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Jean C. Shih, PhD - USC School of Pharmacy. Los Angeles, CA, US

Jean C. Shih, PhD Jean C. Shih, PhD

University Professor & Boyd & Elsie Welin Professor, Pharmacology and Pharmaceutical Sciences | USC School of Pharmacy

Los Angeles, CA, UNITED STATES

Dr. Jean Chen Shih is one of the world’s leading researchers on the MAO enzymes and emotion behavior and cancers associated with this enzyme

Biography

Dr. Shih received her B.S. in biochemistry from the National Taiwan University, where she graduated as the valedictorian. She earned her Ph.D. in biochemistry from a joint program at the University of California, Riverside (UCR) and Los Angeles (UCLA). Dr. Shih continued as a postdoctoral research fellow at UCLA and, in 1974, she joined the School of Pharmacy faculty at USC.

She is currently a University Professor and holds the Boyd and Elsie Welin endowed chair. She is the founding Director of USC – Taiwan Center for Translational Research. She has received numerous honors: She received two Research Scientist Awards and two MERIT awards from the National Institutes of Health (NIH), each providing a 10-year support to investigators whose research competence and productivity are distinctly superior and who are likely to continue to perform in an outstanding manner. The MERIT award is given to the top 1% investigators of the country. She is a Fellow of Academia Sinica, Taiwan , Fellow of the American College of Neuropsychopharmacology; a recipient of the Volwiler Research Achievement Award from the American Association of Colleges of Pharmacy (AACP); USC. Associates Award for Creativity in Research and Scholarship; among many others. A Distinguish Series Kaiser Lecturer at University of Hawaii.

Dr. Shih is a member of the NIH study sections (Psycho Clinical Biology, 1984-88; Neurobiology, 1990-94; NICHD Mental Retardation Committee, 1997-2001). She is also a member of the International Brain Research Committee of the National Academy of Sciences (1995-2000). She is a current member and past president of the Society of Chinese Bioscientists in America (2002-2004). She is a mentor of American. NIH Director and Pioneer Award review committee (2011-2014).

Areas of Expertise (5)

Novel Cancer Drug for both Therapy and Diagnosis

Repurposing Antidepressants for Brain Cancer

Repurposing Antidepressants for Prostate Cancer

Brain Development

Autism Spectrum Disorder

Accomplishments (16)

MERIT Award (twice)

National Institutes of Health (NIH)

Research Scientist Award (twice)

National Institutes of Health (NIH)

MERIT Award

National Institute of Mental Health (NIMH)

Associates Award for Creativity in Research and Scholarship

USC

Volwiler Research Achievement Award

American Association of Colleges of Pharmacy (AACP)

Distinguish Series Kaiser Lecturer

University of Hawaii

President

Society of Chinese Bioscientists in America (SCBA)

Lifetime Achievement Award

Society of Chinese Bioscientists in America (SCBA)

President's Distinguished Lecturer

National Cheng Kung University, Taiwan

President's Distinguished Lecturer

Taipei Medical University, Taiwan

Distinguished Professor in Translational Research

Taipei Medical University, Taiwan

Fellow

American Association for the Advancement of Science (AAAS)

Fellow

The Honor Society of Phi Kappa Phi

Member

Phi Tau Phi Scholastic Honor Society of America

Member

Academia Sinica, Taiwan

Member

National Academy of Inventors

Education (2)

UC Riverside: Ph.D., Biochemistry

National Taiwan University: Biochemistry, B.S.

Affiliations (3)

  • Academia Sinica, Taiwan: Fellow
  • American College of Neuropsychopharmacology: Fellow
  • Department of Integrative Anatomical Sciences, Keck School of Medicine of USC

Selected Media Appearances (5)

USC study shows role of enzyme in prostate cancer growth

USC News  

2018-07-27

A new USC School of Pharmacy study led by University Professor Jean Chen Shih offers new evidence that the monoamine oxidase-A enzyme (MAO-A) pathway could be an important target in treating prostate cancer...

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USC study finds potential new treatments for Hodgkin’s lymphoma

USC News  

2017-10-03

The study was led by USC University Professor Jean C. Shih, whose pioneering research has provided insights into the enzyme’s effects on brain development, aggression, anxiety and autism spectrum disorders...

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Antidepressants may fight brain cancer

USC News  

2016-03-01

“Until now, patients diagnosed with these drug-resistant tumors have had no treatment options,” said University Professor Jean Chen Shih at the USC School of Pharmacy and the Keck School of Medicine of USC. “Antidepressants could be a potential treatment, slowing down the cancer growth and extending the lives of patients.”...

