Julius Zhu, Ph.D., Principal Investigator
University of Virgina
$65,000 in 2004
$44,000 in 2003

By Katie Clapp, 3/2004

Dr. Zhu’s team is investigating synaptic plasticity in the Fragile X knockout mouse. They have found that two particular signaling pathways -- small GTPase Ras pathways -- are impaired in the knockout mouse. In these mice, they find very few of the AMPA receptors which are normally at synapses. Lack of AMPA receptors results in reduced synaptic plasticity in the Fragile X mice.

This research complements Dr. Elizabeth Berry-Kravis’s ongoing clinical trial of AMPAkines, compounds specifically designed to enhance the activity of AMPA receptors, so that each existing receptor is more effective. Dr. Zhu and his team are using physiological and molecular biological techniques to investigate the defects in Ras signaling and AMPA receptor trafficking in Fragile X mice. They will test whether Ras-GEF (a protein which activates Ras and is regulated by FMRP) can restore normal delivery of AMPA receptors to synapses. Their findings may point to promising targets for the design of new drugs to treat Fragile X.