We have been studying the roles of unconventional transmitters, like the d-amino acids in the central nervous system. We are particularly interested in the regulation of NMDARs by d-serine, a d-enantiomer previously thought to be restricted to bacteria or lower invertebrates. Work in our laboratory helped to establish d-serine as a major physiologic ligand for NMDARs that mediates NMDAR synaptic responses and neurotoxicity both in vitro and in vivo. In addition to neurotransmission, NMDARs also play a major role in neurodegeneration, and their excessive activation contributes to neuronal death in several neurodegenerative disorders, such as Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. In the past few years, we elucidated the mechanisms of d-serine synthesis by the enzyme serine racemase and discovered novel pathways regulating d-serine production and release from neural cells. We also discovered that d-serine is the dominant NMDAR co-agonist mediating neurotoxicity, raising the possibility that drugs that curb d-serine synthesis or release might be useful in neurodegenerative diseases where NMDARs are over-stimulated.
Our laboratory investigates several aspects of D-serine neurobiology utilizing molecular biology, biochemical, cell biology, mouse genetic models, and more recently electrophysiological techniques.
Candidates of all backgrounds and levels are welcome. They do not need previous experience in biochemistry or neuroscience but should be curious and fearless in challenging some cherished dogmas in the field.