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Fear factor: Missing brain enzyme leads to abnormal levels of fear in mice, new research reveals

ScienceDaily  

2013-07-15

"These mice may serve as an interesting model to develop interventions to these neuropsychiatric disorders," said senior author Jean C. Shih, USC University Professor and Boyd & Elsie Welin Professor of Pharmacology and Pharmaceutical Sciences at the USC School of Pharmacy and the Keck School of Medicine of USC. "The severity of the changes in the MAO A/B knockout mice compared to MAO A knockout mice supports the idea that the severity of autistic-like features may be correlated to the amounts of monoamine levels, particularly at early developmental stages."...

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Trustee gives $1.5 million to research

Daily Trojan  

2013-04-11

Researchers at the center will focus on the development of pharmaceuticals to target monoamine oxidase (MAO), an enzyme suspected to hinder the spread of cancer. Jean Chen Shih, a professor in the School of Pharmacy and an expert in monoamine signaling, will lead the center...

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Research Focus (1)

The Shih Laboratory

Research objectives in the Shih Laboratory are to understand the roles of neurotransmitters on gene expression, signal transduction behaviors and ultimately diseases. They are studying the role of serotonin and dopamine in neuronal development, regulation of transcription factors in a series of monoamine oxidase (MAO) gene knock-out mice, which are animal models for anxiety, aggression and autistic-like-behavior and aggression. Recently, they showed these gene knockout mice also slowed down the progression and metastasis of prostate and brain cancers Thus provides unique animal models to study the interaction between tumors and microenvironment. Currently, Shih Lab used these KO mice model to develop novel targets for the treatment and early diagnosis of autistic-like behaviors and prostate and brain cancer.

Research Grants (5)

The Transcriptional Regulation of Monoamine Oxidase A

NIH/NIMH R01MH067968 

Aug 1, 2004 - Jun 30, 2010 Role: Principal Investigator

Molecular Studies of Monoamine Oxidases

NIH/NIMH R01MH067968 

Apr 1, 1989 - Apr 30, 2000 Role: Principal Investigator

Two Types of Monoamine Oxidase

NIH/NIMH R01MH039085 

Sep 1, 1985 - Nov 30, 2014 Role: Principal Investigator

Two Types of Monoamine Oxidase

NIH/NIMH R37MH039085 

Sep 1, 1985 - Dec 28, 2008 Role: Principal Investigator

Protein(s) Involved in Neurotransmission

NIH/NIMH R01MH037020 

May 1, 1982 - Dec 31, 2003 Role: Principal Investigator

Selected Articles (5)

Effect of Monoamine oxidase A (MAOA) inhibitors on androgen‐sensitive and castration‐resistant prostate cancer cells The Prostate

Shikha Gaur, Mitchell E Gross, Chun‐Peng Liao, Bin Qian, Jean C Shih

2019 Monoamine oxidase A (MAOA) is best known for its role in neuro‐transmitter regulation. Monoamine oxidase inhibitors are used to treat atypical depression. MAOA is highly expressed in high grade prostate cancer and modulates tumorigenesis and progression in prostate cancer. Here, we investigated the potential role of MAOA inhibitors (MAOAIs) in relation to the androgen receptor (AR) pathway and resistance to antiandrogen treatment in prostate cancer.nhibitors are used to treat atypical depression."

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Gene-environment interactions in antisocial behavior are mediated by early-life 5-HT2A receptor activation Neuropharmacology

Sean C Godar, Laura J Mosher, Simona Scheggi, Paola Devoto, Kelly M Moench, Hunter J Strathman, Cori M Jones, Roberto Frau, Miriam Melis, Carla Gambarana, Brent Wilkinson, M Graziella DeMontis, Stephen C Fowler, Marcelo P Coba, Cara L Wellman, Jean C Shih, Marco Bortolato

2019 The ontogeny of antisocial behavior (ASB) is rooted in complex gene-environment (G×E) interactions. The best-characterized of these interplays occurs between: a) low-activity alleles of the gene encoding monoamine oxidase A (MAOA), the main serotonin-degrading enzyme; and b) child maltreatment. The purpose of this study was to develop the first animal model of this G×E interaction, to help understand the neurobiological mechanisms of ASB and identify novel targets for its therapy. Maoa hypomorphic transgenic mice were exposed to an early-life stress regimen consisting of maternal separation and daily intraperitoneal saline injections and were then compared with their wild-type and non-stressed controls for ASB-related neurobehavioral phenotypes. Maoa hypomorphic mice subjected to stress from postnatal day (PND) 1 through 7 – but not during the second postnatal week - developed overt aggression, social deficits and abnormal stress responses from the fourth week onwards. On PND 8, these mice exhibited low resting heart rate - a well-established premorbid sign of ASB – and a significant and selective up-regulation of serotonin 5-HT2A receptors in the prefrontal cortex. Notably, both aggression and neonatal bradycardia were rescued by the 5-HT2 receptor antagonist ketanserin (1–3 mg kg−1, IP), as well as the selective 5-HT2A receptor blocker MDL-100,907 (volinanserin, 0.1–0.3 mg kg−1, IP) throughout the first postnatal week. These findings provide the first evidence of a molecular basis of G×E interactions in ASB and point to early-life 5-HT2A receptor activation as a key mechanism for the ontogeny of this condition.

