Ph.D., University of Pennsylvania
Professor
Department of Neuroscience
358 Sidney Frank Hall of Life Sciences
Tel: (401) 863-9308
Email: Justin_Fallon@Brown.edu
Go to lab web page

Learning and Memory: Fragile X Syndrome, Chromatin Structure and the Olfactory System

How do we learn, and why are we so good at it when we are young?  A fundamental problem in neuroscience is understanding how ephemeral episodes of experience are transformed into stable changes in synaptic architecture and efficacy.  The creation of such long-lasting synaptic modifications requires new protein synthesis, which in turn is regulated at both  transcriptional and translational levels.  Moreover, the transcriptional repertoire of the neuron is a function of its developmental stage –  in particular the critical period – and its history of activation.  A major challenge in unraveling the mechanisms of long term plasticity then is to relate both developmental timing and experience-induced neural activity to the regulation of identified molecules that play key roles in synaptic plasticity.  Fragile X Syndrome (FXS), the most common form of inherited mental retardation, offers a portal to the heart of this problem. The protein product of the Fmr1 gene, FMRP, plays a central role in regulating protein synthesis-dependent synaptic plasticity.  We have found that Fmr1 transcripts are highly abundant in the developing and adult olfactory bulb and are bi-directionally regulated by olfactory experience.  Moreover, we have found that the chromatin structure of the Fmr1 promoter region is developmentally regulated.  We are using genetic, cellular and molecular approaches to understand the interplay of synaptic activity and gene expression in shaping neuronal architecture and function.

Muscular Dystrophy

In other research, our lab is working to understand Duchenne's muscular dystrophy, which strikes one in 3,000 boys.  We are characterizing the structure and function of the dystrophin complex, a critical ensemble of proteins that is defective in people with this disease.  We have identified a new member of this complex, the proteoglycan biglycan.  Our recent findings indicate that biglycan is important for signaling at both the neuromuscular junction and at the dystrophin complex.  Our goals are to elucidate biglycan function in normal muscle and to use these insights to design novel therapeutics for muscular dystrophy.

Taylor, A.B., and J.R. Fallon. (2006) Dendrites contain a spacing pattern. J Neurosci. 26:1154-63.

Rafii, M.S., H. Hagiwara, M.L. Mercado, N.S. Seo, T. Xu, T. Dugan, M. Hook, D.J. McQuillan, M.F. Young and J.R. Fallon. (2006) Biglycan is a ligand for alpha- and gamma- sarcoglycan and is associated with the dystrophin glycoprotein complex. J. Cell. Physiol. 209:439-47.

Mercado, M.L., A. R. Amenta, H. Hagiwara, M. S. Rafii, R. T. Owens, D. J. McQuillan and J.R. Fallon. (2006) Biglycan targets dystrobrevin, syntrophin and nNOS to the muscle cell membrane FASEB J. 20:1724-6. Epub 2006 Jun 28.

Lim, J.H., A.B. Booker ,T. Luo, T. Williams, Y. Furuta, O. Lagutin, G. Oliver, T. D. Sargent, and J. R. Fallon  (2005) AP-2a selectively regulates fragile X mental retardation-1 gene transcription during embryonic development  Hum. Mol. Genetics. 14:2027-34.

Lim, J.H., A.B. Booker, J.R. Fallon. (2005) Regulating fragile X gene transcription in the brain and beyond.  J. Cell. Physiol. 205:170-175.

Lim, J.H., T. Luo, Y. Zhang, T. D. Sargent, and J. R. Fallon  (2005)  Developmental expression of Xenopus Fragile X mental retardation-1 gene.  Int. J. Dev. Biol. 49:981-84

Gabel, L.A. , S. Won, H. Kawai, M. McKinney, A. M. Tartakoff, and J. R. Fallon.  Visual experience induces a transient, NMDA receptor-dependent upregulation of Fragile X mental retardation protein in the visual cortex (2004).  J. Neurosci. 24:10579-10583.

Megeath, L.J., M.T. Kirber, C. Hopf, W. Hoch, and J.R. Fallon. (2003) Calcium-dependent maintenance of agrin-induced postsynaptic specializations. Neuroscience. 122:659-68.

Wells, D.G.,  X. Dong, . E.M. Quinlan, Y-S. Huang, M.F. Bear, J.D. Richter and J.R. Fallon (2001)  A Role for the Cytoplasmic Polyadenylation element in NMDA Receptor-Regulated mRNA Translation in neurons. J. Neuroscience21: 9541-48.

Snyder, E.M., B.D. Philpot, K.M. Huber, X. Dong, J.R. Fallon and M.F. Bear. (2001). Internalization of ionotropic glutamate receptors in response to mGluR activation.  Nat Neurosci. 4:1079-1085.

Bowe, M.A., Mendis, D. B., and Fallon, J.R. (2000)  The small leucine-rich repeat proteoglycan biglycan binds to a-dystroglycan and is upregulated in dystrophic muscle.  J. Cell Biol. 148: 801-810.

Lisman, J.E., and J.R. Fallon (1999)  What maintains memories?  Science  283: 339-340.