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Cellular mechanisms of G protein-coupled receptor signaling in the modulation of anxiety, fear, and pain

thesis
posted on 17.02.2020, 17:00 by Mee Jung Ko

G protein-coupled receptors (GPCRs) are a large family of seven-transmembrane domain receptors that can be activated by endogenous and exogenous ligands including neuropeptides, hormones, and neurotransmitters. Approximately 30% of clinically marketed drugs are targeting GPCRs. Various GPCRs are involved in modulation of neurophysiological responses in the brain, suggesting that GPCRs serve as an important drug target for neurological disorders. Traditional GPCR pharmacology has focused on the canonical G protein-mediated signaling pathway of GPCRs, but increasing cellular evidence suggests that β-arrestin-mediated signaling pathways are also modulating GPCR signaling and affecting pathophysiological responses. Here, the present thesis aims to interrogate cellular mechanisms of β-arrestin-mediated signaling and its downstream kinase activity in behavioral modulation. I will also briefly examine β-arrestin-mediated ion channel modulation and developing in vivo tools for this unique modulation. Altogether, these studies advance understanding of GPCR signaling in distinct behavioral modulation and provide novel insights to therapeutic developments for neurological disorders targeting GPCRs.

Funding

National Institute on Alcohol Abuse and Alcoholism (AA025368)

NARSAD Young Investigator Award from the Brain and Behavior Research Foundation (#23603)

Purdue Research Foundation

History

Degree Type

Doctor of Philosophy

Department

Medicinal Chemistry and Molecular Pharmacology

Campus location

West Lafayette

Advisor/Supervisor/Committee Chair

Richard M. van Rijn

Additional Committee Member 2

Julia A. Chester

Additional Committee Member 3

Riyi Shi

Additional Committee Member 4

Edward L. Bartlett

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