The general research focus of the lab is the elucidation of the neurobiological substrates of complex mammalian behaviors. Currently, our research focuses on the dysregulation of glutamate neurotransmission in neuropsychiatric disorders, principally substance abuse and schizophrenia. Ongoing projects in the lab include the following assessments of splice variation and RNA editing of ionotropic glutamate receptor subunits, histone modifications, promoter methylation and microRNA influences on mRNA and protein expression, and functional proteomic analysis of the post-synaptic density in these disease states.

Specific projects include:

Determination of cortical and subcortical molecular pathology associated with schizophrenia using post-mortem brain tissue from individuals diagnosed with schizophrenia. Recent efforts in this area focus on mechanisms of altered glutamate transmission in the entorhinal cortex, superior temporal gyrus and dorsolateral prefrontal cortex. Gene and protein expression patterns in humans are compared with analogous brain regions in rhesus monkeys treated chronically with typical and atypical antipsychotics.

Identification of gene and protein expression profiles of orbitofrontal cortex and regions of the mesolimbic and nigrostriatal dopamine pathways in post-mortem brain tissue from cocaine overdose victims and parallel studies in rhesus monkey and rat models of cocaine self-administration. Major focus is on alterations in ionotropic glutamate receptors in these regions.

Evaluation of the molecular neuropathology of long-term alcohol intake in post-mortem brain tissue of alcoholics and non-human primate models of alcohol self-administration with particular focus on the regulation of GABA and glutamate transmission in the orbitofrontal cortex and mechanisms of Purkinje cell loss in the cerebellum.

Our efforts are multi-disciplinary and require collaborations with several outstanding laboratories (see Collaborators) and various experimental approaches in our lab   including gene expression profiling of brain regions and discrete cell populations using whole genome microarrays, quantitative PCR, laser capture microdissection, proteomic profiling of discrete brain regions and protein fractions (e.g. post-synaptic density, nuclear, etc.) using multidimensional nano-HPLC, two dimensional gel electrophoresis, peptide mass fingerprinting, MALDI ToF/ToF mass spectrometry, capillary electrophoresis with laser induced fluorescence, immunohistochemistry and Western blotting.

Results from these projects will further our understanding of the biological basis of addictive disorders and schizophrenia and provide molecular "fingerprint" of these disorders which could provide novel targets for pharmacotherapeutic intervention. Current and future research will focus on the molecular phenotype of the targeted neurons, how complex cellular mechanisms are disrupted in disease states and how behavior modulates gene expression.