1 are involved in apoptotic signaling pathway. Proc Natl Acad Sci U S A. 103:10923-1092.