Bioactive peptides; vesicles; enzymes; tissue culture; secretion; drug abuse.

Nearly every neuron in the brain secretes a biologically active peptide at its target cells along with one or more conventional neurotransmitters; many neurons secrete several bioactive peptides. Diversity in bioactive peptides is created by the existence of multiple closely related gene products encoding similar but not identical peptides, and by distinct patterns in post-translational processing of the propeptide precursors, so that a single peptide precursor gives rise to distinct peptide products in distinct tissues. The enzymes involved in peptide processing, and questions of how the peptide precursors and enzymes manage to find each other, to get together in the same secretory granules, are one focus of this lab group. We use a number of immortal cell lines in culture which express an endocrine phenotype, and we culture primary neurons and endocrine cells which behave in culture as well as the cells which remain in the intact animal.

The cultured cells allow us to manipulate the environment and the genes expressed by the cells, often in ways impossible in the whole animal. We transfect cells to introduce or knock out genes of interest, or we use viral vectors to infect primary cells and force them to make proteins that nature never intended. We also produce, in large quantities in fibroblast cell lines and bacteria, the proteins we express in smaller amounts in neurons and endocrine cells, to enable detailed enzymology to be performed.

Drugs of abuse, notably stimulants like cocaine, are another area of interest. We are interested in what genes are turned on and off in response to drugs of abuse, and which genes may be part of long-term responses to drugs such as addiction and withdrawal.

Not accepting lab rotation students at this time

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