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    Greenfield Sluder PhD

    TitleProfessor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentCell and Developmental Biology
    AddressUniversity of Massachusetts Medical School
    377 Plantation Street
    Worcester MA 01605
    Phone508-856-8651
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentCell Biology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentProgram in Cell Dynamics

        Overview 
        Narrative

        Cell and Developmental Biology Department

        Sluder Lab Website

        Academic Background

        Kip Sluder received his A.B. from Middlebury College in 1968 andhis Ph.D. from the University of Pennsylvania in 1976. After an AmericanCancer Society post-doctoral fellowship with Dan Mazia at the Universityof California, Berkeley (1977 to 1980), he joined the faculty of the WorcesterFoundation for Experimental Biology in 1981. Since 1990, he has servedas co-director of the Analytical and Quantitative Light Microscopy Courseat the Marine Biological Laboratory, in Woods Hole Massachusetts.In 1997 Kip joined the Cell Biology Department at the University of MassachusettsMedical School as a Professor.

        Mitosis

        Our research is centered on the mechanisms that control various aspects of cell division. Applying microscopic and biophysical methods, we seek to elucidate the functional properties of control mechanisms as they operate in the living cell. Our results establish the basis for the integration of cell function with advances in the molecular biology of regulatory pathways. We use echinoderm zygotes, frog egg extracts, and cultured cells as model systems.

        One of the major projects in the laboratory seeks to elucidate the controls that ensure that the interphase centrosome reproduces, or doubles, only once in each cell cycle in proper coordination with nuclear events. We have recently shown that centrosome reproduction is coordinated with nuclear events by activities that function during S phase of the cell cycle.

        We have also developed the first Xenopus egg extract system that supports repeated rounds of centrosome reproduction in vitro. Using this system we have shown that the activity of the cyclin dependent kinase 2- cyclin E complex (Cdk2-cyclin E) is required for multiple rounds of centrosome duplication.

        ForRecent Images and Data, Please Visit our Lab Webpage:

        http://sluderlab.googlepages.com

        Figures

        Uetake and Sluder Figure 2

        Figure 1: Mammalian cells. (A and B) Overlaid phase and fluorescence images showing BrdU incorporation in mononucleate and binucleate cells. (A) Cells were previously treated with 0.5 µM cytochalasin D and cultured on bare glass. Mononucleate cells have incorporated BrdU, whereas the binucleates have not. (B) Cells treated with 0.5 µM cytochalasin D and cultured on fibronectin-coated glass. Both the mononucleate and binucleate cells have incorporated BrdU. (C) Cells previously treated with 0.5 µM cytochalasin D and cultured on fibronectin-coated glass (images taken from Video 4, available at http://www.jcb.org/cgi/content/full/jcb.200403014/DC1). Frames from a video sequence of two binucleate cells in the same field progressing through mitosis. The first to enter mitosis (top row) divides into two, whereas the second (bottom row) divides into three. Phase-contrast microscopy. Times are in h:min after cytochalasin D removal. Bars, 50 µm.

        Figure 1

        Figure 2: Repeated rounds of centrosome duplication in an aphidicolin-treated Xenopus egg extract. Frames from a time-lapse video sequence, showing the increase in aster number over time in a microscope field. The decrease in aster number in panel d is due to the migration of asters from the plane of focus and field of view. Minutes after addition of sperm nuclei are seen in the lower right corner of each frame. Polarization optics. 10 microns per scale division.

        In other studies we have characterized the cell cycle checkpoint controls for the metaphase-anaphase transition. These checkpoint pathways serve to ensure the equal distribution of chromosomes during cell division. We have demonstrated that signal transducing molecules in the kinetochore monitor chromosome attachment to the spindle and that even one unattached kinetochore will block the metaphase-anaphase transition.

        Using GFP-cyclin B and confocal microscopy we are also investigating how the checkpoint pathway that monitors the completion of DNA synthesis controls nuclear envelope breakdown and entry of the cell into mitosis.

        For more information, please visit our lab webpage:

        http://sluderlab.googlepages.com/



        Rotation Projects

        Potential Rotation Projects

        We favor having students work independently on defined projects that have promise of completion during the study period.

