DOCSLIB.ORG

David M. Garcia, Phd Education and Training Pre-Prints Research

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
David M. Garcia, Phd Education and Training Pre-Prints Research David M. Garcia, PhD Assistant Professor University of Oregon Department of Biology, Institute of Molecular Biology, Center for Genome Function [email protected] https://www.garcialab.org/ Education and Training Stanford University School of Medicine, Department of Chemical and Systems Biology, Stanford, CA Ford Foundation/NIH NRSA/Burroughs Wellcome Fund Postdoctoral Fellow, 2013—2018 Advisor: Daniel Jarosz Massachusetts Institute of Technology, Department of Biology, Cambridge, MA Ph.D. Molecular Biology, 2006—2012 Advisor: David Bartel University of California, Santa Cruz B.S. Biochemistry and Molecular Biology, with College Honors, 1998—2002 Pontificia Universidad Católica de Chile, Santiago, Chile, 2003 (study abroad) Pre-prints Garcia, D.M.*, ‡, Campbell, E.A.*, Jakobson, C.M., Tsuchiya, M., DiNardo, A.L., Kaeberlein, M., Jarosz, D.F. ‡ A prion accelerates proliferation at the expense of lifespan. bioRxiv (Under review) https://doi.org/10.1101/2020.07.10.196584 Byers, J.S., Garcia, D.M., Jarosz, D.F. Epigenetic regulation of genome integrity by a prion-based mechanism. bioRxiv (Under revision) https://doi.org/10.1101/152512 *equal contributions ‡co-corresponding authors Research Publications Chakravarty, A.K., Smejkal, T., Itakura, A., Garcia, D.M., Jarosz, D.F. A non-amyloid prion particle that activates a heritable gene expression program. Molecular Cell ePub: Nov. 19, 2019 • Preview: Yeast Sporulation and [SMAUG+] Prion: Faster is Not Always Better, Molecular Cell 2019, 77(2) Garcia, D.M.*, Dietrich, D.*, Clardy, J.‡, Jarosz, D.F.‡ A common bacterial metabolite elicits prion- based bypass of glucose repression. eLife 2016, 5:e17978 • eLife Insight: An acid tale of prion formation. Tuite, M.F., eLife 2016, 5:e22256 • Editor’s Choice: Bacteria stop fermentation with lactic acid. Science Signaling 9,457:ec288 • Stanford Medicine Scope: How prions help yeast feast. Spector, R., December 1, 2016 1 Chakrabortee, S.*, Byers, J.S.*, Jones, S., Garcia, D.M., Bhullar, B., Chang, A., She, R., Lee, L., Fremin, B., Lindquist, S. ‡, Jarosz, D.F. ‡ Intrinsically Disordered Proteins Drive Emergence and Inheritance of Biological Traits. Cell 167, 369–381, 2016 • Remembering the Past: A New Form of Protein-Based Inheritance. Tuite, M.F., Cell 167, 369–381, 2016 • Science Daily: Revising the meaning of ‘prion’. October 4, 2016 • Stanford Medicine Scope: DNA dethroned? Spector, R., October 6, 2016 Garcia, D.M. and Jarosz D.F. Rebels with a cause: molecular features and physiological consequences of yeast prions. (Review) FEMS Yeast Research 14 (1): 136–147, 2014 Garcia, D.M.*, Baek, D.*, Shin, C., Bell, G.W., Grimson, A., Bartel, D.P. Weak Seed-Pairing Stability and High Target-Site Abundance Decrease the Proficiency of lsy-6 and Other miRNAs. Nature Structural and Molecular Biology, 18 (10): 1139–1146, 2011 *equal contributions ‡co-corresponding authors Research Mentoring Ethan Shaw, PhD student, June 2019—present Stanley and Lucille Adamson Award (2019) Abigail Vaaler, Research Assistant/Lab Manager, July 2019—present Zack Basham, undergraduate, January 2019–June 2020; Research Assistant, July 2020—present UO SPUR/OURS Summer Fellowship (2019) Mikala Capage, undergraduate, February 2019–present UO VPRI Undergraduate Fellowship (2020) Jacob Evarts, undergraduate, March 2019–present UO VPRI Undergraduate Fellowship (2019) UO SPUR/OURS Summer Fellowship (2020) Rotation PhD students: Natanya Villegas (W2020); Acadia DiNardo (F2019); Zac Bush (S2019) Grants as independent investigator Donald E. and Delia B. Baxter Foundation, $100k, 6/2020–5/2021 Medical Research Foundation of Oregon New Investigator Grant, $40k, 9/2019–8/2020 University of Washington Nathan Shock Center Pilot Award, $10k, 9/2019–8/2020 Service as faculty member Diversity, Equity and Inclusion Committee, Department of Biology, 2019–present Founder, Oregon RNA Club. Awarded mini-grant from RNA Society to support club activities. 