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    Lori J Lorenz PhD

    TitleAssistant Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentProgram in Molecular Medicine
    AddressUniversity of Massachusetts Medical School
    373 Plantation Street
    Worcester MA 01605
    Phone508-856-2288
        Overview 
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        ACADEMIC BACKGROUND: Lori Lorenz received a B.S. in Biochemistry and Molecular Biology from Purdue University, and earned a Ph.D. in Biology with an NIH predoctoral fellowship to study circadian rhythms with Michael Rosbash at Brandeis University. She explored Drosophila genetics with Norbert Perrimon at Harvard Medical School through an NIH postdoctoral award, and became Instructor of Cell Biology with funding from the Taplin Foundation. In 2002, she came to the University of Massachusetts Medical School with a grant from the Whitehall Foundation to investigate mRNA translation in the nervous system. SCIENCE/TRANSLATION: We identified a gene that affects axon growth in Drosophila and found that the encoded protein, Neuroguidin, contains eIF4E-binding domains similar to those in proteins that inhibit mRNA translation (Jung et al., 2006). We found that Neuroguidin preferentially inhibits translation through a cytoplasmic polyadenylation element-binding site for the translation factor, CPEB. We also found that Neuroguidin regulates mRNA translation and synaptic plasticity in the rodent brain (Udagawa et al., 2012). SCIENCE/BEHAVIOR: Drosophila locomotor activity patterns entrain to light/dark environments similarly to humans, with higher levels during the day and lower levels at night. Genes controlling circadian rhythms vary in expression transcriptionally and continue to drive rhythmic behavior in subsequent darkness. Through transgenic GAL4/UAS and RNAi techniques, we find that homologs of Neuroguidin and CPEB (Orb) influence rest/activity patterns during entrainment, suggesting a role for translation in the generation of sleep/wake behavior or arousal. Hyper-excitability is common in autistic individuals upon silencing of the fragile X mental retardation gene, fmr1. Infertility due to loss of dfmr in flies is rescued by reduced orb (Costa et al., 2005). We find that reduced CPEB relieves electrophysiologic, developmental, and behavioral defects in a mouse model of fragile X syndrome (Udagawa et al., 2013), implicating an important role for translational homeostasis in normal brain function.

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        1. Udagawa T, Farny NG, Jakovcevski M, Kaphzan H, Alarcon JM, Anilkumar S, Ivshina M, Hurt JA, Nagaoka K, Nalavadi VC, Lorenz LJ, Bassell GJ, Akbarian S, Chattarji S, Klann E, Richter JD. Genetic and acute CPEB1 depletion ameliorate fragile X pathophysiology. Nat Med. 2013 Oct 20.
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        2. Udagawa T, Swanger SA, Takeuchi K, Kim JH, Nalavadi V, Shin J, Lorenz LJ, Zukin RS, Bassell GJ, Richter JD. Bidirectional Control of mRNA Translation and Synaptic Plasticity by the Cytoplasmic Polyadenylation Complex. Mol Cell. 2012 Jun 20.
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        3. Jung MY, Lorenz L, Richter JD. Translational control by neuroguidin, a eukaryotic initiation factor 4E and CPEB binding protein. Mol Cell Biol. 2006 Jun; 26(11):4277-87.
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        4. Richter JD, Lorenz LJ. Selective translation of mRNAs at synapses. Curr Opin Neurobiol. 2002 Jun; 12(3):300-4.
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        5. Van Vactor D, Lorenz LJ. Introduction: invertebrate axons find their way. Cell Mol Life Sci. 1999 Aug 30; 55(11):1355-7.
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        6. Van Vactor DV, Lorenz LJ. Neural development: The semantics of axon guidance. Curr Biol. 1999 Mar 25; 9(6):R201-4.
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        7. Eberl DF, Ren D, Feng G, Lorenz LJ, Van Vactor D, Hall LM. Genetic and developmental characterization of Dmca1D, a calcium channel alpha1 subunit gene in Drosophila melanogaster. Genetics. 1998 Mar; 148(3):1159-69.
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        8. Eberl DF, Lorenz LJ, Melnick MB, Sood V, Lasko P, Perrimon N. A new enhancer of position-effect variegation in Drosophila melanogaster encodes a putative RNA helicase that binds chromosomes and is regulated by the cell cycle. Genetics. 1997 Jul; 146(3):951-63.
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        9. Lorenz LJ, Hall JC, Rosbash M. Expression of a Drosophila mRNA is under circadian clock control during pupation. Development. 1989 Dec; 107(4):869-80.
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        10. Liu X, Lorenz L, Yu QN, Hall JC, Rosbash M. Spatial and temporal expression of the period gene in Drosophila melanogaster. Genes Dev. 1988 Feb; 2(2):228-38.
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        11. Deschenes RJ, Lorenz LJ, Haun RS, Roos BA, Collier KJ, Dixon JE. Cloning and sequence analysis of a cDNA encoding rat preprocholecystokinin. Proc Natl Acad Sci U S A. 1984 Feb; 81(3):726-30.
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        12. Dixon JE, Andrews PC, Collier K, Deschenes R, Funckes C, Lorenz L, Magazin M, Minth CD, Nichols R, Tavianini M, et al. Cloning and biosynthetic studies of rat somatostatin. Scand J Gastroenterol Suppl. 1983; 82:25-31.
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