        Project #1: Use a frog egg extract that supports multiple rounds of centrosome duplication in vitro to investigate the role of various high interest kinases in the control of centrosome duplication. Also, we can use these extracts to further investigate how various other proteins interact with the centrosome to influence its duplication.

        Hinchcliffe, E.H., C. Li, E.A. Thompson, J.L. Maller and G. Sluder. 1999. Requirement of Cdk2-cyclin E activity for repeated centrosome reproduction in Xenopus egg extract. Science 283:851-854.

        Project #2: Use microsurgery and immunofluorescence on BSC-1 cells to further investigate how centrioles influence the interphase progression of the cell cycle.

        Hinchcliffe, E.H., F.J. Miller, M. Cham, A. Khodjakov and G. Sluder. 2001. Requirement of a centrosomal activity for cell cycle progression through G1 into S phase. Science 291: 1547-1550.



        Post Docs

        A postdoctoral position is available to study in this laboratory. Contact Dr. Sluder for additional details.

        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Sluder G. Centriole Engagement: It's Not Just Cohesin Any More. Curr Biol. 2013 Aug 5; 23(15):R659-60.
          View in: PubMed
        2. Sluder G, Wolf DE. Preface. Methods Cell Biol. 2013; 114:xix-xx.
          View in: PubMed
        3. Nordberg JJ, Sluder G. Practical aspects of adjusting digital cameras. Methods Cell Biol. 2013; 114:151-62.
          View in: PubMed
        4. Sluder G, Nordberg JJ. Microscope basics. Methods Cell Biol. 2013; 114:1-10.
          View in: PubMed
        5. Hatano T, Sluder G. The interrelationship between APC/C and Plk1 activities in centriole disengagement. Biol Open. 2012 Nov 15; 1(11):1153-60.
          View in: PubMed
        6. Krzywicka-Racka A, Sluder G. Repeated cleavage failure does not establish centrosome amplification in untransformed human cells. J Cell Biol. 2011 Jul 25; 194(2):199-207.
          View in: PubMed
        7. Sluder G, Khodjakov A. Centriole duplication: analogue control in a digital age. Cell Biol Int. 2010 Dec; 34(12):1239-45.
          View in: PubMed
        8. Uetake Y, Sluder G. Prolonged prometaphase blocks daughter cell proliferation despite normal completion of mitosis. Curr Biol. 2010 Sep 28; 20(18):1666-71.
          View in: PubMed
        9. Heilman SA, Nordberg JJ, Liu Y, Sluder G, Chen JJ. Abrogation of the postmitotic checkpoint contributes to polyploidization in human papillomavirus E7-expressing cells. J Virol. 2009 Mar; 83(6):2756-64.
          View in: PubMed
        10. Schnackenberg BJ, Marzluff WF, Sluder G. Cyclin E in centrosome duplication and reduplication in sea urchin zygotes. J Cell Physiol. 2008 Dec; 217(3):626-31.
          View in: PubMed
        11. Matijasevic Z, Krzywicka-Racka A, Sluder G, Jones SN. MdmX regulates transformation and chromosomal stability in p53-deficient cells. Cell Cycle. 2008 Oct; 7(19):2967-73.
          View in: PubMed
        12. Uetake Y, Sluder G. Cell-cycle progression without an intact microtuble cytoskeleton. Curr Biol. 2007 Dec 4; 17(23):2081-6.
          View in: PubMed
        13. Loncarek J, Sluder G, Khodjakov A. Centriole biogenesis: a tale of two pathways. Nat Cell Biol. 2007 Jul; 9(7):736-8.
          View in: PubMed
        14. Liu Y, Heilman SA, Illanes D, Sluder G, Chen JJ. p53-independent abrogation of a postmitotic checkpoint contributes to human papillomavirus E6-induced polyploidy. Cancer Res. 2007 Mar 15; 67(6):2603-10.
          View in: PubMed
