Angus Clark Nairn, PhD

Charles B. G. Murphy Professor of Psychiatry and Professor of Pharmacology

Research Organizations

Interdepartmental Neuroscience Program

Neuroscience Microarray Center, Yale

NIDA Neuroproteomics Center

Psychiatry: Connecticut Mental Health Center | Molecular Psychiatry, Division of | Specialized Center of Research (SCOR) to Develop Gender-Sensitive Treatment for Tobacco Dependence | Stress & Addiction Clinical Research Program

Research Summary

Our research is focused on the molecular actions of dopamine in the basal ganglia. The disruption of normal dopaminergic neurotransmission is known to underlie certain neurological diseases, including Huntington's and Parkinson's disease, schizophrenia and attention deficit hyperactivity disorder. Modulation of dopamine-regulated signaling pathways is also likely to play an important role in the addictive actions of various drugs of abuse. Our studies of basal ganglia phosphoproteins will hopefully provide insights into how dopaminergic neurotransmission is altered in various diseases models and also to provide a rational new approach to developing drugs that specifically affect these phosphoproteins or their targets.

Extensive Research Description

Our discovery and characterization of striatal phosphoproteins controlled by dopamine, including DARPP-32, RCS, and ARPP-16, provides a rational approach to the elucidation of the molecular actions of dopamine. Our current studies focus on the biochemical characterization of DARPP-32 and its target, protein phosphatase-1, on RCS and the regulation of calmodulin-dependent signaling, and on ARPP-16 and its potential involvement in regulation of protein phosphatase 2A. In these studies we utilize we use biochemical, molecular, and cell biological methods to characterize the role of these proteins in signal transduction pathways in striatal neurons. In addition, we use mouse models where striatal phosphoproteins and their targets have been “knocked out” to investigate the functions of these dopamine-regulated pathways in a variety of behavioral paradigms. Other interests of the laboratory include the signaling processes that regulate the F-actin cytoskeleton in dendritic spines.

cAMP-regulated signal transduction in striatal neurons.

Proteomics of specific neuronal populations.

Selective regulation of protein translation.

Selected Publications

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Contact Info

Angus Clark Nairn, PhD
Mailing Address
Department of Psychiatry300 George St
New Haven, CT 06511-
Research Image 2

Beyond the Dopamine Receptor: Regulation and Roles of Serine/Threonine Protein Phosphatases: Left Panels: DARPP-32 (left, saggital section, positive immunoreactivity black), RCS (middle, coronal section, positive immunoreactivity white; caudate/putamen (CP) and nucleus accumbens (A); inset at right shows RCS enrichment in nucleus accumbens (left of dashed line) in more rostral section, ARPP-16 (right, saggital section, immunoreactivity white). Simple domain diagrams of each protein with their amino acid number and site of PKA phosphorylation are shown below the respective immunolocalization panels. Right Panel: Interactive roles of DARPP-32, RCS and ARPP-16 in regulation of signal transduction in striatal neurons.