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