2 Center for Genome Function. Awarded mini-grant from UO CAS for hosting Symposium in ‘20–‘21. Ad-hoc reviewer: Frontiers in Microbiology (2020) Teaching as faculty member (forthcoming) Molecular Genetics, Bi 320 – first assignment is Spring 2021 (proposed) Systems Genetics, Bi ??? – first assignment in 2021–2022 year Scientific Teaching Fellow, Summer Institute on Scientific Teaching, Yale Poorvu Center for Teaching and Learning, Regional 4-day Workshop, summer 2019 Oral Presentations (selected) Yeast Genetics Meeting (Genetics Society of America), 2018 Poster Presentations (selected) Cold Spring Harbor Labs Yeast Research: Origins, Insights, Breakthroughs, New York, 2019 Cold Spring Harbor Labs 84th Symposium: RNA Control and Regulation, New York, 2019 Memberships Genetics Society of America (ID#: 362026), 2018–present RNA Society (#1322085), 2019–present ORCiD iD: 0000-0003-0600-9527 Websites https://www.garcialab.org/ https://scholar.google.com/citations?user=svSKbSIAAAAJ&hl=en linkedin.com/in/david-m-garcia-76737a54 Twitter handle: @UdPrfrNAgo NCBI MyBibliography: https://www.ncbi.nlm.nih.gov/sites/myncbi/1zArUNKdFMyAI/bibliography/53457122/pu blic/?sort=date&direction=ascending 3 Pre-faculty training Postdoctoral Fellow Grants and Fellowships Burroughs Wellcome Fund Postdoctoral Enrichment Program Award, $60K, 2015—2018 Stanford Medicine SPARK Grant (PI w/ 7 co-investigators), $100K, 2015—2017 NIH Ruth L. Kirschstein National Research Service Award, NIGMS, $112K, 2014—2016 Ford Foundation Postdoctoral Fellowship, National Academy of Sciences, $42.5K, 2013—2014 Awards and Honors during training Kavli Frontiers of Science Fellow, National Academy of Sciences, 2015 Poster Award, Gordon Research Conference: Epigenetics, 2015 Poster Award, Stanford Chemical and Systems Biology Retreat, 2015 MIT S. Klein Prize for Science Writing, First Place, 2012 Phi Beta Kappa, 2004 UC Santa Cruz Alumni Association Scholarship, 2001 Patents “Use of a Small Molecule to Robustly Alter the Metabolic Program of Fungi” (US Provisional) 2016 Garcia, D.M., Dietrich, D., Clardy, J., Jarosz, D.F. Science writing for the public Garcia, D.M. Extreme Tissue Regeneration. OZY magazine, 2014 ozy.com/fast-forward/need-a-new-heart-make-like-a-worm-grow-your-own/30298 Garcia, D.M. Great Adaptations: A versatile bacterium provides insight into multicellular microbial life and tackling deadly infections. Natural History Magazine, 2012 naturalhistorymag.com/perspectives/212397/great-adaptations Garcia, D.M. You’d Prefer An Argonaute, a blog about RNA research and biomedical science. >50,000 views. youdpreferanargonaute.com Oral Presentations (seminars, symposia, conferences, etc.) Third Rock Ventures, San Francisco, 2018 Stanford Department of Biology Think & Drink, 2017 Nuclear Dynamics Seminar Series, Institut Curie, Paris, France, 2017 Bay Area Stress & Chaperone Symposium, UC Berkeley, 2017 Stanford Microbial Molecular Biology Seminar Series, 2017 4 Stanford Microbial Molecular Biology Seminar Series, 2015 Stanford Department of Chemical and Systems Biology Retreat, 2015 Ford Fellows Conference, National Academy of Sciences, Washington D.C., 2013 Stanford Department of Chemical and Systems Biology Retreat, 2013 Stanford Department of Developmental Biology Retreat, 2013 5th Small RNA Microsymposium, Institute of Molecular Biotechnology, Vienna, Austria, 2010 UC San Francisco Hematopoiesis and Leukemia Super-Group Meeting, 2006 Oral Presentations (faculty candidate talks) NYU School of Medicine, Department of Biochemistry and Molecular Pharmacology, 2018 University of Oregon, Institute of Molecular Biology, 2018 The Hospital for Sick Children Research Institute/University of