Melissa J. Moore, PhD
Professor and HHMI Investigator
Department of Biochemistry and Molecular Pharmacology
Co-Director, RNA and Neuro-therapeutics Institutes
mail University of Massachusetts Medical School
368 Plantation Street
Worcester, MA 01605
Faculty page: http://profiles.umassmed.edu/profiles/ProfileDetails.aspx?From=SE&Person=1083
Lab website: http://www.umassmed.edu/moorelab/
Research in my laboratory encompasses a broad array of post-transcriptional gene regulatory mechanisms involving RNA and RNA-protein complexes. Projects with particular relevance to neurodegenerative disease and development of novel therapeutics for treatment of such disorders include: (1) Elucidation of the mechanisms underlying maintenance of protein homeostasis for the RNA-binding proteins FUS/TLS and TDP-43, both of which have been directly implicated as causative agents of ALS and other neurodegenerative disorders; (2) Investigation into the effects on translation kinetics and mRNA stability imparted by extended trinucleotide repeats (e.g., the CAG repeats associated with Huntington's disease) within mRNA open reading frames; (3) Use of cell based screens to identify small molecules that modulate RNA metabolism.
Speese S, Ashley J, Jokhi V, Nunnari J, Barria R, Ataman B, Koon A, Chang Y-T, Li Qian, Moore MJ* and Budnik V* (2012) Nuclear envelope budding enables ribonucleoprotein particle export during synaptic Wnt signaling. Cell, 149, 832-846, May 11. (* co-corresponding authors)
Wu C, Fallini C, Ticozzi N, Keagle P, Sapp PC, Piotrowska K, Lowe P, Koppers M, McKenna-Yasek D, Baron D, Gonzalez-Perez P, Fox A, Adams J, Taroni F, Tiloca C, Leclerc AL, Chafe SC, Mangroo D, Moore MJ, Zitzewitz JA, Xu Z, van den Berg LH, Glass JD, Drory VE, Rossoll W, Ratti A, Gellera C, Bosco DA, Bassell GJ, Silani V, Brown RH and Landers JE. (2012) Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature, 48, 499-503, 23 August.
Aronin N and Moore MJ. (2012) Hunting Down Huntingtin. NEJM, 367(18); 1753-1754; November. PMID: 23113488.
Jokhi V, Ashley J, Nummari J, Noma A, Ito N, Wakabayashi-Ito N, Moore MJ and Budnik V. (2013). Torsin mediates primary envelopment of large ribonuclear granules at the nuclear envelope. Cell Reports,April 10.
Zhang Z, Almeida S, Lu Y, Nishimura AL, Peng L, Sun D, Wu B, Karydas AM, Tartaglia MC, Fong JC, Miler BL, Farese RV Jr, Moore MJ, Shaw CE, Gao FB. (2013). Downregulation of microRNA-9 in iPSC-derived neurons of FTD/ALS patients with TDP-43 mutations. PLoS One, October 15.
Yang C, Wang H, Qiao T, Yang B, Aliaga L, Qiu L, Tan W, Salameh J, McKenna-Yasek DM, Smith T, Peng L, Moore MJ, Brown Jr. RH, Cai H and Xu Z. (2014) Partial loss of TDP-43 function causes phenotypes of amyotrophic lateral sclerosis. PNAS, March 25.
Le Hir H, Nott A and Moore MJ (2003) How introns influence and enhance eukaryotic gene expression. TIBS, 28: 215-220.
Moore MJ (2005) From birth to death: The complex lives of eukaryotic mRNAs. Science, 309:1514-8.
Giorgi C, Yeo G, Stone ME, Katz DB, Burge CB, Turrigiano GG and Moore MJ. (2007) The EJC factor eIF4AIII modulates synaptic strength and neuronal protein expression. Cell, 130: 179-191.
Giorgi C and Moore MJ (2007) The nuclear nurture and cytoplasmic nature of localized mRNPs. Semin Cell Dev Biol. 18: 186-93.
Bramham CR, Worley PF, Moore MJ and Guzowski JF (2008) The immediate early gene arc/arg3.1: regulation, mechanism and functions. J Neurosci, 12: 11760-7.
O'Brien K, Matlin AJ, Lowell A and Moore MJ. (2008) The biflavonoid isogenkgetin is a general inhibitor of pre-mRNA splicing. J Biol Chem, 283: 33147-54.
Moore MJ and Proudfoot N (2009) Pre-mRNA processing reaches back to transcription and ahead to translation. Cell 136: 688-700.
Albert B, McPherson P, O’Brien K, Czaicki N, DeStefino V, Osman S, Li M, Day B, Grabowski P, Moore MJ, Vogt A and Koide K (2009). Meayamycin Inhibits pre-mRNA Splicing and Exhibits Picomolar Activity Against Multidrug Resistant Cells. Molecular Cancer Therapeutics 8: 2308-2318.
Lemmens R, Moore MJ, Al-Chalabi A, Brown RH Jr, Robberecht W (2010) RNA metabolism and the pathogenesis of motor neuron diseases. Trends Neuroscience 33: 249-58.
Moore MJ and Flotte TR. (2010) Autoimmunity in a Genetic Disease – Spontaneous Reversion for Priming a Response. NEJM, 363; 15.
Sephton CF, Cenik C, Kucukural A, Dammer EB, Cenik B, Han Y, Dewey CM, Roth FP, Herz, J, Peng J, Moore MJ, and Yu G. (2011) Identification of neuronal RNA targets of TDP-43-containing Ribonucleoprotein complexes. J Biol Chem 286: 1204-15.