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    Victor R Ambros PhD

    TitleProfessor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentProgram in Molecular Medicine
    AddressUniversity of Massachusetts Medical School
    373 Plantation Street
    Worcester MA 01605
    Phone508-856-6380
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentBioinformatics and Computational Biology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMD/PhD Program

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentBioinformatics and Integrative Biology

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentRNA Therapeutics Institute

        Overview 
        Narrative

        Biography

        Victor Ambros grew up in Vermont and graduated from MIT in 1975. He did his graduate research (1976-1979) with David Baltimore at MIT, studying poliovirus genome structure and replication. He began to study the genetic pathways controlling developmental timing in the nematode C. elegans as a postdoc in H. Robert Horvitz's lab at MIT, and continued those studies while on the faculty of Harvard (1984-1992), Dartmouth (1992-2007), and the University of Massachusetts Medical School (2008-present). In 1993, members of the Ambros lab identified the first microRNA, the product of lin-4, a heterochronic gene of C. elegans. Since then, the role of microRNAs in development has been a major focus of his research.

        Silverman Professor of Natural Sciences, Co-Director RNA Therapeutics Institute (RTI)

        Ambros Lab Web Page

        Molecular and genetic control of animal development; microRNA regulatory mechanisms

        We are interested in the genetic regulatory mechanisms that control animal development, and in particular the molecules that function during animal development to ensure the proper timing of developmental events. We have primarily employed the nematode Caenorhabditis elegans as a model system for studying the function of regulators of developmental timing, which in C. elegans are known as the “heterochronic genes”, in reference to the remarkable changes in relative timing of developmental event that are elicited by mutations in these genes. The heterochronic genes comprise a set of interrelated regulatory pathways that include proteins that regulate the transcription of other genes, and also a class of small RNA, known as microRNAs, that regulate the production of protein by the messenger RNAs of specific target genes. Much of our research in recent years has been aimed at understanding how microRNAs are integrated into broader regulatory networks related to animal development and human disease, and at uncovering the molecular mechanisms for how microRNAs exert their effects on gene expression.

        Victor's Worms



        Rotation Projects

        Rotations

        Project 1: Genetic screens for proteins that modify or regulate the activity of microRNAs in C. elegans.