Toronto, 2018 Sloan Kettering Institute, Molecular Biology Program, 2018 University of Chicago, Department of Molecular Genetics and Cell Biology, 2018 University of Michigan, Ann Arbor, Life Sciences Institute, 2018 University of Colorado, Boulder, Department of Chemistry and Biochemistry, 2018 UC Santa Barbara, Department of Molecular, Cellular and Developmental Biology, 2018 Max F. Perutz Laboratories (MFPL), Vienna, Austria, 2018 Case Western Reserve University School of Medicine, Ctr. for RNA Science and Therapeutics, 2017 Poster Presentations (selected) 3rd Stanford Microbiome Symposium, Stanford, CA, 2017 1st Symposium on Nucleic Acid Modifications, IMB, Mainz, Germany, 2017 Bay Area Stress & Chaperone Symposium, UC Berkeley, Berkeley, CA, 2017 EMBO Conference: Experimental Approaches to Evolution and Ecology using Yeast and other Model Systems, EMBL ATC, Heidelberg, Germany, 2016 EMBO Practical Course: iCLIP, Institute of Molecular Biology, Mainz, Germany, 2015 Burroughs Wellcome Fund New Awardees Networking Meeting, Research Triangle Park, NC, 2015 Stanford University School of Medicine, Department of Chemical and Systems Biology Annual Retreat, Santa Cruz, CA, 2015 Joan Mansour Poster Award Sixth Indo-American Kavli Frontiers of Science Symposium, Beckman Center of the National Academies of Sciences and Engineering, Irvine, CA, 2015 Invited presenter 5 Gordon Research Conference: Epigenetics, Waltham, MA, 2015 Poster Award (1 of 4 awardees out of 133 posters) EMBO Workshop: Macromolecular Assemblies at the Crossroads of Cell Stress and Function, The Hebrew University, Jerusalem, Israel, 2015 EMBO Symposia: The Non-Coding Genome, EMBL ATC, Heidelberg, Germany, 2010 Keystone Symposium: RNAi, microRNA, and non-coding RNA, Victoria, Canada, 2009 Teaching during prior training Postdoc Mentor, Stanford Biosciences ADVANCE Summer Institute (URM PhD students) 2016, 2017. TA, MIT Biology, Experimental
Load more

Recommended publications
  • 2008-Annual-Report.Pdf
    whitehead institute 2008 AnnuAl RepoRt. a year in the life of a scientific community empowered to explore biology’s most fundamental questions for the betterment of human health. whitehead institute 2008 annual report a Preserving the mission, contents facing the future 1 preserving the mission, it’s customary in this space to recount and reflect facing the future on the accomplishments of the year gone by. i’ll certainly do so here—proudly—but in many 5 scientific achievement important ways, 2008 was about positioning the institute for years to come. 15 principal investigators many colleges, universities, and independent 30 whitehead fellows research institutions found themselves in dire fiscal positions at the close of 2008 and entered 34 community evolution 2009 in operational crisis reflective of the global economic environment. hiring freezes and large- 40 honor roll of donors scale workforce reductions have become the norm. although whitehead institute is certainly not 46 financial summary insulated from the impact of the downturn, i am 48 leadership pleased and somewhat humbled to report that the institute remains financially strong and no less 49 sited for science committed to scientific excellence. david page, director over the past two years, we have been engaged in a focused effort to increase efficiency and editor & direCtor reduce our administrative costs, with the explicit goal of ensuring that as much of the institute’s matt fearer revenue as possible directly supports Whitehead research. Our approach, which has resulted in assoCiate editor nicole giese a 10-percent reduction in operational expense, has been carefully considered. every decision offiCe of CommuniCation and PubliC affairs has been evaluated not just for its potential effects on our scientific mission, but also for 617.258.5183 www.whitehead.mit.edu possible consequences to the whitehead community and its unique culture.
