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2017 News

DECEMBER 27, 2017, New publication from the Pai lab. The kinetics of pre-mRNA splicing in the Drosophila genome and the influence of gene architecture. Pai AA, Henriques T, McCue K, Burkholder A, Adelman K, Burge CB. Elife. 2017 Dec 27;6. pii: e32537. doi: 10.7554/eLife.32537.

Structural dynamics protein S1 70s Ribosome ensemble cryo-emDECEMBER 13, 2017, New publication from the Korostelev lab.  Structural dynamics of protein S1 on the 70S ribosome visualized by ensemble cryo-EM.  Loveland AB, Korostelev AA. Methods. 2017 Dec 13. pii: S1046-2023(17)30290-6. doi: 10.1016/j.ymeth.2017.12.004. 

arthropod piRNA analysis transposable elementsDECEMBER 11, 2017, New publication from the Zamore lab. Pan-arthropod analysis reveals somatic piRNAs as an ancestral defense against transposable elements. Lewis SH, Quarles KA, Yang Y, Tanguy M, Frézal L, Smith SA, Sharma PP, Cordaux R, Gilbert C, Giraud I, Collins DH, Zamore PD, Miska EA, Sarkies P, Jiggins FM. Nat Ecol Evol. 2017 Dec 4. doi: 10.1038/s41559-017-0403-4. 

miRNA rAAV reduces mutant Huntingtin mRNA in transgenic sheep modelDECEMBER 5, 2017, New publication from the Aronin lab. Artificial miRNAs reduce human mutant Huntingtin throughout the striatum in a transgenic sheep model of Huntington's disease. Pfister E, Dinardo N, Mondo E, Borel F, Conroy F, Fraser C, Gernoux G, Han X, Hu D, Johnson E, Kennington L, Liu P, Reid S, Sapp E, Vodicka P, Kuchel T, Morton AJ, Howland D, Moser R, Sena-Esteves M, Gao G, Mueller C, DiFiglia M, Aronin N. Hum Gene Ther. 2017 Dec 5. doi: 10.1089/hum.2017.199. 

type II CRISPR DECEMBER 4, 2017, New publication from the Sontheimer lab. Type II-C CRISPR-Cas9 Biology, Mechanism and Application. Mir A, Edraki A, Lee J, Sontheimer EJ. ACS Chem Biol. 2017 Dec 4. doi: 10.1021/acschembio.7b00855. 


Chitosan-Mangafodipir nanoparticles designed for intranasal delivery of siRNA and DNA to brainNOVEMBER 21, 2017, New publication from the Aronin & Khvorova labs. Chitosan-Mangafodipir nanoparticles designed for the intranasal delivery of siRNA and DNA to the brain. 
Sanchez-Ramos J, Song S, Kong X, Foroutan P, Martinez G, Dominguez-Viqueria W, Mohapatra S, Mohapatra S, Haraszti RA, Khvorova A, Aronin N, Sava V. J Drug Deliv Sci Technol. 2018 Feb;43:453-460. doi: 10.1016/j.jddst.2017.11.013. Epub 2017 Nov 21.

modifications to guide RNA in vivo genome editingNOVEMBER 13, 2017, New publication from the Xue lab. Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing. Yin H, Song CQ, Suresh S,  Wu Q, Walsh S, Rhym LH, Mintzer E, Bolukbasi MF, Zhu LJ, Kauffman K, Mou H, Oberholzer A, Ding J, Kwan SY, Bogorad RL, Zatsepin T, Koteliansky V, Wolfe SA, Xue W, Langer R & Anderson DG. For more on this paper, click here.

Melissa Moore Symposium Group PictureOCTOBER 25-26, 2017,  Symposium to be held in honor of Melissa Moore's academic career. See Moore Lab homepage for the announcement.


Erik Sontheimer Andrei KorostelevOCTOBER 20, 2017, Congrats to both Andrei Korostelev & Erik Sontheimer for receiving
awards! Andrei will be recognized for the Early-Career Award and Erik will be recognized for the Mid-Career Award! Story headlining UMassMedNow here, and announcement on The RNA Society's website here.

