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    Michael McManus, PhD

    TitleAssociate Professor in Residence
    SchoolUCSF School of Medicine
    DepartmentDiabetes Center
    Address513 Parnassus Ave
    San Francisco CA 94143
    Phone415-502-2049

       Overview 
       Overview
      The McManus lab studies the basic biological processes relating to noncoding RNAs, using cultured cells and the mouse as a model. This includes the study of microRNAs, and the factors involved in small RNA production and activity. In a broad sense, the lab is interested in understanding how noncoding RNAs contribute to the specification of cell fate and function, for example, how deregulation of microRNAs may contribute to human disease.

      Based on our studies of noncoding RNA biology, we have developed cutting-edge research tools and agents for the interrogation of gene function and the potential use in the intervention of human disease. We focus on small RNAs from both a tool and biology standpoint. Two current project areas are below:

      Mouse knockouts of microRNAs. We have generated conditional mouse knockouts for Dicer, the catalytic engine of small RNA production in cells. We have used this mouse to explore the role of Dicer in many tissues and it is clear that it is key for normal cellular function in a broad array of tissues. However this is a low-resolution model for exploring small RNA biology, since many biologically important small RNAs are simultaneously depleted. For this reason, hundreds of conditional mouse small RNA knockout models are individually being made. Projects are available to phenotype these novel reagents.

      RNAi libraries. One active effort in my lab relates to the derivation and use of whole-genome shRNA libraries that we have generated- these are powerful tools to interrogate gene function in cells. This is a unique resource since it contains large numbers of shRNAs that allow for the statistical de-convolution of hits using deep sequencing. Projects are available that center on genome-wide RNAi interrogation of gene function, particularly as it relates to the molecular dissection of the regulation of gene expression.


       Bibliographic 
       Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
      List All   |   Timeline
      1. Bassik MC, Kampmann M, Lebbink RJ, Wang S, Hein MY, Poser I, Weibezahn J, Horlbeck MA, Chen S, Mann M, Hyman AA, Leproust EM, McManus MT, Weissman JS. A systematic Mammalian genetic interaction map reveals pathways underlying ricin susceptibility. Cell. 2013 Feb 14; 152(4):909-22.
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      2. Bronevetsky Y, Villarino AV, Eisley CJ, Barbeau R, Barczak AJ, Heinz GA, Kremmer E, Heissmeyer V, McManus MT, Erle DJ, Rao A, Ansel KM. T cell activation induces proteasomal degradation of Argonaute and rapid remodeling of the microRNA repertoire. J Exp Med. 2013 Feb 11; 210(2):417-32.
        View in: PubMed
      3. Upton JP, Wang L, Han D, Wang ES, Huskey NE, Lim L, Truitt M, McManus MT, Ruggero D, Goga A, Papa FR, Oakes SA. IRE1a cleaves select microRNAs during ER stress to derepress translation of proapoptotic Caspase-2. Science. 2012 Nov 9; 338(6108):818-22.
        View in: PubMed
      4. Ku GM, Kim H, Vaughn IW, Hangauer MJ, Myung Oh C, German MS, McManus MT. Research resource: RNA-Seq reveals unique features of the pancreatic ß-cell transcriptome. Mol Endocrinol. 2012 Oct; 26(10):1783-92.
        View in: PubMed
      5. Repetto E, Briata P, Kuziner N, Harfe BD, McManus MT, Gherzi R, Rosenfeld MG, Trabucchi M. Let-7b/c enhance the stability of a tissue-specific mRNA during mammalian organogenesis as part of a feedback loop involving KSRP. PLoS Genet. 2012; 8(7):e1002823.
        View in: PubMed
      6. Dallas A, Ilves H, Ge Q, Kumar P, Shorenstein J, Kazakov SA, Cuellar TL, McManus MT, Behlke MA, Johnston BH. Right- and left-loop short shRNAs have distinct and unusual mechanisms of gene silencing. Nucleic Acids Res. 2012 Oct; 40(18):9255-71.