        15. Uetake Y, Loncarek J, Nordberg JJ, English CN, La Terra S, Khodjakov A, Sluder G. Cell cycle progression and de novo centriole assembly after centrosomal removal in untransformed human cells. J Cell Biol. 2007 Jan 15; 176(2):173-82.
          View in: PubMed
        16. Sluder G, Nordberg JJ. Microscope basics. Methods Cell Biol. 2007; 81:1-10.
          View in: PubMed
        17. Nordberg JJ, Sluder G. Practical aspects of adjusting digital cameras. Methods Cell Biol. 2007; 81:159-69.
          View in: PubMed
        18. Sluder G, Nordberg JJ, Miller FJ, Hinchcliffe EH. A sealed preparation for long-term observations of cultured cells. CSH Protoc. 2007; 2007:pdb.prot4660.
          View in: PubMed
        19. Sluder G, Nordberg JJ, Miller FJ, Hinchcliffe EH. A sealed preparation for long-term observations of cultured cells: details of support slide construction. CSH Protoc. 2007; 2007:pdb.ip26.
          View in: PubMed
        20. Hinchcliffe EH, Sluder G. Working with classic video. Methods Cell Biol. 2007; 81:141-57.
          View in: PubMed
        21. Ehrhardt AG, Sluder G. Spindle pole fragmentation due to proteasome inhibition. J Cell Physiol. 2005 Sep; 204(3):808-18.
          View in: PubMed
        22. Sluder G. Two-way traffic: centrosomes and the cell cycle. Nat Rev Mol Cell Biol. 2005 Sep; 6(9):743-8.
          View in: PubMed
        23. La Terra S, English CN, Hergert P, McEwen BF, Sluder G, Khodjakov A. The de novo centriole assembly pathway in HeLa cells: cell cycle progression and centriole assembly/maturation. J Cell Biol. 2005 Feb 28; 168(5):713-22.
          View in: PubMed
        24. Murata-Hori M, Sluder G, Wang YL. Regulation of cell cycle by the anaphase spindle midzone. BMC Cell Biol. 2004 Dec 23; 5(1):49.
          View in: PubMed
        25. Uetake Y, Sluder G. Cell cycle progression after cleavage failure: mammalian somatic cells do not possess a "tetraploidy checkpoint". J Cell Biol. 2004 Jun 7; 165(5):609-15.
          View in: PubMed
        26. Sluder G, Nordberg JJ. The good, the bad and the ugly: the practical consequences of centrosome amplification. Curr Opin Cell Biol. 2004 Feb; 16(1):49-54.
          View in: PubMed
        27. Sluder G, Nordberg JJ. Microscope basics. Methods Cell Biol. 2003; 72:1-10.
          View in: PubMed
        28. Hinchcliffe EH, Sluder G. "Do not (mis-)adjust your set": maintaining specimen detail in the video microscope. Methods Cell Biol. 2003; 72:65-85.
          View in: PubMed
        29. Khodjakov A, Rieder CL, Sluder G, Cassels G, Sibon O, Wang CL. De novo formation of centrosomes in vertebrate cells arrested during S phase. J Cell Biol. 2002 Sep 30; 158(7):1171-81.
          View in: PubMed
        30. Hinchcliffe EH, Sluder G. Two for two: Cdk2 and its role in centrosome doubling. Oncogene. 2002 Sep 9; 21(40):6154-60.
          View in: PubMed
        31. Hinchcliffe EH, Sluder G. Centrosome duplication: three kinases come up a winner! Curr Biol. 2001 Sep 4; 11(17):R698-701.
          View in: PubMed
        32. Hinchcliffe EH, Sluder G. "It takes two to tango": understanding how centrosome duplication is regulated throughout the cell cycle. Genes Dev. 2001 May 15; 15(10):1167-81.
          View in: PubMed
        33. Hinchcliffe EH, Miller FJ, Cham M, Khodjakov A, Sluder G. Requirement of a centrosomal activity for cell cycle progression through G1 into S phase. Science. 2001 Feb 23; 291(5508):1547-50.
          View in: PubMed
        34. Hinchcliffe EH, Sluder G. Centrosome reproduction in Xenopus lysates. Methods Cell Biol. 2001; 67:269-87.
          View in: PubMed