    [Show full text]
  • Dr. David P. Bartel Journal Interviews
    Home About Scientific Press Room Contact Us ● ScienceWatch Home ● Interviews Featured Interviews Author Commentaries Institutional Interviews 2008 : June 2008 - Author Commentaries : Dr. David P. Bartel Journal Interviews Podcasts AUTHOR COMMENTARIES - 2008 ● Analyses June 2008 Featured Analyses Dr. David P. Bartel A Featured Scientist from Essential Science IndicatorsSM What's Hot In... Special Topics Earlier this year, ScienceWatch.com published an analysis of high-impact research in Molecular Biology & Genetics over the past five years. The ● Data & Rankings analysis ranked David Bartel #2 among authors publishing high-impact papers in this field, based on 19 papers cited a total of 4,542 times. Sci-Bytes In Essential Science Indicators from Thomson Reuters, Dr. Bartel's record Fast Breaking Papers includes 76 original articles and review papers published between January 1, New Hot Papers 1998 and February 29, 2008, with a total of 10,386 cites. These papers can be found in the fields of Molecular Biology & Genetics, Biology & Emerging Research Fronts Biochemistry, and Plant & Animal Science. Fast Moving Fronts Research Front Maps Current Classics Dr. Bartel is a Howard Hughes Medical Institute investigator whose lab is based at the Whitehead Institute Top Topics for Biomedical Research in Cambridge, Massachusetts. He is also a Professor in the Department of Biology at MIT. Rising Stars New Entrants In the interview below, he talks with correspondent Gary Taubes about his highly cited research. Country Profiles What motivated your research originally on these small, non-coding RNAs, and particularly the 2000 Cell paper (Zamore PD, et al., RNAi: double-stranded RNA directs the ATP-dependent ● About Science Watch cleavage of mRNA at 21 to 23 nucleotide intervals," 101[1]: 25-33, 31 March 200), which is your most-highly cited paper that’s not a review? Methodology Tom Tuschl and Phil Zamore [see also] were postdocs in my lab working in collaboration with Phil Sharp Archives [see also] on the biochemistry of RNAi.
    [Show full text]
  • Fire Departments of Pathology and Genetics, Stanford University School of Medicine, 300 Pasteur Drive, Room L235, Stanford, CA 94305-5324, USA
    GENE SILENCING BY DOUBLE STRANDED RNA Nobel Lecture, December 8, 2006 by Andrew Z. Fire Departments of Pathology and Genetics, Stanford University School of Medicine, 300 Pasteur Drive, Room L235, Stanford, CA 94305-5324, USA. I would like to thank the Nobel Assembly of the Karolinska Institutet for the opportunity to describe some recent work on RNA-triggered gene silencing. First a few disclaimers, however. Telling the full story of gene silencing would be a mammoth enterprise that would take me many years to write and would take you well into the night to read. So we’ll need to abbreviate the story more than a little. Second (and as you will see) we are only in the dawn of our knowledge; so consider the following to be primer... the best we could do as of December 8th, 2006. And third, please understand that the story that I am telling represents the work of several generations of biologists, chemists, and many shades in between. I’m pleased and proud that work from my labo- ratory has contributed to the field, and that this has led to my being chosen as one of the messengers to relay the story in this forum. At the same time, I hope that there will be no confusion of equating our modest contributions with those of the much grander RNAi enterprise. DOUBLE STRANDED RNA AS A BIOLOGICAL ALARM SIGNAL These disclaimers in hand, the story can now start with a biography of the first main character. Double stranded RNA is probably as old (or almost as old) as life on earth.
