Research in my laboratory focuses on developing and implementing an array of novel mass spectrometry based strategies to answer questions about the most complex and elusive set of signaling molecules, the neuropeptides, and gain new insights into the roles of peptide hormones and neurotransmitters play in the plasticity of neural circuits and behavior. While significant effort has been directed to analytical technique and method development, it is the biomedical importance of understanding the neuropeptidergic system that drives our research to continuously refine and improve the analytical capabilities to address challenging neuroscience problems. Specifically, we are interested in understanding the roles that neuropeptides play in food intake, neural network development and response to environmental stresses. We have chosen to work with a simpler and well-defined crustacean nervous system to both facilitate technology development and address fundamental neuroscience problems related to neuromodulation and network plasticity. We have developed several unique sample preparation strategies and instrumentation protocols that enable sensitive analysis of neuropeptides directly from minute quantities of neural tissues. By combining chemical labeling, micro-scale separation, and tandem mass spectrometry sequencing techniques, we have discovered a large number of novel neuropeptides used in crustacean nervous systems. The physiological effects of these new peptides at the cellular and network levels are evaluated in collaboration with laboratories of Eve Marder and Michael Nusbaum. Furthermore, both mass spectrometric imaging techniques and in vivo microdialysis sampling tools have been implemented to follow neuropeptide distribution and secretion with unprecedented details. Finally, a differential display strategy in conjunction with isotopic labeling technique is being developed to allow functional discovery of neuropeptides in response to various physiological changes. While the technology is developed using crustacean model system as a test-bed, the technology advancement resulting from our research is widely applicable to the large-scale analysis of peptides and proteins in many biological systems, including those of mammalian and humans. Towards this end, we have established several exciting collaborations targeted at neurochemical analysis in mammalian systems. These collaborative projects include the discovery of prion disease biomarkers in cerebral spinal fluids and serum (in collaboration with Judd Aiken and David Page), proteomic analysis neuroprotective factors secreted by astrocytes (in collaboration with Jeff Johnson), and proteomic study of dioxin-induced cardiotoxicity in developing zebrafish (in collaboration with Warren Heideman and Dick Peterson). We are also interested in developing new collaborations to help transform advances in analytical tools into important findings that lead to new diagnosis and therapeutic strategies.