        35. Palmieri SJ, Nebl T, Pope RK, Seastone DJ, Lee E, Hinchcliffe EH, Sluder G, Knecht D, Cardelli J, Luna EJ. Mutant Rac1B expression in Dictyostelium: effects on morphology, growth, endocytosis, development, and the actin cytoskeleton. Cell Motil Cytoskeleton. 2000 Aug; 46(4):285-304.
          View in: PubMed
        36. Suprynowicz FA, Groigno L, Whitaker M, Miller FJ, Sluder G, Sturrock J, Whalley T. Activation of protein kinase C alters p34(cdc2) phosphorylation state and kinase activity in early sea urchin embryos by abolishing intracellular Ca2+ transients. Biochem J. 2000 Jul 15; 349(Pt 2):489-99.
          View in: PubMed
        37. Sluder G, McCollum D. Molecular biology. The mad ways of meiosis. Science. 2000 Jul 14; 289(5477):254-5.
          View in: PubMed
        38. Sluder G, Hinchcliffe EH. The coordination of centrosome reproduction with nuclear events during the cell cycle. Curr Top Dev Biol. 2000; 49:267-89.
          View in: PubMed
        39. Sluder G, Hinchcliffe EH. Control of centrosome reproduction: the right number at the right time. Biol Cell. 1999 Jul; 91(6):413-27.
          View in: PubMed
        40. Hinchcliffe EH, Thompson EA, Miller FJ, Yang J, Sluder G. Nucleo-cytoplasmic interactions that control nuclear envelope breakdown and entry into mitosis in the sea urchin zygote. J Cell Sci. 1999 Apr; 112 ( Pt 8):1139-48.
          View in: PubMed
        41. Hinchcliffe EH, Li C, Thompson EA, Maller JL, Sluder G. Requirement of Cdk2-cyclin E activity for repeated centrosome reproduction in Xenopus egg extracts. Science. 1999 Feb 5; 283(5403):851-4.
          View in: PubMed
        42. Sluder G, Miller FJ, Hinchcliffe EH. Using sea urchin gametes for the study of mitosis. Methods Cell Biol. 1999; 61:439-72.
          View in: PubMed
        43. Hinchcliffe EH, Cassels GO, Rieder CL, Sluder G. The coordination of centrosome reproduction with nuclear events of the cell cycle in the sea urchin zygote. J Cell Biol. 1998 Mar 23; 140(6):1417-26.
          View in: PubMed
        44. Sluder G, Hinchcliffe EH. Video basics: use of camera and monitor adjustments. Methods Cell Biol. 1998; 56:1-17.
          View in: PubMed
        45. Sluder G, Hinchcliffe EH. The apparent linkage between centriole replication and the S phase of the cell cycle. Cell Biol Int. 1998; 22(1):3-5.
          View in: PubMed
        46. Wheatley SP, Hinchcliffe EH, Glotzer M, Hyman AA, Sluder G, Wang Y. CDK1 inactivation regulates anaphase spindle dynamics and cytokinesis in vivo. J Cell Biol. 1997 Jul 28; 138(2):385-93.
          View in: PubMed
        47. Rieder CL, Khodjakov A, Paliulis LV, Fortier TM, Cole RW, Sluder G. Mitosis in vertebrate somatic cells with two spindles: implications for the metaphase/anaphase transition checkpoint and cleavage. Proc Natl Acad Sci U S A. 1997 May 13; 94(10):5107-12.
          View in: PubMed
        48. Sluder G, Thompson EA, Miller FJ, Hayes J, Rieder CL. The checkpoint control for anaphase onset does not monitor excess numbers of spindle poles or bipolar spindle symmetry. J Cell Sci. 1997 Feb; 110 ( Pt 4):421-9.
          View in: PubMed
        49. Sluder G, Rieder CL. Controls for centrosome reproduction in animal cells: issues and recent observations. Cell Motil Cytoskeleton. 1996; 33(1):1-5.
          View in: PubMed
        50. Rieder CL, Cole RW, Khodjakov A, Sluder G. The checkpoint delaying anaphase in response to chromosome monoorientation is mediated by an inhibitory signal produced by unattached kinetochores. J Cell Biol. 1995 Aug; 130(4):941-8.
          View in: PubMed
        51. Sluder G, Thompson EA, Rieder CL, Miller FJ. Nuclear envelope breakdown is under nuclear not cytoplasmic control in sea urchin zygotes. J Cell Biol. 1995 Jun; 129(6):1447-58.