    [Show full text]
  • Whitehead Faculty and Fellows Members
    Whitehead Faculty and Fellows Members Ask a visiting scientist to describe Whitehead Institute and three themes David Bartel studies microRNAs and other small RNAs emerge immediately: the exceptional quality of the scientific staff, the that specify the destruction and/or translational collaborative spirit, and the ethos that encourages researchers at every level repression of mRNAs. He also studies mRNAs, focusing to share new ideas and benefit from the insights and experience of their on their untranslated regions and poly(A) tails, and colleagues. how these regions recruit and mediate regulatory processes. His lab found that microRNAs affect most human protein-coding genes, either by regulating The key to this combination of excellence and accessibility is, of course, the them or by shaping their evolution. Faculty. “From the beginning, we sought researchers who had terrific scientific instincts, but we were also looking for people who would feel comfortable in Iain Cheeseman investigates the process of our open environment,” says Founding Member Gerald Fink. “The exchange chromosome segregation and cell division. In of energy and new ideas never stops, from the formal research retreat, to the particular, he uses proteomics, biochemistry, cell faculty lunches, to the countless informal conversations in hallways and biology, and functional approaches to examine the lounges.” composition, structure, organization and function of the kinetochore — the group of proteins that assemble Whitehead Institute faculty, known as Members, are selected through a joint at the centromere and are required for chromosome appointment process with the Massachusetts Institute of Technology (MIT) segregation and cell division. Department of Biology. Whitehead Institute is solely responsible for their salary and research.
    [Show full text]
  • Micrornas Generate Gene Expression Thresholds with Ultrasensitive Transitions
    MicroRNAs generate gene expression thresholds with ultrasensitive transitions Shankar Mukherji1,*, Margaret S. Ebert2,3,*, Grace X. Zheng2,4, John S. Tsang5, Phillip A. Sharp2,3, and Alexander van Oudenaarden2,6,# dramatically. In particular, we show that regulation by Short Abstract — MicroRNAs are an abundant class of post- miRNAs establishes a threshold level of target mRNA below transcriptional regulator whose repressive effects are thought which protein production is highly repressed. Beyond this to have broad reach in terms of number of targets but modest threshold, there is a regime in which expression responds effect for any given target. In this study we performed a single- cell analysis of the effects of microRNA-mediated repression. ultrasensitively to target mRNA input until reaching high We observe that microRNAs generate gene expression enough mRNA levels to almost escape repression by thresholds by which target protein production is robustly miRNA. We constructed a mathematical model, similar to silenced below a given transcriptional activity and is activated models used to describe small RNA (sRNA) reguation in in an ultrasensitive fashion as the transcriptional activity is bacteria [7] and protein-protein titration effects [8,9], increased. The threshold can be tuned by modulating the describing repression of target gene expression by both non- microRNA concentration and the number of microRNA binding sites in the target 3’-UTR. catalytic and catalytic activity of miRNA. The model predicted, and experiments confirmed, that the ultrasensitive Keywords — microRNA, gene expression, post- regime could be shifted to higher target mRNA levels by transcriptional regulation transfecting additional miRNA or by increasing the number of miRNA binding sites in the 3’ UTR of the target mRNA.