        View in: PubMed
      7. Park CY, Jeker LT, Carver-Moore K, Oh A, Liu HJ, Cameron R, Richards H, Li Z, Adler D, Yoshinaga Y, Martinez M, Nefadov M, Abbas AK, Weiss A, Lanier LL, de Jong PJ, Bluestone JA, Srivastava D, McManus MT. A resource for the conditional ablation of microRNAs in the mouse. Cell Rep. 2012 Apr 19; 1(4):385-91.
        View in: PubMed
      8. Liu X, Jin DY, McManus MT, Mourelatos Z. Precursor microRNA-programmed silencing complex assembly pathways in mammals. Mol Cell. 2012 May 25; 46(4):507-17.
        View in: PubMed
      9. Choi YS, Patena W, Leavitt AD, McManus MT. Widespread RNA 3'-end oligouridylation in mammals. RNA. 2012 Mar; 18(3):394-401.
        View in: PubMed
      10. Ku GM, Pappalardo Z, Luo CC, German MS, McManus MT. An siRNA screen in pancreatic beta cells reveals a role for Gpr27 in insulin production. PLoS Genet. 2012 Jan; 8(1):e1002449.
        View in: PubMed
      11. Lebbink RJ, Lowe M, Chan T, Khine H, Wang X, McManus MT. Polymerase II promoter strength determines efficacy of microRNA adapted shRNAs. PLoS One. 2011; 6(10):e26213.
        View in: PubMed
      12. Zhang Z, O'Rourke JR, McManus MT, Lewandoski M, Harfe BD, Sun X. The microRNA-processing enzyme Dicer is dispensable for somite segmentation but essential for limb bud positioning. Dev Biol. 2011 Mar 15; 351(2):254-65.
        View in: PubMed
      13. Villarino AV, Katzman SD, Gallo E, Miller O, Jiang S, McManus MT, Abbas AK. Posttranscriptional silencing of effector cytokine mRNA underlies the anergic phenotype of self-reactive T cells. Immunity. 2011 Jan 28; 34(1):50-60.
        View in: PubMed
      14. Park CY, Choi YS, McManus MT. Analysis of microRNA knockouts in mice. Hum Mol Genet. 2010 Oct 15; 19(R2):R169-75.
        View in: PubMed
      15. Dugas JC, Cuellar TL, Scholze A, Ason B, Ibrahim A, Emery B, Zamanian JL, Foo LC, McManus MT, Barres BA. Dicer1 and miR-219 Are required for normal oligodendrocyte differentiation and myelination. Neuron. 2010 Mar 11; 65(5):597-611.
        View in: PubMed
      16. Shin D, Shin JY, McManus MT, Ptácek LJ, Fu YH. Dicer ablation in oligodendrocytes provokes neuronal impairment in mice. Ann Neurol. 2009 Dec; 66(6):843-57.
        View in: PubMed
      17. Tan GS, Garchow BG, Liu X, Yeung J, Morris JP, Cuellar TL, McManus MT, Kiriakidou M. Expanded RNA-binding activities of mammalian Argonaute 2. Nucleic Acids Res. 2009 Dec; 37(22):7533-45.
        View in: PubMed
      18. Sekine S, Ogawa R, Mcmanus MT, Kanai Y, Hebrok M. Dicer is required for proper liver zonation. J Pathol. 2009 Nov; 219(3):365-72.
        View in: PubMed
      19. Wang X, McManus M. Lentivirus production. J Vis Exp. 2009; (32).
        View in: PubMed
      20. Gaspar-Maia A, Alajem A, Polesso F, Sridharan R, Mason MJ, Heidersbach A, Ramalho-Santos J, McManus MT, Plath K, Meshorer E, Ramalho-Santos M. Chd1 regulates open chromatin and pluripotency of embryonic stem cells. Nature. 2009 Aug 13; 460(7257):863-8.
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      21. Bassik MC, Lebbink RJ, Churchman LS, Ingolia NT, Patena W, LeProust EM, Schuldiner M, Weissman JS, McManus MT. Rapid creation and quantitative monitoring of high coverage shRNA libraries. Nat Methods. 2009 Jun; 6(6):443-5.
        View in: PubMed
      22. Ruggiero T, Trabucchi M, De Santa F, Zupo S, Harfe BD, McManus MT, Rosenfeld MG, Briata P, Gherzi R. LPS induces KH-type splicing regulatory protein-dependent processing of microRNA-155 precursors in macrophages. FASEB J. 2009 Sep; 23(9):2898-908.
