The primary products of the genome are a vast array of proteins (the proteome) that codify the structure and function of cells throughout the body. This proteome represents a major post-genomic domain of organization in cells.  Our research centers on identifying and characterizing protein interaction networks for the dopamine and nicotinic acetylcholine receptors in the brain.  These receptors modulate neuronal activity associated with complex brain functions such as cognition and memory, and are implicated in the mechanisms of addiction as well as mental disorders such as schizophrenia.  Both receptor systems represent key molecular targets in pharmacological drug development and in biomarker discovery.

1. Proteomic and functional analysis of receptor interaction networks from cultured neurons and brain tissue

A Coomasie stained gel showing proteins that coimmunoprecipitate with the b2 subunit of the nicotinic receptor in the brain of wild type (+/+) and b2-knockout (-/-) mice. Arrowheads point gel bands excised for MS-MALDI-TOF analysis. Representative mass spectra for 2 identified proteins is shown on the right. Kabbani et al. (2007) PNAS.

2. Molecular profiling of drug effect in brain

Analysis of protein expression in the cortex following chronic treatment with the antipsychotic drugs Haloperidol and Clozapine. The average % change in total protein levels relative to vehicle for 6 dopamine receptor interacting proteins. Kabbani and Levenson (2006) Neuroreport.

3. Bioinformatic and structural analysis of receptor interactions

A structural model of the human D2 dopamine receptor generated using I-Tasser (Kansas University) showing transmembrane (TM) and intracellular (IC) regions.

Intracellular residues for protein interaction within the D2 dopamine receptor. Kabbani and Levenson (2007) Eur J Pharmacol.