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    Craig Mello PhD

    TitleDistinguished Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentProgram in Molecular Medicine
    AddressUniversity of Massachusetts Medical School
    368 Plantatoin Street, Suite AS5-2047
    Worcester MA 01605
    Phone508-856-1602
      Other Positions
      InstitutionUMMS - School of Medicine
      DepartmentCell and Developmental Biology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentBioinformatics and Computational Biology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentCell Biology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentBioinformatics and Integrative Biology

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentCancer Center

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentCenter for AIDS Research

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentProgram in Cell Dynamics

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentRNA Therapeutics Institute

        Overview 
        Narrative

        Academic Background

        Blais University Chair in Molecular Medicine, Co-Director RNA Therapeutics Institute

        Dr. Craig C. Mello received his B.Sc. degree in Biochemistry from Brown University in 1982, and received his Ph.D. from Harvard University in 1990. From 1990 to 1994 he conducted postdoctoral research at the Fred Hutchinson Cancer Research Center in Seattle, WA. He has been a member of the University of Massachusetts Medical School faculty since 1995, and a Howard Hughes Medical Investigator since 2000. His pioneering research on RNAi, in collaboration with Dr. Andrew Fire, has been recognized with numerous awards culminating with the prestigious 2006 Nobel Prize in Physiology or Medicine.

        RNA-mediated Gene Regulation

        Photo: Craig Mello

        In much the same way that we use short search queries to navigate the World Wide Web, cells use short segments of genetic code to find and regulate matching information. The proteins that mediate these searches are highly conserved in plants and animals and are essential for viability and fertility. Craig Mello is investigating how these search mechanisms work and how organisms use them to regulate, share, and propagate genetic information.

        For more information about Dr. Mello's research, please visit his Howard Hughes Medical Institute page at:

        https://www.hhmi.org/research/rna-interference-and-development-c-elegans



        Rotation Projects

        Potential Rotation Projects:

        There are numerous potential rotation project available in the Mello lab:

        Projects include: Investigation of RNAi and related mechanisms, including Piwi Argonaute pathways and their affects on fertility and epigenetic inheritance; Investigation of germline determination and cell-fate specification during embryogenesis; the exploration of CRISPR mediated genome editing tools for C. elegans and other organisms; and finally the use of CRISPR to generate C. elegans models for human genetic disease.



