I am interested in the genetic regulation of NMDA receptor genes during the brain development. N-methyl-D-aspartate (NMDA) subtype of glutamate receptors participates in the formation of neuronal plasticity and migration of developing neurons, and is the major component of glutamate toxicity on neurons. My previous and ongoing work includes isolation and analysis of the NR1 and NR2A promoters; growth factor regulation and developmental activation of these promoters. I am also searching for key cis-elements and trans-factors important for developmental expression of the NMDA receptor genes. These studies may uncover factor(s) important for neuronal differentiation/maturation.

We are also interested in connecting signal pathways to the regulation of a specific gene via modifying selective nuclear proteins, such as, transcription factors. Using the glutamate receptor promoters as a model, we found that nerve growth factor activates Ras-MAP kinase and PI3 kinase pathways that modify Sp1 factor and in turn upregulating the NR1 promoter. Currently, we are looking for other novel transcription factors, such as single-stranded DNA binding proteins, as targets of growth factor signaling.

Molecular Mechanisms of Persistent Pain at Supral Spinal Cord Level. Collaborating with Drs. R. Dubner and K. Ren, we are interested in the role of glutamate receptors in the delivery of pain signals in the brainstem. Within the brainstem, neurons in the rostral ventromedical medullar (RVM) structure serve as a traffic center to send ascending pain signals to the brain cortex and descending pain signals to the spinal cord. Our research approach is to change the composition and protein structure of glutamate receptors in RVM neurons using transgene technologies, and thus to induce interference of pain sensation and hyperalgesia at spinal cord level in living animals.