    [Show full text]
  • Signature of Author
    Computational and experimental analysis of plant microRNAs by Matthew W. Jones-Rhoades B.A., Chemistry (1999) Grinnell College Submitted to the Department of Biology in Partial Fulfillment of the Requirement for the Degree of Doctor of Philosophy in Biology MASSACHUSETTSINSTATE at the OF TECHNOLOGY Massachusetts Institute of Technology MAY 2 7 2005 June 2005 LIBRARIES © 2005 Massachusetts Institute of Technology All rights reserved Signatureof Author.................................... ................. ................. Department of Biology x.. '"---.~ May 20, 2005 Certified by ......... · .................................................... David P. Bartel Professor of Biology Thesis Supervisor Acceptedby ... ......... Stephen P. Bell Professor of Biology Chairman, Graduate Student Committee ,' tti v ;S Computational and experimental analysis of plant microRNAs Matthew W. Jones-Rhoades Submitted to the Department of Biology on May 20, 2005 in Partial Fulfillment of the Requirement for the Degree of Doctor of Philosophy in Biology ABSTRACT MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs that mediate gene regulation in plants and animals. We demonstrated that Arabidopsis thaliana miRNAs are highly complementary (0-3 mispairs in an ungapped alignment) to more mRNAs than would be expected by chance. These mRNAs are therefore putative regulatory targets of their complementary miRNAs. Many miRNA complementary sites are conserved to the monocot Oryza sativa (rice), implying evolutionary conservation based on function at the nucleotide level. The majority of predicted miRNA targets encode for transcription factors and other proteins with known or inferred roles in developmental patterning, implying that the miRNAs themselves are high-level regulators of development. Our findings indicated that miRNAs are key components of numerous regulatory circuits in plants and set the stage for numerous additional experiments to investigate in depth the significance of miRNA-mediated regulation for particular target families and genes.
    [Show full text]
  • Springer A++ Viewer
    PublisherInfo PublisherName : BioMed Central PublisherLocation : London PublisherImprintName : BioMed Central Primate-specific microRNAs found ArticleInfo ArticleID : 5096 ArticleDOI : 10.1186/gb-spotlight-20050620-01 ArticleCitationID : spotlight-20050620-01 ArticleSequenceNumber : 72 ArticleCategory : Research news ArticleFirstPage : 1 ArticleLastPage : 4 RegistrationDate : 2005–6–20 ArticleHistory : OnlineDate : 2005–6–20 ArticleCopyright : BioMed Central Ltd2005 ArticleGrants : ArticleContext : 130596611 Charles Q Choi Email: [email protected] Israeli scientists have identified what may be the first microRNAs specific to primates, in research published online June 19 in Nature Genetics. They suggest these new microRNAs might mean that hundreds remain to be found in the human genome. "Finding a group of genes that is specific to primates is very important for understanding our evolution, and bears significant diagnostic and therapeutic potential," lead researcher Isaac Bentwich, at Rosetta Genomics in Rehovot, told The Scientist. MicroRNAs are single-stranded RNAs roughly 22 nucleotides long that regulate gene expression by binding to target gene mRNAs. The DNA sequence that codes for a microRNA gene includes the microRNA sequence and a nearby complementary sequence that, when transcribed, form a double- stranded RNA hairpin loop. Past studies have identified 222 human microRNAs, of which scientists had confirmed the sequences of only 86 in humans. To uncover more, Bentwich and colleagues computationally folded the entire human genome into hairpins 55 nucleotides or longer. Of 11 million potential hairpins, 434,239 appeared to be viable microRNA candidates. "Conventional approaches start with genome comparisons, to identify sequences important enough to be conserved across species. This new approach doesn't start with genome alignments. This allows them to find microRNAs not conserved beyond primates," Victor Ambros of Dartmouth Medical School in Hanover, N.H., who did not participate in this study, told The Scientist.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,790,922 B2 Tuschl Et Al
    USOO8790922B2 (12) United States Patent (10) Patent No.: US 8,790,922 B2 Tuschl et al. (45) Date of Patent: *Jul. 29, 2014 (54) RNASEQUENCE-SPECIFIC MEDIATORS OF 5,576,208 A 11/1996 Monia et al. RNA INTERFERENCE 5,578,716 A 1 1/1996 Szyfetal. 5,580,859 A 12/1996 Felgner et al. 5,594,122 A 1/1997 Friesen (75) Inventors: Thomas Tuschl, Brooklyn, NY (US); 5,624,803 A 4/1997 Noonberg et al. Phillip D. Zamore, Northborough, MA 5,624,808 A 4/1997 Thompson et al. (US); Phillip A. Sharp, Newton, MA 5,670,633. A 9, 1997 Cook et al. 5,672,695 A 9, 1997 Eckstein et al. (US); David P. Bartel, Brookline, MA 5,674,683 A 10, 1997 KOO1 (US) 5,712.257 A 1/1998 Carter 5,719,271 A 2f1998 Cook et al. (73) Assignees: Max-Planck-Gesellschaft zur 5,770,580 A 6/1998 Ledley et al. Forderung der Wissenschaften E.V. 5,795,715 A 8, 1998 Livache et al. Munich (DE); Massachusetts Institute 5,801,154 A 9, 1998 Baracchini et al. 5,814,500 A 9, 1998 Dietz of Technology, Cambridge, MA (US); 5,898,031 A 4/1999 Crooke Whitehead Institute for Biomedical 5,908,779 A 6/1999 Carmichael et al. Research, Cambridge, MA (US); 5,919,722 A 7/1999 Verduijn et al. University of Massachusetts, Boston, 5,919,772 A 7/1999 Szyfetal. 5,972,704 A 10/1999 Draper et al. MA (US) 5.998,203 A 12/1999 Matulic-Adamic et al.
