Research Topics
Genomes and Genes | Derek M DykxhoornSummaryAffiliation: Harvard University Country: USA Publications
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Publications
Running interference: prospects and obstacles to using small interfering RNAs as small molecule drugsDerek M Dykxhoorn
CBR Institute for Biomedical Research, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA
Annu Rev Biomed Eng 8:377-402. 2006..Pilot siRNA clinical studies began just three years after the discovery that RNAi works in mammalian cells. This review discusses recent progress and obstacles to using siRNAs as small molecule drugs...- MicroRNAs in viral replication and pathogenesisDerek M Dykxhoorn
The CBR Institute for Biomedical Research, Harvard Medical School, Boston, Massachusetts, USA
DNA Cell Biol 26:239-49. 2007.... - The silent revolution: RNA interference as basic biology, research tool, and therapeuticDerek M Dykxhoorn
CBR Institute for Biomedical Research and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA
Annu Rev Med 56:401-23. 2005..RNAi may provide an important new therapeutic modality for treating infection, cancer, neurodegenerative disease, and other illnesses, although in vivo delivery of small interfering RNAs into cells remains a significant obstacle... - miR-24-mediated downregulation of H2AX suppresses DNA repair in terminally differentiated blood cellsAshish Lal
Immune Disease Institute and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
Nat Struct Mol Biol 16:492-8. 2009..Therefore, miR-24 upregulation in postreplicative cells reduces H2AX and makes them vulnerable to DNA damage... - Sustained small interfering RNA-mediated human immunodeficiency virus type 1 inhibition in primary macrophagesErwei Song
Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115, USA
J Virol 77:7174-81. 2003..Under these circumstances, long-term suppression of HIV replication could be achieved with p24 siRNA. Thus, siRNAs can induce potent and long-lasting HIV inhibition in nondividing cells such as macrophages... - Knocking down disease with siRNAsDerek M Dykxhoorn
CBR Institute for Biomedical Research and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Cell 126:231-5. 2006..This Essay will examine the opportunities for harnessing RNA interference (RNAi) for therapy, as well as the obstacles and possible ways to circumvent them... - Identification of host proteins required for HIV infection through a functional genomic screenAbraham L Brass
Department of Genetics, Center for Genetics and Genomics, Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
Science 319:921-6. 2008..This effort illustrates the power with which RNA interference and forward genetics can be used to expose the dependencies of human pathogens such as HIV, and in so doing identify potential targets for therapy... - Lentiviral delivery of short hairpin RNAs protects CD4 T cells from multiple clades and primary isolates of HIVSang Kyung Lee
The CBR Institute for Biomedical Research, 800 Huntington Ave, Boston, MA 02115, USA
Blood 106:818-26. 2005..Thus, although 1 or 2 mutations at peripheral sites are tolerated, mutations in the central target cleavage region abolish RNAi activity... - Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptorsErwei Song
CBR Institute for Biomedical Research and Department of Pediatrics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
Nat Biotechnol 23:709-17. 2005..Furthermore, an ErbB2 single-chain antibody fused with protamine delivered siRNAs specifically into ErbB2-expressing cancer cells. This study demonstrates the potential for systemic, cell-type specific, antibody-mediated siRNA delivery... - miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to "seedless" 3'UTR microRNA recognition elementsAshish Lal
Immune Disease Institute, Children s Hospital Boston, Department of Pediatrics, Harvard Medical School, MA 02115, USA
Mol Cell 35:610-25. 2009..The E2F2 3'UTR lacks a predicted miR-24 recognition element. In fact, miR-24 regulates expression of E2F2, MYC, AURKB, CCNA2, CDC2, CDK4, and FEN1 by recognizing seedless but highly complementary sequences... - miR-200 enhances mouse breast cancer cell colonization to form distant metastasesDerek M Dykxhoorn
Department of Pediatrics, Immune Disease Institute, Harvard Medical School, Boston, Massachusetts, United States of America
PLoS ONE 4:e7181. 2009..Because some miRNAs are dysregulated in cancer and affect cellular transformation, tumor formation, and metastasis, we examined whether changes in miRNA expression might explain the differences in metastasis of these cells... - Silencing viral infectionDerek M Dykxhoorn
CBR Institute for Biomedical Research and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
PLoS Med 3:e242. 2006 - A PP4-phosphatase complex dephosphorylates gamma-H2AX generated during DNA replicationDipanjan Chowdhury
Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA
Mol Cell 31:33-46. 2008..Therefore, gamma-H2AX elimination at DNA damage foci is required for DNA damage repair, but accomplishing this task involves distinct phosphatases with potentially overlapping roles... - Determinants of specific RNA interference-mediated silencing of human beta-globin alleles differing by a single nucleotide polymorphismDerek M Dykxhoorn
CBR Institute for Biomedical Research and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 103:5953-8. 2006.... - RNA interference and cancer: endogenous pathways and therapeutic approachesDerek M Dykxhoorn
Institute for Biomedical Research and Department of Pediatrics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
Adv Exp Med Biol 615:299-329. 2008..Possible strategies and obstacles to harnessing RNAi for cancer therapy will also be discussed... - Granzyme A cleaves a mitochondrial complex I protein to initiate caspase-independent cell deathDenis Martinvalet
Immune Disease Institute and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Cell 133:681-92. 2008..Target cells expressing a cleavage site mutant of NDUFS3 are resistant to GzmA-mediated cell death but remain sensitive to GzmB... - siRNA-directed inhibition of HIV-1 infectionCarl D Novina
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
Nat Med 8:681-6. 2002..siRNAs effectively inhibit pre- and/or post-integration infection events in the HIV-1 life cycle. Thus, siRNAs may have potential for therapeutic intervention in HIV-1 and other viral infections... - Inhibition of HIV transmission in human cervicovaginal explants and humanized mice using CD4 aptamer-siRNA chimerasLee Adam Wheeler
Immune Disease Institute and Program in Cellular and Molecular Medicine, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA
J Clin Invest 121:2401-12. 2011..When applied intravaginally to humanized mice, CD4-AsiCs protected against HIV vaginal transmission. Thus, CD4-AsiCs could be used as the active ingredient of a microbicide to prevent HIV sexual transmission... - Killing the messenger: short RNAs that silence gene expressionDerek M Dykxhoorn
Center for Cancer Research, Massachusetts Institute of Technology, 40 Ames Street, E17-529, Cambridge, Massachusetts 02139, USA
Nat Rev Mol Cell Biol 4:457-67. 2003..Much of the promise of RNA interference will depend on the recent advances in short-RNA-based silencing technologies... - Genetic analysis of the subunit organization and function of the conserved oligomeric golgi (COG) complex: studies of COG5- and COG7-deficient mammalian cellsToshihiko Oka
Department of Biology and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
J Biol Chem 280:32736-45. 2005..Only one or two of the seven Cog1- or Cog2-dependent Golgi membrane proteins called GEARs are also sensitive to Cog5 or Cog7 deficiency, indicating that the COG subunits play distinctive roles in controlling Golgi structure and function... - Lentivirus-delivered stable gene silencing by RNAi in primary cellsSheila A Stewart
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
RNA 9:493-501. 2003....