        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Conte D, MacNeil LT, Walhout AJ, Mello CC. RNA Interference in Caenorhabditis elegans. Curr Protoc Mol Biol. 2015; 109:26.3.1-26.3.30.
          View in: PubMed
        2. Gammon DB, Duraffour S, Rozelle DK, Hehnly H, Sharma R, Sparks ME, West CC, Chen Y, Moresco JJ, Andrei G, Connor JH, Conte D, Gundersen-Rindal DE, Marshall WL, Yates JR, Silverman N, Mello CC. A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection. Elife. 2014; 3.
          View in: PubMed
        3. Kim H, Ishidate T, Ghanta KS, Seth M, Conte D, Shirayama M, Mello CC. A Co-CRISPR Strategy for Efficient Genome Editing in Caenorhabditis elegans. Genetics. 2014 Aug; 197(4):1069-80.
          View in: PubMed
        4. Ishidate T, Elewa A, Kim S, Mello CC, Shirayama M. Divide and differentiate: CDK/Cyclins and the art of development. Cell Cycle. 2014 May 1; 13(9):1384-91.
          View in: PubMed
        5. Seth M, Shirayama M, Gu W, Ishidate T, Conte D, Mello CC. The C. elegans CSR-1 argonaute pathway counteracts epigenetic silencing to promote germline gene expression. Dev Cell. 2013 Dec 23; 27(6):656-63.
          View in: PubMed
        6. Conine CC, Moresco JJ, Gu W, Shirayama M, Conte D, Yates JR, Mello CC. Argonautes Promote Male Fertility and Provide a Paternal Memory of Germline Gene Expression in C. elegans. Cell. 2013 Dec 19; 155(7):1532-44.
          View in: PubMed
        7. Ishidate T, Kim S, Mello C, Shirayama M. Inductive asymmetric cell division: The WRM leads the way. Worm. 2013 Oct 1; 2(4):e26276.
          View in: PubMed
        8. Kim S, Ishidate T, Sharma R, Soto MC, Conte D, Mello CC, Shirayama M. Wnt and CDK-1 regulate cortical release of WRM-1/ß-catenin to control cell division orientation in early Caenorhabditis elegans embryos. Proc Natl Acad Sci U S A. 2013 Mar 5; 110(10):E918-27.
          View in: PubMed
        9. Gu W, Lee HC, Chaves D, Youngman EM, Pazour GJ, Conte D, Mello CC. CapSeq and CIP-TAP identify Pol II start sites and reveal capped small RNAs as C. elegans piRNA precursors. Cell. 2012 Dec 21; 151(7):1488-500.
          View in: PubMed
        10. D'Ambrogio A, Gu W, Udagawa T, Mello CC, Richter JD. Specific miRNA stabilization by Gld2-catalyzed monoadenylation. Cell Rep. 2012 Dec 27; 2(6):1537-45.
          View in: PubMed
        11. Shirayama M, Seth M, Lee HC, Gu W, Ishidate T, Conte D, Mello CC. piRNAs initiate an epigenetic memory of nonself RNA in the C. elegans germline. Cell. 2012 Jul 6; 150(1):65-77.
          View in: PubMed
        12. Lee HC, Gu W, Shirayama M, Youngman E, Conte D, Mello CC. C. elegans piRNAs mediate the genome-wide surveillance of germline transcripts. Cell. 2012 Jul 6; 150(1):78-87.
          View in: PubMed
        13. Thivierge C, Makil N, Flamand M, Vasale JJ, Mello CC, Wohlschlegel J, Conte D, Duchaine TF. Tudor domain ERI-5 tethers an RNA-dependent RNA polymerase to DCR-1 to potentiate endo-RNAi. Nat Struct Mol Biol. 2012 Jan; 19(1):90-7.
          View in: PubMed
        14. Gu W, Claycomb JM, Batista PJ, Mello CC, Conte D. Cloning Argonaute-associated small RNAs from Caenorhabditis elegans. Methods Mol Biol. 2011; 725:251-80.
          View in: PubMed
        15. Xie J, Xie Q, Zhang H, Ameres SL, Hung JH, Su Q, He R, Mu X, Seher Ahmed S, Park S, Kato H, Li C, Mueller C, Mello CC, Weng Z, Flotte TR, Zamore PD, Gao G. MicroRNA-regulated, systemically delivered rAAV9: a step closer to CNS-restricted transgene expression. Mol Ther. 2011 Mar; 19(3):526-35.
          View in: PubMed
        16. Conte D, Mello CC. Primal RNAs: The end of the beginning? Cell. 2010 Feb 19; 140(4):452-4.
          View in: PubMed
        17. Conine CC, Batista PJ, Gu W, Claycomb JM, Chaves DA, Shirayama M, Mello CC. Argonautes ALG-3 and ALG-4 are required for spermatogenesis-specific 26G-RNAs and thermotolerant sperm in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2010 Feb 23; 107(8):3588-93.
