Angus Clark Nairn PhD
Charles B. G. Murphy Professor of Psychiatry and Professor of Pharmacology
Dopaminergic signal transduction; Structure and function of protein kinases and phosphatases
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 incites 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.