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Our Group

The Center brings together three established investigators, Dr. Eric Klann (New York University), Dr. Gary Bassell (Emory University, Atlanta), and Dr. Joel Richter (UMass Chan Medical School), who each study translational control and its regulation in the mammalian brain. 

FRAGILE X TEAM IMAGE

Image from left to right: Dr. Eric Klann (New York University), Dr. Gary Bassell (Emory University, Atlanta), and Dr. Joel Richter. Also Dr. Manuel Garber and Dr. John L. Sullivan.

The central focus of our collaboration is to assess how re-balancing translational homeostasis in the diseased (FMRP lacking) brain ameliorates and indeed reverses the pathophysiology of FXS.

By either inhibiting or ablating key signaling molecules that lead to translation (PI3 kinase, Bassell; p70S6 kinase 1 (S6K1), Klann, or by ablating a translational control protein (CPEB, Richter in collaboration with Bassell and Klann), these investigators have rescued critical biochemical, morphological, physiological and behavioral phenotypes in Fmr1 null mice.

The purpose of the Center is to understand how modulation of the translational apparatus and upstream signaling pathways in the brain rescues FXS pathophysiology in mice.  The major goals are four-fold:  1) to use multiple genetic and pharmacologic murine models to determine the identities of mRNA molecules whose translation is rescued (i.e., restored to wild type levels) by alteration of the translational landscape, 2) to determine the importance of specific mRNAs for FXS whose translation is rescued, 3) to investigate the molecular mechanism by which translation is rescued, 4) to analyze human cells for rescue of translation and importance for FXS.