RNA Polymerase bound to 30s Ribosomal Subunit OCTOBER 13, 2017, New publication from the Korostelev lab. Structure of RNA polymerase bound to ribosomal 30S subunit. Demo G, Rasouly A, Vasilyev N, Svetlov V, Loveland AB, Diaz-Avalos R, Grigorieff N, Nudler E, Korostelev A. eLife 2017;6:e28560 DOI: 10.7554/eLife.28560

Pharmacokinetic Profiling of Conjugated Therapeutic OligonucleotidesOCTOBER 11, 2017, New publication from the Khvorova lab. Pharmacokinetic Profiling of Conjugated Therapeutic Oligonucleotides: A High-Throughput Method Based Upon Serial Blood Microsampling Coupled to Peptide Nucleic Acid Hybridization Assay. Godinho BMDC, Gilbert JW, Haraszti RA, Coles AH, Biscans A, Roux L, Nikan M, Echeverria D, Hassler M, Khvorova A. Nucleic Acid Ther. 2017 Oct 12. doi: 10.1089/nat.2017.0690. 

Li Weibo Institute for Rare Disease ResearchOCTOBER 11, 2017, UMass Medical School announces The Li Weibo (李伟波) Institute for Rare Diseases Research: $10 million endowment gift from Li Weibo Charitable Foundation to support world-leading research at UMMS. Learn more here.


18s rRNA ribosomal decay non-functionalSEPTEMBER 27, 2017, New publication from the Moore lab. 
ASC1 and RPS3: New actors in 18S nonfunctional rRNA decay. Limoncelli KA, Merrikh CN, Moore MJ. RNA. 2017 Sep 27. pii: rna.061671.117. doi: 10.1261/rna.061671.117.

Alterations in mRNA 3′ UTR Isoform Abundance Accompany Gene Expression Changes in Human Huntington’s Disease BrainsSEPTEMBER 26, 2017, New publication from the Aronin lab. Alterations in mRNA 3' UTR Isoform Abundance Accompany Gene Expression Changes in Human Huntington's Disease Brains.  Romo L, Ashar-Patel A, Pfister E, Aronin N. Cell Rep. 2017 Sep 26;20(13):3057-3070. doi: 10.1016/j.celrep.2017.09.009

Diatrack particle tracking softwareSEPTEMBER 25, 2017, New publication from the Grunwald lab. Diatrack particle tracking software: a review of applications and performance evaluation. Vallotton P, van Oijen AM, Whitchurch CB, Gelfand V, Yeo L, Tsiavaliaris G, Heinrich S, Dultz E, Weis K, and Grunwald D. Traffic. Accepted manuscript online: 25 SEP 2017 DOI: 10.1111/tra.12530

Transcriptome wide Poly Adenylation sites preeclampsiaSEPTEMBER 25, 2017, New publication from the Moore lab. FLT1 and transcriptome-wide polyadenylation site (PAS) analysis in preeclampsia. Ashar-Patel A, Kaymaz Y, Rajakumar A, Bailey JA, Karumanchi SA, Moore MJ. Sci Rep. 2017 Sep 22;7(1):12139. doi: 10.1038/s41598-017-11639-6.

Oligonucleotide Therapeutics Society Craig Mello Jonathan WattsSEPTEMBER 24, 2017 Craig Mello presented a keynote address, 'A Worms Tale: Oligonucleotide-Guided Gene Regulation and Secrets of Inheritance and Immortality', at the 13th Annual Oligotherapeutics Society meeting. Jonathan Watts presented his work on 'Modification and Multimerization of Therapeutic Oligonucleotides'. Annabelle Biscans, Khvorova lab, was selected by the committee to give an oral presentation; Socheata Ly, Khvorova lab & Alexandre Debacker, Watts lab, both were awarded travel grants.

