Jean C. Shih, PhD
Faculty Directory

Jean C. ShihPhD

Jean C. ShihPhD

University Professor & Boyd & Elsie Welin Professor, Pharmacology and Pharmaceutical Sciences

Department of Pharmacology and Pharmaceutical Sciences

Jean Chen Shih received her BS in biochemistry from the National Taiwan University, where she graduated as the valedictorian. She earned her PhD in biochemistry from a joint program at the University of California, Riverside, and UCLA. She continued as a postdoctoral research fellow at UCLA and, in 1974, she joined the USC School of Pharmacy faculty.

Currently a University Professor, Shih holds the Boyd P. and Elsie D. Welin Professor of Pharmaceutical Sciences. She is the founding director of the USC–Taiwan Center for Translational Research. Shih’s numerous honors include two Research Scientist Awards and two MERIT awards from the National Institutes of Health (NIH), each providing 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, and the American College of Neuropsychopharmacology; a recipient of the Volwiler Research Achievement Award from the American Association of Colleges of Pharmacy; USC Associates Award for Creativity in Research and Scholarship; a Distinguished Series Kaiser Lecturer at University of Hawaii; and several other awards.

Shih has served as a member of NIH study sections in Psycho Clinical Biology, 1984-88, and Neurobiology, 1990-94; National Institute of Child Health and Human Development’s Mental Retardation Committee, 1997-2001; and the NIH Director and Pioneer Award review committee (2011-2014). She was a member of the International Brain Research Committee of the National Academy of Sciences (1995-2000). She is a current member and past president (2002-2004) of the Society of Chinese Bioscientists in America.

    Areas of Expertise

    • Novel Cancer Drug for both Therapy and Diagnosis
    • Repurposing Antidepressants for Brain Cancer
    • Repurposing Antidepressants for Prostate Cancer
    • Brain Development
    • Autism Spectrum Disorder
    • Education

      UC Riverside

      PhD

      National Taiwan University

      Biochemistry

    • Links
    • Research Focus

      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.

    • Selected Articles

      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.

      Read More

      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

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      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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    • Affiliations
      • Academia Sinica, Taiwan: Fellow

      • American College of Neuropsychopharmacology: Fellow

      • Department of Integrative Anatomical Sciences, Keck School of Medicine of USC

    • Accomplishments

      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

    • Research Grants

      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 Media Appearances

      USC study shows role of enzyme in prostate cancer growth

      USC News | 07/27/2018

      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 | 10/03/2017

      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 | 03/01/2016

      “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 | 07/15/2013

      "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 | 04/11/2013

      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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