        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Ward J, Kanchagar C, Veksler-Lublinsky I, Lee RC, McGill MR, Jaeschke H, Curry SC, Ambros VR. Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis. Proc Natl Acad Sci U S A. 2014 Aug 19; 111(33):12169-74.
          View in: PubMed
        2. Zinovyeva AY, Bouasker S, Simard MJ, Hammell CM, Ambros V. Mutations in Conserved Residues of the C. elegans microRNA Argonaute ALG-1 Identify Separable Functions in ALG-1 miRISC Loading and Target Repression. PLoS Genet. 2014 Apr; 10(4):e1004286.
          View in: PubMed
        3. Ambros V. Victor Ambros: the broad scope of microRNAs. Interview by Caitlin Sedwick. J Cell Biol. 2013 May 13; 201(4):492-3.
          View in: PubMed
        4. Zou Y, Chiu H, Zinovyeva A, Ambros V, Chuang CF, Chang C. Developmental decline in neuronal regeneration by the progressive change of two intrinsic timers. Science. 2013 Apr 19; 340(6130):372-6.
          View in: PubMed
        5. Bossé GD, Rüegger S, Ow MC, Vasquez-Rifo A, Rondeau EL, Ambros VR, Grosshans H, Simard MJ. The decapping scavenger enzyme DCS-1 controls microRNA levels in Caenorhabditis elegans. Mol Cell. 2013 Apr 25; 50(2):281-7.
          View in: PubMed
        6. Karp X, Ambros V. Dauer larva quiescence alters the circuitry of microRNA pathways regulating cell fate progression in C. elegans. Development. 2012 Jun; 139(12):2177-86.
          View in: PubMed
        7. McManus DD, Ambros V. Circulating MicroRNAs in cardiovascular disease. Circulation. 2011 Nov 1; 124(18):1908-10.
          View in: PubMed
        8. Ambros V. MicroRNAs and developmental timing. Curr Opin Genet Dev. 2011 Aug; 21(4):511-7.
          View in: PubMed
        9. Karp X, Hammell M, Ow MC, Ambros V. Effect of life history on microRNA expression during C. elegans development. RNA. 2011 Apr; 17(4):639-51.
          View in: PubMed
        10. Karp X, Ambros V. The developmental timing regulator HBL-1 modulates the dauer formation decision in Caenorhabditis elegans. Genetics. 2011 Jan; 187(1):345-53.
          View in: PubMed
        11. Ambros V. MicroRNAs: genetically sensitized worms reveal new secrets. Curr Biol. 2010 Jul 27; 20(14):R598-600.
          View in: PubMed
        12. Zheng G, Ambros V, Li WH. Inhibiting miRNA in Caenorhabditis elegans using a potent and selective antisense reagent. Silence. 2010; 1(1):9.
          View in: PubMed
        13. Ambros V. In the tradition of science: an interview with Victor Ambros. PLoS Genet. 2010 Mar; 6(3):e1000853.
          View in: PubMed
        14. Ambros V. pRB/CKI pathways at the interface of cell cycle and development. Cell Cycle. 2009 Nov 1; 8(21):3433-4.
          View in: PubMed
        15. Hammell CM, Karp X, Ambros V. A feedback circuit involving let-7-family miRNAs and DAF-12 integrates environmental signals and developmental timing in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2009 Nov 3; 106(44):18668-73.
          View in: PubMed
        16. Hong X, Hammell M, Ambros V, Cohen SM. Immunopurification of Ago1 miRNPs selects for a distinct class of microRNA targets. Proc Natl Acad Sci U S A. 2009 Sep 1; 106(35):15085-90.
          View in: PubMed
        17. Zhang L, Hammell M, Kudlow BA, Ambros V, Han M. Systematic analysis of dynamic miRNA-target interactions during C. elegans development. Development. 2009 Sep; 136(18):3043-55.
          View in: PubMed
        18. Hammell CM, Lubin I, Boag PR, Blackwell TK, Ambros V. nhl-2 Modulates microRNA activity in Caenorhabditis elegans. Cell. 2009 Mar 6; 136(5):926-38.
          View in: PubMed
        19. Martinez NJ, Ow MC, Reece-Hoyes JS, Barrasa MI, Ambros VR, Walhout AJ. Genome-scale spatiotemporal analysis of Caenorhabditis elegans microRNA promoter activity. Genome Res. 2008 Dec; 18(12):2005-15.
          View in: PubMed
        20. Ambros V. The evolution of our thinking about microRNAs. Nat Med. 2008 Oct; 14(10):1036-40.
          View in: PubMed
        21. Ow MC, Martinez NJ, Olsen PH, Silverman HS, Barrasa MI, Conradt B, Walhout AJ, Ambros V. The FLYWCH transcription factors FLH-1, FLH-2, and FLH-3 repress embryonic expression of microRNA genes in C. elegans. Genes Dev. 2008 Sep 15; 22(18):2520-34.
          View in: PubMed
        22. Martinez NJ, Ow MC, Barrasa MI, Hammell M, Sequerra R, Doucette-Stamm L, Roth FP, Ambros VR, Walhout AJ. A C. elegans genome-scale microRNA network contains composite feedback motifs with high flux capacity. Genes Dev. 2008 Sep 15; 22(18):2535-49.
          View in: PubMed
        23. Hammell M, Long D, Zhang L, Lee A, Carmack CS, Han M, Ding Y, Ambros V. mirWIP: microRNA target prediction based on microRNA-containing ribonucleoprotein-enriched transcripts. Nat Methods. 2008 Sep; 5(9):813-9.
          View in: PubMed
        24. Sokol NS, Xu P, Jan YN, Ambros V. Drosophila let-7 microRNA is required for remodeling of the neuromusculature during metamorphosis. Genes Dev. 2008 Jun 15; 22(12):1591-6.
          View in: PubMed