        View in: PubMed
      23. Huang TH, Wu F, Loeb GB, Hsu R, Heidersbach A, Brincat A, Horiuchi D, Lebbink RJ, Mo YY, Goga A, McManus MT. Up-regulation of miR-21 by HER2/neu signaling promotes cell invasion. J Biol Chem. 2009 Jul 3; 284(27):18515-24.
        View in: PubMed
      24. Sekine S, Ogawa R, Ito R, Hiraoka N, McManus MT, Kanai Y, Hebrok M. Disruption of Dicer1 induces dysregulated fetal gene expression and promotes hepatocarcinogenesis. Gastroenterology. 2009 Jun; 136(7):2304-2315.e1-4.
        View in: PubMed
      25. Binnie JE, McManus MT. Characterization of the 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase multigene family of Malus domestica Borkh. Phytochemistry. 2009 Feb; 70(3):348-60.
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      26. Soukup GA, Fritzsch B, Pierce ML, Weston MD, Jahan I, McManus MT, Harfe BD. Residual microRNA expression dictates the extent of inner ear development in conditional Dicer knockout mice. Dev Biol. 2009 Apr 15; 328(2):328-41.
        View in: PubMed
      27. Pastorelli LM, Wells S, Fray M, Smith A, Hough T, Harfe BD, McManus MT, Smith L, Woolf AS, Cheeseman M, Greenfield A. Genetic analyses reveal a requirement for Dicer1 in the mouse urogenital tract. Mamm Genome. 2009 Mar; 20(3):140-51.
        View in: PubMed
      28. Papaioannou MD, Pitetti JL, Ro S, Park C, Aubry F, Schaad O, Vejnar CE, Kühne F, Descombes P, Zdobnov EM, McManus MT, Guillou F, Harfe BD, Yan W, Jégou B, Nef S. Sertoli cell Dicer is essential for spermatogenesis in mice. Dev Biol. 2009 Feb 1; 326(1):250-9.
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      29. Harvey SJ, Jarad G, Cunningham J, Goldberg S, Schermer B, Harfe BD, McManus MT, Benzing T, Miner JH. Podocyte-specific deletion of dicer alters cytoskeletal dynamics and causes glomerular disease. J Am Soc Nephrol. 2008 Nov; 19(11):2150-8.
        View in: PubMed
      30. Zhou X, Jeker LT, Fife BT, Zhu S, Anderson MS, McManus MT, Bluestone JA. Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity. J Exp Med. 2008 Sep 1; 205(9):1983-91.
        View in: PubMed
      31. Maatouk DM, Loveland KL, McManus MT, Moore K, Harfe BD. Dicer1 is required for differentiation of the mouse male germline. Biol Reprod. 2008 Oct; 79(4):696-703.
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      32. Reid JG, Nagaraja AK, Lynn FC, Drabek RB, Muzny DM, Shaw CA, Weiss MK, Naghavi AO, Khan M, Zhu H, Tennakoon J, Gunaratne GH, Corry DB, Miller J, McManus MT, German MS, Gibbs RA, Matzuk MM, Gunaratne PH. Mouse let-7 miRNA populations exhibit RNA editing that is constrained in the 5'-seed/ cleavage/anchor regions and stabilize predicted mmu-let-7a:mRNA duplexes. Genome Res. 2008 Oct; 18(10):1571-81.
        View in: PubMed
      33. Damiani D, Alexander JJ, O'Rourke JR, McManus M, Jadhav AP, Cepko CL, Hauswirth WW, Harfe BD, Strettoi E. Dicer inactivation leads to progressive functional and structural degeneration of the mouse retina. J Neurosci. 2008 May 7; 28(19):4878-87.
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      34. Davis TH, Cuellar TL, Koch SM, Barker AJ, Harfe BD, McManus MT, Ullian EM. Conditional loss of Dicer disrupts cellular and tissue morphogenesis in the cortex and hippocampus. J Neurosci. 2008 Apr 23; 28(17):4322-30.
