Research Interests

Previous studies have used mass spectrometric methods with on-line chromatography to identify the Parkinsonian neurotoxin MPTP and characterize its metabolic transformation to MPP+; determine MPTP's mode of action in multiple species, including humans; characterize the metabolism of tryptophan to excitotoxic metabolites in the central nervous system; determine the elevated presence of quinolinic acid as a function of inflammatory processes in mammalian central nervous system; measure the kinetics of quinolinate and NAD formation; and identify glutamate as a factor in HIV-related excitotoxicity.

Our research seeks to provide means of preventing biological causes of neurodegenerative and neuropsychiatric disorders through understanding the molecular mechanisms of normal and aberrant cell development and the biochemical pathology of behavioral diseases. Healthy growth, proliferation and differentiation of cells require multiple sub-cellular complexes of proteins that provide specialized functions. Knowledge of the structural biology of normal and disease-related complexes can provide the basis to rationally define and treat the effects of disease. Our objective is to structurally characterize sub-cellular protein complexes in order to better understand and rationally treat human disease processes associated with impaired function. To achieve this objective, we are applying sub-cellular localization and bioinformatic proteomic methods to human cells grown in culture in collaboration with clinicians studying genetically characterized patients. A combination of chemical, molecular biological, immunological, and physical separation techniques are required to understand the intricate molecular interaction of functional sub-cellular units, genetically coded and comprised principally of proteins in highly ordered assemblies. The identity of individual protein units, their relative stoichiometry in an organelle, and the identity of posttranslational modifications that influence organellar functional activity are major challenges in unraveling how synapses function, as well as the effects of psychotropic drugs on synapses.