          View in: PubMed
        18. Vasale JJ, Gu W, Thivierge C, Batista PJ, Claycomb JM, Youngman EM, Duchaine TF, Mello CC, Conte D. Sequential rounds of RNA-dependent RNA transcription drive endogenous small-RNA biogenesis in the ERGO-1/Argonaute pathway. Proc Natl Acad Sci U S A. 2010 Feb 23; 107(8):3582-7.
          View in: PubMed
        19. Liu J, Maduzia LL, Shirayama M, Mello CC. NMY-2 maintains cellular asymmetry and cell boundaries, and promotes a SRC-dependent asymmetric cell division. Dev Biol. 2010 Mar 15; 339(2):366-73.
          View in: PubMed
        20. Claycomb JM, Batista PJ, Pang KM, Gu W, Vasale JJ, van Wolfswinkel JC, Chaves DA, Shirayama M, Mitani S, Ketting RF, Conte D, Mello CC. The Argonaute CSR-1 and its 22G-RNA cofactors are required for holocentric chromosome segregation. Cell. 2009 Oct 2; 139(1):123-34.
          View in: PubMed
        21. Gu W, Shirayama M, Conte D, Vasale J, Batista PJ, Claycomb JM, Moresco JJ, Youngman EM, Keys J, Stoltz MJ, Chen CC, Chaves DA, Duan S, Kasschau KD, Fahlgren N, Yates JR, Mitani S, Carrington JC, Mello CC. Distinct argonaute-mediated 22G-RNA pathways direct genome surveillance in the C. elegans germline. Mol Cell. 2009 Oct 23; 36(2):231-44.
          View in: PubMed
        22. Batista PJ, Ruby JG, Claycomb JM, Chiang R, Fahlgren N, Kasschau KD, Chaves DA, Gu W, Vasale JJ, Duan S, Conte D, Luo S, Schroth GP, Carrington JC, Bartel DP, Mello CC. PRG-1 and 21U-RNAs interact to form the piRNA complex required for fertility in C. elegans. Mol Cell. 2008 Jul 11; 31(1):67-78.
          View in: PubMed
        23. Mello CC. Return to the RNAi world: rethinking gene expression and evolution. Cell Death Differ. 2007 Dec; 14(12):2013-20.
          View in: PubMed
        24. Mello CC. Return to the RNAi world: rethinking gene expression and evolution (Nobel Lecture). Angew Chem Int Ed Engl. 2007; 46(37):6985-94.
          View in: PubMed
        25. Yigit E, Batista PJ, Bei Y, Pang KM, Chen CC, Tolia NH, Joshua-Tor L, Mitani S, Simard MJ, Mello CC. Analysis of the C. elegans Argonaute family reveals that distinct Argonautes act sequentially during RNAi. Cell. 2006 Nov 17; 127(4):747-57.
          View in: PubMed
        26. Hayakawa A, Leonard D, Murphy S, Hayes S, Soto M, Fogarty K, Standley C, Bellve K, Lambright D, Mello C, Corvera S. The WD40 and FYVE domain containing protein 2 defines a class of early endosomes necessary for endocytosis. Proc Natl Acad Sci U S A. 2006 Aug 8; 103(32):11928-33.
          View in: PubMed
        27. Duchaine TF, Wohlschlegel JA, Kennedy S, Bei Y, Conte D, Pang K, Brownell DR, Harding S, Mitani S, Ruvkun G, Yates JR, Mello CC. Functional proteomics reveals the biochemical niche of C. elegans DCR-1 in multiple small-RNA-mediated pathways. Cell. 2006 Jan 27; 124(2):343-54.
          View in: PubMed
        28. Shirayama M, Soto MC, Ishidate T, Kim S, Nakamura K, Bei Y, van den Heuvel S, Mello CC. The Conserved Kinases CDK-1, GSK-3, KIN-19, and MBK-2 Promote OMA-1 Destruction to Regulate the Oocyte-to-Embryo Transition in C. elegans. Curr Biol. 2006 Jan 10; 16(1):47-55.
          View in: PubMed
        29. Nakamura K, Kim S, Ishidate T, Bei Y, Pang K, Shirayama M, Trzepacz C, Brownell DR, Mello CC. Wnt signaling drives WRM-1/beta-catenin asymmetries in early C. elegans embryos. Genes Dev. 2005 Aug 1; 19(15):1749-54.
          View in: PubMed
        30. Wang D, Kennedy S, Conte D, Kim JK, Gabel HW, Kamath RS, Mello CC, Ruvkun G. Somatic misexpression of germline P granules and enhanced RNA interference in retinoblastoma pathway mutants. Nature. 2005 Jul 28; 436(7050):593-7.
          View in: PubMed
        31. Chen CC, Simard MJ, Tabara H, Brownell DR, McCollough JA, Mello CC. A member of the polymerase beta nucleotidyltransferase superfamily is required for RNA interference in C. elegans. Curr Biol. 2005 Feb 22; 15(4):378-83.
          View in: PubMed