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      35. Cuellar TL, Davis TH, Nelson PT, Loeb GB, Harfe BD, Ullian E, McManus MT. Dicer loss in striatal neurons produces behavioral and neuroanatomical phenotypes in the absence of neurodegeneration. Proc Natl Acad Sci U S A. 2008 Apr 8; 105(14):5614-9.
        View in: PubMed
      36. McManus MT. Michael T. McManus: Interrupting biology [interview by Hema Bashyam]. J Exp Med. 2008 Mar 17; 205(3):506-7.
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      37. Osokine I, Hsu R, Loeb GB, McManus MT. Unintentional miRNA ablation is a risk factor in gene knockout studies: a short report. PLoS Genet. 2008 Feb; 4(2):e34.
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      38. Choi PS, Zakhary L, Choi WY, Caron S, Alvarez-Saavedra E, Miska EA, McManus M, Harfe B, Giraldez AJ, Horvitz HR, Schier AF, Dulac C. Members of the miRNA-200 family regulate olfactory neurogenesis. Neuron. 2008 Jan 10; 57(1):41-55.
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      39. Ku G, McManus MT. Behind the scenes of a small RNA gene-silencing pathway. Hum Gene Ther. 2008 Jan; 19(1):17-26.
        View in: PubMed
      40. McManus MT. Further examination of abscission zone cells as ethylene target cells in higher plants. Ann Bot. 2008 Jan; 101(2):285-92.
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      41. Lynn FC, Skewes-Cox P, Kosaka Y, McManus MT, Harfe BD, German MS. MicroRNA expression is required for pancreatic islet cell genesis in the mouse. Diabetes. 2007 Dec; 56(12):2938-45.
        View in: PubMed
      42. O'Rourke JR, Georges SA, Seay HR, Tapscott SJ, McManus MT, Goldhamer DJ, Swanson MS, Harfe BD. Essential role for Dicer during skeletal muscle development. Dev Biol. 2007 Nov 15; 311(2):359-68.
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      43. Cumming M, Leung S, McCallum J, McManus MT. Complex formation between recombinant ATP sulfurylase and APS reductase of Allium cepa (L.). FEBS Lett. 2007 Sep 4; 581(22):4139-47.
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      44. Nawroth R, van Zante A, Cervantes S, McManus M, Hebrok M, Rosen SD. Extracellular sulfatases, elements of the Wnt signaling pathway, positively regulate growth and tumorigenicity of human pancreatic cancer cells. PLoS One. 2007; 2(4):e392.
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      45. Crittenden JR, Heidersbach A, McManus MT. Lentiviral strategies for RNAi knockdown of neuronal genes. Curr Protoc Neurosci. 2007 Apr; Chapter 5:Unit 5.26.
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      46. Zhao Y, Ransom JF, Li A, Vedantham V, von Drehle M, Muth AN, Tsuchihashi T, McManus MT, Schwartz RJ, Srivastava D. Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell. 2007 Apr 20; 129(2):303-17.
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      47. Harper RW, Xu C, McManus M, Heidersbach A, Eiserich JP. Duox2 exhibits potent heme peroxidase activity in human respiratory tract epithelium. FEBS Lett. 2006 Oct 2; 580(22):5150-4.
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      48. Heidersbach A, Gaspar-Maia A, McManus MT, Ramalho-Santos M. RNA interference in embryonic stem cells and the prospects for future therapies. Gene Ther. 2006 Mar; 13(6):478-86.
        View in: PubMed
      49. Harris KS, Zhang Z, McManus MT, Harfe BD, Sun X. Dicer function is essential for lung epithelium morphogenesis. Proc Natl Acad Sci U S A. 2006 Feb 14; 103(7):2208-13.
        View in: PubMed
      50. Cuellar TL, McManus MT. MicroRNAs and endocrine biology. J Endocrinol. 2005 Dec; 187(3):327-32.
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      51. Hornstein E, Mansfield JH, Yekta S, Hu JK, Harfe BD, McManus MT, Baskerville S, Bartel DP, Tabin CJ. The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development. Nature. 2005 Dec 1; 438(7068):671-4.
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      52. Morris JP, McManus MT. Slowing down the Ras lane: miRNAs as tumor suppressors? Sci STKE. 2005 Aug 16; 2005(297):pe41.