    [Show full text]
  • Biochemical Mechanism of RNA Interference in Higher Organisms: a Dissertation
    University of Massachusetts Medical School eScholarship@UMMS GSBS Dissertations and Theses Graduate School of Biomedical Sciences 2005-08-26 Biochemical Mechanism of RNA Interference in Higher Organisms: A Dissertation Dianne S. Schwarz University of Massachusetts Medical School Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/gsbs_diss Part of the Amino Acids, Peptides, and Proteins Commons, Animal Experimentation and Research Commons, Genetic Phenomena Commons, and the Nucleic Acids, Nucleotides, and Nucleosides Commons Repository Citation Schwarz DS. (2005). Biochemical Mechanism of RNA Interference in Higher Organisms: A Dissertation. GSBS Dissertations and Theses. https://doi.org/10.13028/bzkt-qt51. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/186 This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in GSBS Dissertations and Theses by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. A Dissertation Presented By DIANNE S. SCHWARZ Submitted to the Faculty of the University of Massachusetts Graduate School of Biomedical Sciences, Worcester In partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY August 26, 2005 Biochemistry and Molecular Pharmacology ii BIOCHEMICAL MECHANISM OF RNA INTERFERENCE IN HIGHER ORGANISMS A Dissertation Presented By DIANNE S. SCHWARZ Approved as to style and content by: C. Robert Matthews, Ph.D, Chair
    [Show full text]
  • Molecular Characterization of Animal Micrornas: Sequence, Expression, and Stability
    Molecular Characterization of Animal microRNAs: Sequence, Expression, and Stability. by Nelson C. Lau B.S. Biochemistry and Molecular Biology University at Albany, SUNY, 1999 SUBMITTED TO THE DEPARTMENT OF BIOLOGY IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY AT THE MASSACHUSETTS INSTITUTE OF TECHNOLOGY SEPTEMBER 2004 ( 2004 Nelson C. Lau. All Rights Reserved. The author hereby grants to MIT permission to reproduce and to distribute publicly paper and electronic copies of this thesis document in whole or in part. Signature of Author: Department of Biology (June 30, 2004) Certified by: / David P. Bartel Professor of Biology Thesis Supervisor Accepted by: qtenhin P Rfll' Professor of Biology Chair, Biology Graduate Committee MASSACHUSETTS INSiEUTE OF TECHNOLOGY JUL 0 1 2004 1 LIBRARIES ARCHIVES Molecular Characterization of Animal microRNAs: Sequence, Expression, and Stability. by Nelson C. Lau Submitted to the Department of Biology On June 30, 2004 in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy ABSTRACT Multicellular organisms possess natural gene-regulatory pathways that employ small RNAs to negatively regulate gene expression. In nematodes, the small temporal RNAs (stRNAs), lin-4 and let-7, negatively regulate genes important in specifying developmental timing. A gene- silencing pathway present in plants, fungi and animals called RNA interference, involves the conversion of long double-stranded RNA into short interfering RNAs, which can serve to negatively regulate endogenous genes or suppress the replication of viruses and transposons. To investigate how wide a role small RNAs play in regulating gene expression in animals, we developed a RNA cloning procedure and first applied it to the cloning of small RNAs from the nematode, Caenorhabditis elegans.