        32. Grigorenko AP, Moliaka YK, Soto MC, Mello CC, Rogaev EI. The Caenorhabditis elegans IMPAS gene, imp-2, is essential for development and is functionally distinct from related presenilins. Proc Natl Acad Sci U S A. 2004 Oct 12; 101(41):14955-60.
          View in: PubMed
        33. Mello CC, Conte D. Revealing the world of RNA interference. Nature. 2004 Sep 16; 431(7006):338-42.
          View in: PubMed
        34. Hutvágner G, Simard MJ, Mello CC, Zamore PD. Sequence-specific inhibition of small RNA function. PLoS Biol. 2004 Apr; 2(4):E98.
          View in: PubMed
        35. Pang KM, Ishidate T, Nakamura K, Shirayama M, Trzepacz C, Schubert CM, Priess JR, Mello CC. The minibrain kinase homolog, mbk-2, is required for spindle positioning and asymmetric cell division in early C. elegans embryos. Dev Biol. 2004 Jan 1; 265(1):127-39.
          View in: PubMed
        36. Venkatesan K, McManus HR, Mello CC, Smith TF, Hansen U. Functional conservation between members of an ancient duplicated transcription factor family, LSF/Grainyhead. Nucleic Acids Res. 2003 Aug 1; 31(15):4304-16.
          View in: PubMed
        37. Conte D, Mello CC. RNA interference in Caenorhabditis elegans. Curr Protoc Mol Biol. 2003 May; Chapter 26:Unit 26.3.
          View in: PubMed
        38. Unhavaithaya Y, Shin TH, Miliaras N, Lee J, Oyama T, Mello CC. MEP-1 and a homolog of the NURD complex component Mi-2 act together to maintain germline-soma distinctions in C. elegans. Cell. 2002 Dec 27; 111(7):991-1002.
          View in: PubMed
        39. Tabara H, Yigit E, Siomi H, Mello CC. The dsRNA binding protein RDE-4 interacts with RDE-1, DCR-1, and a DExH-box helicase to direct RNAi in C. elegans. Cell. 2002 Jun 28; 109(7):861-71.
          View in: PubMed
        40. Soto MC, Qadota H, Kasuya K, Inoue M, Tsuboi D, Mello CC, Kaibuchi K. The GEX-2 and GEX-3 proteins are required for tissue morphogenesis and cell migrations in C. elegans. Genes Dev. 2002 Mar 1; 16(5):620-32.
          View in: PubMed
        41. Grishok A, Mello CC. RNAi (Nematodes: Caenorhabditis elegans). Adv Genet. 2002; 46:339-60.
          View in: PubMed
        42. Grishok A, Pasquinelli AE, Conte D, Li N, Parrish S, Ha I, Baillie DL, Fire A, Ruvkun G, Mello CC. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell. 2001 Jul 13; 106(1):23-34.
          View in: PubMed
        43. Grishok A, Tabara H, Mello CC. Genetic requirements for inheritance of RNAi in C. elegans. Science. 2000 Mar 31; 287(5462):2494-7.
          View in: PubMed
        44. Tabara H, Sarkissian M, Kelly WG, Fleenor J, Grishok A, Timmons L, Fire A, Mello CC. The rde-1 gene, RNA interference, and transposon silencing in C. elegans. Cell. 1999 Oct 15; 99(2):123-32.
          View in: PubMed
        45. Shin TH, Yasuda J, Rocheleau CE, Lin R, Soto M, Bei Y, Davis RJ, Mello CC. MOM-4, a MAP kinase kinase kinase-related protein, activates WRM-1/LIT-1 kinase to transduce anterior/posterior polarity signals in C. elegans. Mol Cell. 1999 Aug; 4(2):275-80.
          View in: PubMed
        46. Rocheleau CE, Yasuda J, Shin TH, Lin R, Sawa H, Okano H, Priess JR, Davis RJ, Mello CC. WRM-1 activates the LIT-1 protein kinase to transduce anterior/posterior polarity signals in C. elegans. Cell. 1999 Jun 11; 97(6):717-26.
          View in: PubMed
        47. Tabara H, Grishok A, Mello CC. RNAi in C. elegans: soaking in the genome sequence. Science. 1998 Oct 16; 282(5388):430-1.
          View in: PubMed
        48. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998 Feb 19; 391(6669):806-11.
          View in: PubMed
        49. Rocheleau CE, Downs WD, Lin R, Wittmann C, Bei Y, Cha YH, Ali M, Priess JR, Mello CC. Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos. Cell. 1997 Aug 22; 90(4):707-16.
          View in: PubMed
        50. Mello C, Fire A. DNA transformation. Methods Cell Biol. 1995; 48:451-82.
          View in: PubMed
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