Research & Publications
Our research is focused on the molecular actions of dopamine in the striatum. Dopamine plays a key role in goal-directed behavior, as well as in reward and habit learning. The disruption of normal dopaminergic neurotransmission is known to underlie certain neuroodegenerative and neuropsychiatric diseases, including Huntington's and Parkinson's disease, and schizophrenia. Modulation of dopamine-regulated signaling pathways also plays an important role in the addictive actions of various drugs of abuse. Our studies of dopamine-dependent signal transduction in striatal neurons provide novel insights into how dopaminergic neurotransmission is altered in various diseases models and also provides a rational new approach to developing drugs that specifically affect these signaling pathways. An important component of our research is the development of biochemical methods to interrogate alterations in protein expression and regulation in specific neuronal cell types using novel proteomic approaches.
Specialized Terms: signal transduction; Structure and function of protein kinases and phosphatases
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.
cAMP-regulated signal transduction in striatal neurons.
Proteomics of specific neuronal populations.
Selective regulation of protein translation.
Dopamine; Huntington Disease; Parkinson Disease; Protein Kinases; Psychiatry; Schizophrenia; Signal Transduction