USC Addiction and Violence Research Center Jean C. Shih, Ph.D. School of Pharmacy University of...
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Transcript of USC Addiction and Violence Research Center Jean C. Shih, Ph.D. School of Pharmacy University of...
USC Addiction and Violence Research Center
Jean C. Shih, Ph.D.
School of Pharmacy University of Southern California
The First Structure of MAOB (Nat. Struc. Bol. 2002)
MAO A- inhibitor interaction
MAO B Gene Regulation
Stress Inflammatory cytokines growth factorsGrowth factors mitogens
PMA
PKC
Egr-1 c-Jun
MAO B Gene
cytoplasm
nucleus
MAPK Pathway
CACCC TATA
Sp1 / Sp4
Sp3 / BTEB2TIEG2
Sp3
MAO A KO mice MAO B KO mice
Wild type mice
MAO A/B doubleKO mice
MAO A KO mice
5-HT, NE, DA
aggression
Forebrain-specific transgenic MAO A KO mice
5-HT, NE, DA normal level in forebrain
No aggression
MAO B KO mice
PEA
No aggression
MAO A/B double KO mice
5-HT, NE, DA PEA
AnxietyDisregulation of heart rate
The increased 5-HT in forebrainis responsible for aggression
Different levels of 5-HT leadto different signaling pathwayswhich lead to different behaviors
USC Addiction and Violence Research CenterFor Studying the Cause, Treatment and Prevention
of Drug Abuse and Violence
Addiction: Social StudiesUsing 10,000 methamphetamine abusers*Demographics (gender, twins, ethnicity, type of substance,
criminal justice status)*Social factors (employment and environmental stressors)*Developmental factors (childhood development, maternal
smoking and substance use)
Y. Hser, UCLA
Addiction and Violence: Clinical Studies*Psychological traits
*Psychiatric diagnosis
(addiction, depression anxiety, aggression)
D. Holschneider, J. Victoroff USC Keck School of Medicine
DNA, SNP Mutation Discovery(Genes in serotonin and dopamine pathways)
J. Shih, K. Chen, USC School of Pharmacy
D. Conti, USC Keck School of Medicine
L. Baker, USC College of Letters, Arts & Sciences,
Psychology
BioinformaticsD. Conti
USC Keck School of Medicine
Animal Models (transgenic mice)
Metabolome (correlate brain and urine levels)
Behavior
K. Chen, USC School of Pharmacy
D. Holschneider, USC Keck School of Medicine
Education
J. Colbert, M. Sundt, USC School of Education
R. Aster, USC School of Social Worker
Neuro-imaging
A. Raine and others
USC College of Letters, Arts and Sciences, Psychology