        View in: PubMed
      53. Hong JH, Hwang ES, McManus MT, Amsterdam A, Tian Y, Kalmukova R, Mueller E, Benjamin T, Spiegelman BM, Sharp PA, Hopkins N, Yaffe MB. TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science. 2005 Aug 12; 309(5737):1074-8.
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      54. Harfe BD, McManus MT, Mansfield JH, Hornstein E, Tabin CJ. The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Proc Natl Acad Sci U S A. 2005 Aug 2; 102(31):10898-903.
        View in: PubMed
      55. McManus MT. Small RNAs and immunity. Immunity. 2004 Dec; 21(6):747-56.
        View in: PubMed
      56. Mansfield JH, Harfe BD, Nissen R, Obenauer J, Srineel J, Chaudhuri A, Farzan-Kashani R, Zuker M, Pasquinelli AE, Ruvkun G, Sharp PA, Tabin CJ, McManus MT. MicroRNA-responsive 'sensor' transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression. Nat Genet. 2004 Oct; 36(10):1079-83.
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      57. Ventura A, Meissner A, Dillon CP, McManus M, Sharp PA, Van Parijs L, Jaenisch R, Jacks T. Cre-lox-regulated conditional RNA interference from transgenes. Proc Natl Acad Sci U S A. 2004 Jul 13; 101(28):10380-5.
        View in: PubMed
      58. McManus MT. MicroRNAs and cancer. Semin Cancer Biol. 2003 Aug; 13(4):253-8.
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      59. Ge Q, McManus MT, Nguyen T, Shen CH, Sharp PA, Eisen HN, Chen J. RNA interference of influenza virus production by directly targeting mRNA for degradation and indirectly inhibiting all viral RNA transcription. Proc Natl Acad Sci U S A. 2003 Mar 4; 100(5):2718-23.
        View in: PubMed
      60. Rubinson DA, Dillon CP, Kwiatkowski AV, Sievers C, Yang L, Kopinja J, Rooney DL, Zhang M, Ihrig MM, McManus MT, Gertler FB, Scott ML, Van Parijs L. A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference. Nat Genet. 2003 Mar; 33(3):401-6.
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      61. McManus MT, Haines BB, Dillon CP, Whitehurst CE, van Parijs L, Chen J, Sharp PA. Small interfering RNA-mediated gene silencing in T lymphocytes. J Immunol. 2002 Nov 15; 169(10):5754-60.
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      62. McManus MT, Sharp PA. Gene silencing in mammals by small interfering RNAs. Nat Rev Genet. 2002 Oct; 3(10):737-47.
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      63. Chen Z, Indjeian VB, McManus M, Wang L, Dynlacht BD. CP110, a cell cycle-dependent CDK substrate, regulates centrosome duplication in human cells. Dev Cell. 2002 Sep; 3(3):339-50.
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      64. McManus MT, Petersen CP, Haines BB, Chen J, Sharp PA. Gene silencing using micro-RNA designed hairpins. RNA. 2002 Jun; 8(6):842-50.
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      65. McManus MT, Shimamura M, Grams J, Hajduk SL. Identification of candidate mitochondrial RNA editing ligases from Trypanosoma brucei. RNA. 2001 Feb; 7(2):167-75.
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      66. Grams J, McManus MT, Hajduk SL. Processing of polycistronic guide RNAs is associated with RNA editing complexes in Trypanosoma brucei. EMBO J. 2000 Oct 16; 19(20):5525-32.
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      67. McManus MT, Adler BK, Pollard VW, Hajduk SL. Trypanosoma brucei guide RNA poly(U) tail formation is stabilized by cognate mRNA. Mol Cell Biol. 2000 Feb; 20(3):883-91.
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      68. Sabatini RS, Adler BK, Madison-Antenucci S, McManus MT, Hajduk SL. Biochemical methods for analysis of kinetoplastid RNA editing. Methods. 1998 May; 15(1):15-26.
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      69. Hajduk SL, Adler B, Madison-Antenucci S, McManus M, Sabatini R. Insertional and deletional RNA editing in trypanosome mitochondria. Nucleic Acids Symp Ser. 1997; (36):15-8.
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