Li-Chun Tu David Grunwald SEPTEMBER 15, 2017 Congratulations, Li-Chun Tu, recipient of an NIH K99 grant award 'Deciphering real-time dynamics of the human genome organization in response to DNA damage and gene expression'! This proposal describes an approach that allows chromosome dynamics to be directly visualized, tracked, and characterized at high resolution in live cells. Understanding the dynamics and mechanisms of chromosome rearrangements in response to DNA damage and transcriptional activation will significantly improve our understanding of human genome stability and nuclear function.

Locked Nucleic Acid Gapmers and Conjugates Potently Silence ADAM33, an Asthma-Associated Metalloprotease with Nuclear-Localized mRNASEPTEMBER 15, 2017, New publication from the Watts lab. Locked Nucleic Acid Gapmers and Conjugates Potently Silence ADAM33, an asthma-associated Metalloprotease with Nuclear-Localized mRNA. Pendergraff HM, Krishnamurthy PM, Debacker AJ, Moazami MP, Sharma VK, Niitsoo L, Yu Y, Tan YN, Haitchi HM, Watts JK. Mol Ther Nucleic Acids. 2017 Sep 15.

Andrei Korostelev Lab RibosomeSEPTEMBER 12, 2017 Congratulations to Andrei Korostelev, recipient of the Earl & Thressa Stadtman Scholar Award! Dr. Korostelev will be awarded this honor and present a lecture at the annual American Society for Biochemistry & Molecular Biology meeting in April in San Diego, CA, USA. Learn more here.

Rhino gives voice to silent chromatinSEPTEMBER 7, 2017 Nature News & Views article written by Dr. Phillip Zamore, "Molecular biology: Rhino gives voice to silent chromatin" Nature 549, 38–39. 07 September 2017.

 The genome of Trichoplusia ni, an agricultural pest and novel model for small RNA biologySEPTEMBER 4, 2017, New publication from the Zamore lab. The genome of Trichoplusia ni, an agricultural pest and novel model for small RNA biology. Fu Y, Yang Y, Zhang H, Farley G, Wang J, Quarles KA, Weng Z, Zamore PD. BioRxiv, posted Sept 4.

Loading of Extracellular Vesicles with Chemically Stabilized Hydrophobic siRNAs for the Treatment of Disease in the Central Nervous System.

SEPTEMBER 1, 2017, New publications from the Khvorova lab:
Loading of Extracellular Vesicles with Chemically Stabilized Hydrophobic siRNAs for the Treatment of Disease in the Central Nervous System. Haraszti RA, Coles A, Aronin N, Khvorova A, Didiot MC. Bio Protoc. 2017 Aug 20;7(16)

A High-throughput Assay for mRNA Silencing in Primary Cortical Neurons in vitro with Oligonucleotide Therapeutics   A High-throughput Assay for mRNA Silencing in Primary Cortical Neurons in vitro with Oligonucleotide Therapeutics  Alterman JF, Coles A, Hall LM, Aronin N, Khvorova A, Didiot MC. Bio Protoc. 2017 Jun 20;7(12). 

 

Jonathan WattsSEPTEMBER 1, 2017 Congratulations to Jonathan Watts, the first recipient of the Ono Pharma Breakthrough Science Initiative Award! Awards of $300,000/year for oligonucleotide medicine research, possibly renewable, totaling a maximum of $900,000 for the normal term of a research project in oligonucleotide research.

Oligonucleotide Therapeutics Society Craig Mello Jonathan WattsAUGUST 29, 2017 Congratulations to Socheata Ly, Khvorova Lab and Alexandre Debacker, Watts Lab for receiving travel awards to the Oligonucleotide Therapeutics Society meeting in Bordeaux, France, September 24-27. Congratulations to Annabelle Biscans for being selected to present a short talk at this meeting. RTI Faculty Jonathan Watts and Craig Mello were invited to present talks, Craig Mello will be keynoting this conference.

anti-CRISPR

AUGUST 23, 2017, New publication from the Sontheimer lab. A Broad-Spectrum Inhibitor of CRISPR-Cas9. Harrington LB, Doxzen KW, Ma E, Liu JJ, Knott GJ, Edraki A, Garcia B, Amrani N, Chen JS, Cofsky JC, Kranzusch PJ, Sontheimer EJ, Davidson AR, Maxwell KL, Doudna JA.Cell. 2017 Aug 23. pii: S0092-8674(17)30873-5. doi: 10.1016/j.cell.2017.07.037. [Epub ahead of print]

Mouse cerebellumAUGUST 23, 2017 RTI Gallery of images LIVE as a Cell Picture Show, hosted by the publisher of the journal CellTo look at all of the images in this gallery, click here. For more information, see this link to our UMassMedNow article here.

