The Chen Lab
                                                     

Our research is primarily focused on the following areas:

1) The molecular mechanisms underlying the assembly of the spinal dorsal horn circuitry. The dorsal spinal cord is a pivotal center for integrating and relaying signals such as pain, itch and temperature from the periphery to the brain. We have shown that several transcription factors including Drg11 and Lmx1b have important function in the development of the dorsal spinal cord.  Using genome-wide dorsal/ventral differential screenings, we have identified other dorsal lamina-specific genes, and are employing both conventional and conditional knockout approaches to dissect their function in the dorsal spinal cord.

2) The molecular mechanisms underlying the development of the central 5-HT system and the role of the 5-HT system in animal behaviors.  Serotonin (5-HT) is a key neurotransmitter implicated in numerous psychiatric and pathological disorders including pain, depression, aggression and anxiety.  We have identified Lmx1b as a critical gene for the development of all central 5-HT neurons.  Using a cre/loxP approach, we have generated a line of mice in which Lmx1b is deleted only in neurons expressing Pet1, a central 5-HT-specific transcription factor.  These mutant mice lack the central 5-HT system but show normal locomotive activity, and can be used as a unique animal model for studying the role of central 5-HT neurons in behaviors as well as the mechanism of action of some antidepressants.  

3) The molecular mechanisms underlying the itch sensation. Chronic itch, like chronic pain, affects human welfare.  Itch and pain are intimately related, and may share similar peripheral and central mechanisms. We have identified a gene called gastrin-releasing peptide receptor in the spinal cord.  Interestingly, we found that GRPR is required for relaying itch signals, but not pain signals. This suggests that there exists an itch-specific molecular pathway in the central nervous system.  In addition, we want to know how the itch sensation is modulated by descending pathways.  We are also interested in examining the relationship between pain and itch, which often exert opposing effects on animals.

Our multidisciplinary approach may reveal potential sites of drug actions on central pain and itch pathways and may aid in the new pharmacological strategies for pain and itch relief.