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Gene-Environment Interactions in Antisocial Behavior Are Mediated by Early-Life 5-HT2A Receptor Activation Neuropharmacology

Godar SC, Mosher LJ, Scheggi S, Devoto P, Moench KM, Strathman HJ, Jones CM, Frau R, Melis M, Gambarana C, Wilkinson B, DeMontis MG, Fowler SC, Coba MP, Wellman CL, Shih JC, Bortolato M

2019 The ontogeny of antisocial behavior (ASB) is rooted in complex gene-environment (G×E) interactions. The best-characterized of these interplays occurs between: a) low-activity alleles of the gene encoding monoamine oxidase A (MAOA), the main serotonin-degrading enzyme; and b) child maltreatment. The purpose of this study was to develop the first animal model of this G×E interaction, to help understand the neurobiological mechanisms of ASB and identify novel targets for its therapy. Maoa hypomorphic transgenic mice were exposed to an early-life stress regimen consisting of maternal separation and daily intraperitoneal saline injections and were then compared with their wild-type and non-stressed controls for ASB-related neurobehavioral phenotypes. Maoa hypomorphic mice subjected to stress from postnatal day (PND) 1 through 7 - but not during the second postnatal week - developed overt aggression, social deficits and abnormal stress responses from the fourth week onwards. On PND 8, these mice exhibited low resting heart rate - a well-established premorbid sign of ASB - and a significant and selective up-regulation of serotonin 5-HT2A receptors in the prefrontal cortex. Notably, both aggression and neonatal bradycardia were rescued by the 5-HT2 receptor antagonist ketanserin (1-3 mg kg-1, IP), as well as the selective 5-HT2A receptor blocker MDL-100,907 (volinanserin, 0.1-0.3 mg kg-1, IP) throughout the first postnatal week. These findings provide the first evidence of a molecular basis of G×E interactions in ASB and point to early-life 5-HT2A receptor activation as a key mechanism for the ontogeny of this condition.

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SMAD2 As Risk Locus for Human Left Atrial Isomerism Detected by Mother-Fetus-Pair Exome Sequencing and Imaging Studies Ultrasound in Obstetrics & Gynecology

Shih JC, Ma GC, Cheng WC, Chen CY, Wu WJ, Chen M

2019

R1 Regulates Prostate Tumor Growth and Progression By Transcriptional Suppression of the E3 Ligase HUWE1 to Stabilize c-Myc Molecular Cancer Research

Tzu-Ping Lin, Jingjing Li, Qinlong Li, Xiangyan Li, Chunyan Liu, Ni Zeng, Jen-Ming Huang, Gina Chia-Yi Chu, Chi-Hung Lin, Haiyen E Zhau, Leland WK Chung, Boyang Jason Wu, Jean C Shih

2018 Prostate cancer is a prevalent public health problem, especially because noncutaneous advanced malignant forms significantly affect the lifespan and quality of life of men worldwide. New therapeutic targets and approaches are urgently needed. The current study reports elevated expression of R1 (CDCA7L/RAM2/JPO2), a c-Myc–interacting protein and transcription factor, in human prostate cancer tissue specimens. In a clinical cohort, high R1 expression is associated with disease recurrence and decreased patient survival. Overexpression and knockdown of R1 in human prostate cancer cells indicate that R1 induces cell proliferation and colony formation. Moreover, silencing R1 dramatically reduces the growth of prostate tumor xenografts in mice. Mechanistically, R1 increases c-Myc protein stability by inhibiting ubiquitination and proteolysis through transcriptional suppression of HUWE1, a c-Myc–targeting E3 ligase, via direct interaction with a binding element in the promoter. Moreover, transcriptional repression is supported by a negative coexpression correlation between R1 and HUWE1 in a prostate cancer clinical dataset. Collectively, these findings, for the first time, characterize the contribution of R1 to prostate cancer pathogenesis.

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