        25. Miska EA, Alvarez-Saavedra E, Abbott AL, Lau NC, Hellman AB, McGonagle SM, Bartel DP, Ambros VR, Horvitz HR. Most Caenorhabditis elegans microRNAs are individually not essential for development or viability. PLoS Genet. 2007 Dec; 3(12):e215.
          View in: PubMed
        26. Hinas A, Reimegård J, Wagner EG, Nellen W, Ambros VR, Söderbom F. The small RNA repertoire of Dictyostelium discoideum and its regulation by components of the RNAi pathway. Nucleic Acids Res. 2007; 35(20):6714-26.
          View in: PubMed
        27. Ambros V, Chen X. The regulation of genes and genomes by small RNAs. Development. 2007 May; 134(9):1635-41.
          View in: PubMed
        28. Long D, Lee R, Williams P, Chan CY, Ambros V, Ding Y. Potent effect of target structure on microRNA function. Nat Struct Mol Biol. 2007 Apr; 14(4):287-94.
          View in: PubMed
        29. Gaur A, Jewell DA, Liang Y, Ridzon D, Moore JH, Chen C, Ambros VR, Israel MA. Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res. 2007 Mar 15; 67(6):2456-68.
          View in: PubMed
        30. Ambros V. The 2007 George W. Beadle Medal. Robert K. Herman. Genetics. 2007 Feb; 175(2):465-6.
          View in: PubMed
        31. Lee RC, Hammell CM, Ambros V. Interacting endogenous and exogenous RNAi pathways in Caenorhabditis elegans. RNA. 2006 Apr; 12(4):589-97.
          View in: PubMed
        32. Hristova M, Birse D, Hong Y, Ambros V. The Caenorhabditis elegans heterochronic regulator LIN-14 is a novel transcription factor that controls the developmental timing of transcription from the insulin/insulin-like growth factor gene ins-33 by direct DNA binding. Mol Cell Biol. 2005 Dec; 25(24):11059-72.
          View in: PubMed
        33. Karp X, Ambros V. Developmental biology. Encountering microRNAs in cell fate signaling. Science. 2005 Nov 25; 310(5752):1288-9.
          View in: PubMed
        34. Kuhlmann M, Borisova BE, Kaller M, Larsson P, Stach D, Na J, Eichinger L, Lyko F, Ambros V, Söderbom F, Hammann C, Nellen W. Silencing of retrotransposons in Dictyostelium by DNA methylation and RNAi. Nucleic Acids Res. 2005; 33(19):6405-17.
          View in: PubMed
        35. Sokol NS, Ambros V. Mesodermally expressed Drosophila microRNA-1 is regulated by Twist and is required in muscles during larval growth. Genes Dev. 2005 Oct 1; 19(19):2343-54.
          View in: PubMed
        36. Abbott AL, Alvarez-Saavedra E, Miska EA, Lau NC, Bartel DP, Horvitz HR, Ambros V. The let-7 MicroRNA family members mir-48, mir-84, and mir-241 function together to regulate developmental timing in Caenorhabditis elegans. Dev Cell. 2005 Sep; 9(3):403-14.
          View in: PubMed
        37. Ambros V. The functions of animal microRNAs. Nature. 2004 Sep 16; 431(7006):350-5.
          View in: PubMed
        38. Pepper AS, McCane JE, Kemper K, Yeung DA, Lee RC, Ambros V, Moss EG. The C. elegans heterochronic gene lin-46 affects developmental timing at two larval stages and encodes a relative of the scaffolding protein gephyrin. Development. 2004 May; 131(9):2049-59.
          View in: PubMed
        39. Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V. Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol. 2004; 5(3):R13.
          View in: PubMed
        40. Lee R, Feinbaum R, Ambros V. A short history of a short RNA. Cell. 2004 Jan 23; 116(2 Suppl):S89-92, 1 p following S96.
          View in: PubMed
        41. Ambros V, Lee RC. Identification of microRNAs and other tiny noncoding RNAs by cDNA cloning. Methods Mol Biol. 2004; 265:131-58.
          View in: PubMed
        42. Carrington JC, Ambros V. Role of microRNAs in plant and animal development. Science. 2003 Jul 18; 301(5631):336-8.
          View in: PubMed
        43. Sempere LF, Sokol NS, Dubrovsky EB, Berger EM, Ambros V. Temporal regulation of microRNA expression in Drosophila melanogaster mediated by hormonal signals and broad-Complex gene activity. Dev Biol. 2003 Jul 1; 259(1):9-18.
          View in: PubMed
        44. Ambros V. MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell. 2003 Jun 13; 113(6):673-6.
          View in: PubMed
        45. Ambros V, Lee RC, Lavanway A, Williams PT, Jewell D. MicroRNAs and other tiny endogenous RNAs in C. elegans. Curr Biol. 2003 May 13; 13(10):807-18.
          View in: PubMed
        46. Ambros V, Bartel B, Bartel DP, Burge CB, Carrington JC, Chen X, Dreyfuss G, Eddy SR, Griffiths-Jones S, Marshall M, Matzke M, Ruvkun G, Tuschl T. A uniform system for microRNA annotation. RNA. 2003 Mar; 9(3):277-9.
          View in: PubMed
        47. Sempere LF, Dubrovsky EB, Dubrovskaya VA, Berger EM, Ambros V. The expression of the let-7 small regulatory RNA is controlled by ecdysone during metamorphosis in Drosophila melanogaster. Dev Biol. 2002 Apr 1; 244(1):170-9.
          View in: PubMed
        48. Ambros V. microRNAs: tiny regulators with great potential. Cell. 2001 Dec 28; 107(7):823-6.
          View in: PubMed
