Koon-Sea Hui, Ph.D., Director

Our laboratory studies the neurochemistry underlying mental health and disease by examining brain-specific proteins and neuropeptide metabolism. Brain-specific proteins are pivotal biomarkers and powerful tools for studying of neural mechanisms and neuropathology. Their functions have been identified in neurotransmitter metabolism, cell-to-cell recognition, differentiation, signal transduction, glycolysis, gene expression, receptors, ion channels, and the cytoskeleton. Focusing on neuropeptide metabolism, we were the first to find a brain-specific protein, BP-170, with increased expression in post-mortem schizophrenic brain.

The role of peptidases in neuropeptide inactivation has become evident; they offer a rational target for therapeutic intervention through modulation of their activity. Enkephalins are endogenous opioid peptides that modulate pain, anxiety, aggression, and immune response. The bioactive opioid peptides -- enkephalins, b-endorphin, dynorphin, and orphanin -- are inactivated by proteolytic metabolism. We aim to find the key enzyme that terminates enkephalin actions. Recent findings indicate a neuronal location associated with restricted substrate selectivity of a peptidase constitute a functional 'neuropeptidase'. Using a sensitive and specific aminopeptidase analyzer, we found a novel neuron-specific aminopeptidase exclusive to brain. The unique localization of the enzyme and its developmental expression profile imply a role in nociception, neuronal growth, and differentiation.

We are concurrently exploring the possibility of developing a new line of analgesics that are devoid of opiate's unwanted side-effects, including tolerance and physical dependence, in studying brain peptidases and their endogenous and synthetic inhibitors. We identified and characterized the first endogenous inhibitor (anti-enkephalinase) for enkephalin metabolism. We plan to find a potent inhibitor in the brain and to synthesize compounds that are innovative analgesics.

For further information, contact Dr. Hui at