Anastasia Khvorova

AUGUST 16, 2017 U.S. Rep. Jim McGovern meets with Anastasia Khvorova, Chancellor Michael    Collins, Dean Terry Flotte, Beth   McCormick and others to discuss critical NIH funding for UMass   Medical School. Video of the discussion can be found here. Link to the article in the Worcester Telegram & Gazette here.

antiCRISPRs

JUNE 29, 2017, New publication from the Sontheimer lab. Inhibition of CRISPR-Cas systems by mobile genetic elements. Sontheimer EJ, Davidson AR. Curr Opin Microbiol. 2017 Jun 29;37:120-127. doi: 10.1016/j.mib.2017.06.003. [Epub ahead of print] Review.

Exon SkippingJUNE 14, 2017, New publication from the Xue, Sontheimer, & Moore labs. CRISPR/Cas9-mediated genome editing induces exon skipping by alternative splicing or exon deletion. Mou H†, Smith JL†, Peng L, Yin H, Moore J, Zhang XO, Song CQ, Sheel A, Wu Q, Ozata DM, Yingxiang Li Y, Anderson DG, Emerson CP, Sontheimer EJ, Moore MJ, Weng Z, Xue W. Genome Biology 2017 18:108 DOI: 10.1186/s13059-017-1237-8  Editorial hihlighting this publication can be found here.

hsiRNA structureJUNE 12, 2017, New publication from the Khvorova lab. 5-Vinylphosphonate improves tissue accumulation and efficacy of conjugated siRNAs in vivo. Haraszti RA, Roux L, Coles AH, Turanov AA, Alterman JF, Echeverria D, Godinho BMDC, Aronin N, Khvorova A. Nucleic Acids Res. 2017 Jun 7. doi: 10.1093/nar/gkx507. [Epub ahead of print] PMID: 28591791

Jonathan Watts, PhDJUNE 7, 2017 Worcester Foundation Research Grant recipients awarded to three faculty members in the RTI: 
David Grünwald, Ph.D.“Prototype development for a 20 color, 3D real-time microscope”
Andrei Korostelev, Ph.D., “Elucidating the translation-transcription coupling”
Jonathan Watts, Ph.D., “T to C conversion for amplifiable metabolic labeling of DNA at single base resolution”

Andrei Korostelev, PhDMAY 24, 2017, New publication from the Korostelev lab. “Transfer RNAs & the ribosome decoding centers that read their genetic instructions are almost the same for all life on earth—that’s why we are very excited by this discovery, which explains the accuracy of genetic code reading,” -Dr. Korostelev   Ensemble cryo-EM elucidates the mechanism of translation fidelity. Loveland AB, Demo G, Grigorieff N, & Korostelev AA. Nature (2017) doi:10.1038/nature22397  For details, please click here

Melissa Moore, PhD

MAY 2, 2017 Melissa Moore, Ph.D., Eleanor Eustis Farrington Chair in Cancer Research and Professor in the RNA Therapeutics Institute has been newly elected to the National Academy of Sciences. Dr. Moore, who was appointed a chief scientific officer of the messenger RNA platform at Moderna Therapeutics last fall, was among 84 new members and 21 foreign associates elected, in recognition of their distinguished and continuing achievements in original research. For details, please click here.