    [Show full text]
  • Discovering the First Microrna-Targeted Drug
    Published October 29, 2012 JCB: Feature Discovering the first microRNA-targeted drug Morten Lindow1,2 and Sakari Kauppinen2,3 1Department of Biology, The Bioinformatics Centre, University of Copenhagen, DK-2200 Copenhagen, Denmark 2Santaris Pharma, DK-2970 Hørsholm, Denmark 3Department of Health Science and Technology, Aalborg University Copenhagen, DK-2450 Copenhagen SV, Denmark MicroRNAs (miRNAs) are important post-transcriptional first human oncogenic miRNAs (Eis et al., 2005; He et al., 2005; regulators of nearly every biological process in the cell Costinean et al., 2006). Since then, 18,226 miRNAs have been an- notated in animals, plants, and viruses, including 1,921 miRNAs and play key roles in the pathogenesis of human disease. encoded in the human genome (Kozomara and Griffiths-Jones, As a result, there are many drug discovery programs 2011). Indeed, miRNAs are predicted to repress a large fraction that focus on developing miRNA-based therapeutics. The of all protein-coding genes and to participate in the regulation most advanced of these programs targets the liver- of almost every biological process in the cell (Kloosterman and Downloaded from expressed miRNA-122 using the locked nucleic acid Plasterk, 2006; Bushati and Cohen, 2007; Bartel, 2009; Friedman (LNA)–modified antisense oligonucleotide miravirsen. et al., 2009; Ambros, 2011). Moreover, recent work implies that miRNA dysregulation is frequently associated with the patho- Here, we describe the discovery of miravirsen, which is genesis of human diseases (Gottwein and Cullen, 2008; Ventura currently in phase 2 clinical trials for treatment of hepatitis and Jacks, 2009; Williams et al., 2009; Mendell and Olson, C virus (HCV) infection.
    [Show full text]
  • Xuebing Wu, Ph.D
    Xuebing Wu, Ph.D. 630 West 168th Street Phone: (617) 301-1637 PS10-401 Email: [email protected] New York, NY 10032 Web: wu-lab.net EMPLOYMENT 11/1/2018- Assistant Professor Departments of Medicine and Systems Biology Columbia University Irving Medical Center 2014-2018 Helen Hay Whitney Postdoctoral Fellow Whitehead Institute for Biomedical Research Advisor: David P. Bartel, Ph.D. Research: Widespread influence of RNA structures on mRNA processing and stability EDUCATION 2009-2014 Ph.D. in Computational and Systems Biology Massachusetts Institute of Technology (MIT) Advisor: Phillip A. Sharp, Ph.D. (co-advisor: Christopher B. Burge, Ph.D.) Thesis: Mechanism and function of pervasive noncoding transcription in mammalian genomes 2007-2009 M.S. in Control Science and Engineering (Area: Bioinformatics) Department of Automation, Tsinghua University, China Advisor: Rui Jiang, Ph.D. Thesis: Disease gene and pathway identification using network alignment approaches 2003-2007 B.S. in Control Science and Engineering Department of Automation, Tsinghua University, China Advisor: Shao Li, M.D. (co-advisor: Michael Q. Zhang, Ph.D.) Thesis: Network-based global inference of human disease genes PUBLICATIONS * co-first authors; # co-corresponding authors 1. Zhang C*, Konermann S*, Brideau NJ, Lotfy P, Wu X, Novick SJ, Strutzenberg T, Griffin PR, Hsu PD, Lyumkis D. Structural basis for the RNA-guided ribonuclease activity of CRISPR-Cas13d. Cell. 2018, 175:212-223 2. Tycko J, Barrera LA, Huston N, Friedland AE, Wu X, Gootenberg JS, Abudayyeh OO, Myer VE, Wilson CJ, Hsu PD. Pairwise library screen systematically interrogates Staphylococcus aureus Cas9 specificity in human cells. Nature Communications. 2018, 9:2962 3.
    [Show full text]