Justin R. FallonProfessor of Medical Science, Professor of Psychiatry and Human Behavior
Justin Fallon is a Professor of Neuroscience and Co-Director of the Center for the Neurobiology of Cells and Synapses at Brown University. He also founded Tivorsan Pharmaceuticals, a biotech company dedicated to developing therapies for Muscular Dystrophy and ALS. His original training was in cell biology the University of Pennsylvania. He then expanded into neurobiology during postdoctoral training at University College London and Stanford. His work led to the discovery of biglycan, a protein that stabilizes the nerve-muscle synapse and controls a key pathway that can compensate for the underlying defect that causes Duchenne Muscular Dystrophy. Fallon also studies the mechanisms of enduring synaptic plastic and how they are defective, and can be corrected, in neurodevelopmental disorders such as Autism.
Our lab has two major interests. Duchenne muscular dystrophy strikes one in 3,000 boys. Our basic research led to the discovery that the extracellular protein biglycan regulates an intrinsic cellular pathway that can compensate for the genetic defect in Duchenne. We are currently developing recombinant biglycan as a therapeutic for Duchenne. Biglycan also holds promise as a therapy for ALS and Congenital Muscular Dystrophy.
Second, how do we learn, and why are we so good at it when we are young? Using Fragile X mental retardation as a model, we seek to understand how ephemeral episodes of experience are transformed into stable changes in synaptic architecture and efficacy. We are particularly interested in how local RNA translation in axons shapes brain circuitry and function.
A novel therapy for Muscular Dystrophy
Our lab is working to develop a novel therapy for Duchenne's muscular dystrophy, which strikes one in 3,000 boys. In previous work we are characterized a new extracellular component of the dystrophin complex, a critical ensemble of proteins that is defective in people with this disease. Our recent findings indicate that this component, biglycan is important for signaling at both the neuromuscular junction and at the dystrophin complex. We are currently testing the efficacy of biglycan in mouse models of Duchenne's Muscular Dystrophy. Our results have been very encouraging and we are now working to bring biglycan therapy into the clinic.Learning and Memory:
The Fragile X system: Mental retardation and Autism
In the second area we study how experience shapes neural circuitry. This process is fundamental to learning, memory and forging effective communication between self and the outside world. Our focus is on Fragile X syndrome, which is both the most prevalent inherited mental retardation and the most common single gene cause of autism (or Autism Spectrum Disorders; ASD). Recent evidence indicates that the behavioral parallels between FXS and autism reflect shared cellular mechanisms: both conditions are disorders of synaptic plasticity. In both diseases it is likely that there is failure of appropriate sculpting of neural circuitry in response to environment/experience. We have discovered a novel structure, the Fragile X Granule (FXG) that is expressed presynaptically. Intriguingly, FXGs are circuit selective and developmentally regulated. The distribution and timing of these granules correlates remarkably well with circuits known to be affected in autism such as prefrontal cortex, cerbellum and limbic system. Our working hypothesis is that FXGs are involved in presynaptic plasticity and axonal pruning. Current projects in the lab include the selective manipulation of presynaptic FMRP/FXGs using Cre-lox methodology in vivo and compartmentalized cultures where we can isolate axonal fractions. Our goals are: 1) To identify the RNA cargo of FXGs; 2) To determine the protein composition of FXGs; 3) To demonstrate the function of FXGs in synaptic plasticity.
NIH 1U01NS064295-04. "Development of biglycan as a therapeutic for Duchenne Muscular Dystrophy". Justin Fallon, Principal Investigator. 8/1/09 – 6/30/15.
1973- Honors in Biology, Colgate University
1980-83 National Institutes of Health Postdoctoral Fellow, National Research Service Award
1983-84 Dysautonomia Foundation, Postdoctoral Fellow,
1989-91 March of Dimes, Basil O'Connor Starter Research Scholar Award
2003- Associate Editor, Journal of Cellular Physiology
2004- Member, Scientific Advisory Board, Fragile X Research Foundation (FRAXA)
2006- Member, Scientific Advisory Board, Charley's Fund
2008 EndDuchenne Prize, Parents Project Muscular Dystrophy
2013 Editorial Board, Journal of Neuromuscular Diseases
Society for Neuroscience
American Society for Cell Biology
We are in the midst of a revolution in our understanding of neurological and psychiatric disease. A confluence of genetic, imaging, and cell biological approaches is bringing to light the underlying causes and pathology of a host of brain and nervous system disorders. The goals of this course are to illustrate what basic science can teach us about disease and how these pathologies illuminate the functioning of the normal nervous system. Consideration will be given to monoallelic diseases (e.g. Fragile X Syndrome, Duchenne Muscular Dystrophy and Tuberous Sclerosis) as well as genetically complex disorders where genome-environment interactions seem likely to contribute to the pathology e.g. Autism and Alzheimer's Disease). Emphasis will be on the cellular and molecular basis of these disorders and how insights at these levels might lead to the development of therapies.
NEUR 1740 - The Diseased Brain: Mechanisms of Neurological and Psychiatric Disorders. Spring 2014, Spring 2015.
NEUR 1930G - Disease, Mechanism, Therapy: Harnessing Basic Biology for Therapeutic Development. Fall 2013.
NEUR 2040 - Advanced Molecular and Cellular Neurobiology II. Spring 2016.