        49. Lee RC, Ambros V. An extensive class of small RNAs in Caenorhabditis elegans. Science. 2001 Oct 26; 294(5543):862-4.
          View in: PubMed
        50. Ambros V. Development. Dicing up RNAs. Science. 2001 Aug 3; 293(5531):811-3.
          View in: PubMed
        51. Ambros V. The temporal control of cell cycle and cell fate in Caenorhabditis elegans. Novartis Found Symp. 2001; 237:203-14; discussion 214-20.
          View in: PubMed
        52. Ambros V. Control of developmental timing in Caenorhabditis elegans. Curr Opin Genet Dev. 2000 Aug; 10(4):428-33.
          View in: PubMed
        53. Slack FJ, Basson M, Liu Z, Ambros V, Horvitz HR, Ruvkun G. The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. Mol Cell. 2000 Apr; 5(4):659-69.
          View in: PubMed
        54. Hong Y, Lee RC, Ambros V. Structure and function analysis of LIN-14, a temporal regulator of postembryonic developmental events in Caenorhabditis elegans. Mol Cell Biol. 2000 Mar; 20(6):2285-95.
          View in: PubMed
        55. Olsen PH, Ambros V. The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol. 1999 Dec 15; 216(2):671-80.
          View in: PubMed
        56. Feinbaum R, Ambros V. The timing of lin-4 RNA accumulation controls the timing of postembryonic developmental events in Caenorhabditis elegans. Dev Biol. 1999 Jun 1; 210(1):87-95.
          View in: PubMed
        57. Ambros V. Cell cycle-dependent sequencing of cell fate decisions in Caenorhabditis elegans vulva precursor cells. Development. 1999 May; 126(9):1947-56.
          View in: PubMed
        58. Hong Y, Roy R, Ambros V. Developmental regulation of a cyclin-dependent kinase inhibitor controls postembryonic cell cycle progression in Caenorhabditis elegans. Development. 1998 Sep; 125(18):3585-97.
          View in: PubMed
        59. Moss EG, Lee RC, Ambros V. The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA. Cell. 1997 Mar 7; 88(5):637-46.
          View in: PubMed
        60. Euling S, Ambros V. Reversal of cell fate determination in Caenorhabditis elegans vulval development. Development. 1996 Aug; 122(8):2507-15.
          View in: PubMed
        61. Euling S, Ambros V. Heterochronic genes control cell cycle progress and developmental competence of C. elegans vulva precursor cells. Cell. 1996 Mar 8; 84(5):667-76.
          View in: PubMed
        62. Liu Z, Kirch S, Ambros V. The Caenorhabditis elegans heterochronic gene pathway controls stage-specific transcription of collagen genes. Development. 1995 Aug; 121(8):2471-8.
          View in: PubMed
        63. Rougvie AE, Ambros V. The heterochronic gene lin-29 encodes a zinc finger protein that controls a terminal differentiation event in Caenorhabditis elegans. Development. 1995 Aug; 121(8):2491-500.
          View in: PubMed
        64. Ambros V, Moss EG. Heterochronic genes and the temporal control of C. elegans development. Trends Genet. 1994 Apr; 10(4):123-7.
          View in: PubMed
        65. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993 Dec 3; 75(5):843-54.
          View in: PubMed
        66. Mello CC, Kramer JM, Stinchcomb D, Ambros V. Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J. 1991 Dec; 10(12):3959-70.
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        67. Papp A, Rougvie AE, Ambros V. Molecular cloning of lin-29, a heterochronic gene required for the differentiation of hypodermal cells and the cessation of molting in C.elegans. Nucleic Acids Res. 1991 Feb 11; 19(3):623-30.
          View in: PubMed
        68. Liu ZC, Ambros V. Heterochronic genes control the stage-specific initiation and expression of the dauer larva developmental program in Caenorhabditis elegans. Genes Dev. 1989 Dec; 3(12B):2039-49.
          View in: PubMed
        69. Hodgkin J, Papp A, Pulak R, Ambros V, Anderson P. A new kind of informational suppression in the nematode Caenorhabditis elegans. Genetics. 1989 Oct; 123(2):301-13.
          View in: PubMed
        70. Ambros V. A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C. elegans. Cell. 1989 Apr 7; 57(1):49-57.
          View in: PubMed
        71. Ruvkun G, Ambros V, Coulson A, Waterston R, Sulston J, Horvitz HR. Molecular genetics of the Caenorhabditis elegans heterochronic gene lin-14. Genetics. 1989 Mar; 121(3):501-16.
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        72. Ambros V, Horvitz HR. The lin-14 locus of Caenorhabditis elegans controls the time of expression of specific postembryonic developmental events. Genes Dev. 1987 Jun; 1(4):398-414.
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        73. Ambros V, Horvitz HR. Heterochronic mutants of the nematode Caenorhabditis elegans. Science. 1984 Oct 26; 226(4673):409-16.
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        74. Ambros V, Pettersson RF, Baltimore D. An enzymatic activity in uninfected cells that cleaves the linkage between poliovirion RNA and the 5' terminal protein. Cell. 1978 Dec; 15(4):1439-46.
          View in: PubMed
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