Mouse brain sectionMAY 2, 2017, New publication from the Khvorova & Aronin labs. Synthesis and Evaluation of Parenchymal Retention and Efficacy of a Metabolically Stable, O-phosphocholine-N-docosahexaenoyl-L-serine siRNA Conjugate in Mouse Brain. Nikan M, Osborn MF, Coles AH, Biscans A, Godinho B, Haraszti R, Sapp E, Echeverria D, DiFiglia M, Aronin N, and Khvorova A. Just Accepted Manuscript. Bioconjugate Chem, doi: 10.1021/acs.bioconjchem.7b00226

Ami Ashar-PatelAPRIL 21, 2017 Ami Ashar-Patel, a PhD candidate in the Moore lab, has been selected to participate in the Keck Graduate Institute (KGI) Certificate in Bioscience Management Program. She received a KGI Burroughs Wellcome Fund scholarship and a UMass Medical School Graduate School of Biomedical Sciences career development grant. For details, please click here.

Structure and dimer formation of RlmH.

APRIL 20, 2017, New publication from the Korostelev & Zamore labs. Small methyltransferase RlmH assembles a composite active site to methylate a ribosomal pseudouridine Koh CS, Madireddy R, Beane TJ, Zamore PD, & Korostelev AA. Scientific Reports 7, Article number: 969 (2017) doi:10.1038/s41598-017-01186-5 PMID: 28428565 

Neil AroninAPRIL 12, 2017 Neil Aronin, MD, Professor of Medicine & RNA Therapeutics Institute, co-director of the Neurotherapeutics Institute, chief of the division of endocrinology & metabolism will serve as the Higgins Family Professor of Neuroscience. A member of the UMMS faculty since 1981, Dr. Aronin established and has maintained groundbreaking research focused on Huntington’s disease; and recent explorations of how gene therapy might be used to slow the progression may lead to promising clinical trials.

APRIL 10, 2017 Andrei Korostelev, Ph.D., Associate Professor of RNA Therapeutics Institute, was in the Worcester Telegram & Gazette this past Saturday.  Andrei discussed how the new Cryo-EM at UMASS Medical School helps his lab study the movement and function of the ribosome, the most important cellular machine for making proteins. For details, please click here.

APRIL 4, 2017, New publication from the Korostelev lab. “This is an important paper that describes an alternate rescue system in bacteria for ribosomes that are stalled on an mRNA without a stop codon.” by a reviewer. Mechanism of ribosome rescue by ArfA and RF2. Demo G, Svidritskiy E, Madireddy R, Diaz-Avalos R, Grant T, Grigorieff N, Sousa D, Korostelev AA.  Elife. 2017 Mar 16;6. pii: e23687. doi: 10.7554/eLife.23687. PMID: 28300532.

MARCH 20, 2017, New publication from the Mello lab. The Antiviral RNA Interference Response Provides Resistance to Lethal Arbovirus Infection and Vertical Transmission in Caenorhabditis elegans.  Gammon DB, Ishidate T, Li L, Gu W, Silverman N, Mello CC.  Curr Biol. 2017 Mar 20;27(6):795-806. doi: 10.1016/j.cub.2017.02.004. Epub 2017 Mar 2. PMID: 28262484

FEBRUARY 15, 2017  Dr. Erik J. Sontheimer, a professor in the RNA Therapeutics Institute, is quoted in Science in a story about the patent battle over CRISPR/Cas9 technology.  For details, please click here.

FEBRUARY 13, 2017  Wen Xue, Ph.D., Assistant Professor of RTI, is in The Boston Globe talking about promising Immunotherapy fighting lung cancer. For details, please click here.

FEBRUARY 1, 2017  Phillip D. Zamore, Ph.D., co-director of the RNA Therapeutics Institute is in The Scientist to talk about RNA interference between plant and pathogen. For details, please click here.

Anastasia KhvorovaJANUARY 6, 2017  Anastasia Khvorova, Ph.D., professor of RNA Therapeutics Institute, explains the promise of oligonucleotide therapeutics, including the results of Phase I clinical trial of a new injectable cholesterol-lowering drug Inclisiran in NEJM. Inclusion is a chemically modified siRNA developed by Alnylam Pharmaceuticals, a company co-founded by Phillip Zamore, Ph.D., Howard Hughes Medical Institute Investigator, the Gretchen Stone Cook Chair of Biomedical Sciences & Director of the RTI. For details, please click here.

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