          View in: PubMed
        52. Rieder CL, Schultz A, Cole R, Sluder G. Anaphase onset in vertebrate somatic cells is controlled by a checkpoint that monitors sister kinetochore attachment to the spindle. J Cell Biol. 1994 Dec; 127(5):1301-10.
          View in: PubMed
        53. Sluder G, Miller FJ, Thompson EA, Wolf DE. Feedback control of the metaphase-anaphase transition in sea urchin zygotes: role of maloriented chromosomes. J Cell Biol. 1994 Jul; 126(1):189-98.
          View in: PubMed
        54. Sluder G, Miller FJ, Lewis K. Centrosome inheritance in starfish zygotes. II: Selective suppression of the maternal centrosome during meiosis. Dev Biol. 1993 Jan; 155(1):58-67.
          View in: PubMed
        55. Sluder G. Double or nothing. Curr Biol. 1992 May; 2(5):243-5.
          View in: PubMed
        56. Melan MA, Sluder G. Redistribution and differential extraction of soluble proteins in permeabilized cultured cells. Implications for immunofluorescence microscopy. J Cell Sci. 1992 Apr; 101 ( Pt 4):731-43.
          View in: PubMed
        57. Sluder G, Miller FJ, Cole R, Rieder CL. Protein synthesis and the cell cycle: centrosome reproduction in sea urchin eggs is not under translational control. J Cell Biol. 1990 Jun; 110(6):2025-32.
          View in: PubMed
        58. Sluder G. Functional properties of kinetochores in animal cells. Curr Opin Cell Biol. 1990 Feb; 2(1):23-7.
          View in: PubMed
        59. Sluder G, Miller FJ, Lewis K, Davison ED, Rieder CL. Centrosome inheritance in starfish zygotes: selective loss of the maternal centrosome after fertilization. Dev Biol. 1989 Feb; 131(2):567-79.
          View in: PubMed
        60. Sluder G. Centrosomes and the cell cycle. J Cell Sci Suppl. 1989; 12:253-75.
          View in: PubMed
        61. Sluder G, Miller FJ, Rieder CL. Reproductive capacity of sea urchin centrosomes without centrioles. Cell Motil Cytoskeleton. 1989; 13(4):264-73.
          View in: PubMed
        62. Sluder G, Lewis K. Relationship between nuclear DNA synthesis and centrosome reproduction in sea urchin eggs. J Exp Zool. 1987 Oct; 244(1):89-100.
          View in: PubMed
        63. Sluder G, Miller FJ, Rieder CL. The reproduction of centrosomes: nuclear versus cytoplasmic controls. J Cell Biol. 1986 Nov; 103(5):1873-81.
          View in: PubMed
        64. Sluder G, Miller FJ, Spanjian K. The role of spindle microtubules in the timing of the cell cycle in echinoderm eggs. J Exp Zool. 1986 Jun; 238(3):325-36.
          View in: PubMed
        65. Sluder G, Miller FJ, Rieder CL. Centrosomes are required for the assembly of a bipolar spindle in animal cells. Ann N Y Acad Sci. 1986; 466:669-73.
          View in: PubMed
        66. Sluder G, Begg DA. Experimental analysis of the reproduction of spindle poles. J Cell Sci. 1985 Jun; 76:35-51.
          View in: PubMed
        67. Sluder G, Rieder CL. Experimental separation of pronuclei in fertilized sea urchin eggs: chromosomes do not organize a spindle in the absence of centrosomes. J Cell Biol. 1985 Mar; 100(3):897-903.
          View in: PubMed
        68. Sluder G, Rieder CL. Centriole number and the reproductive capacity of spindle poles. J Cell Biol. 1985 Mar; 100(3):887-96.
          View in: PubMed
        69. Sluder G, Begg DA. Control mechanisms of the cell cycle: role of the spatial arrangement of spindle components in the timing of mitotic events. J Cell Biol. 1983 Sep; 97(3):877-86.
          View in: PubMed
        70. Mazia D, Paweletz N, Sluder G, Finze EM. Cooperation of kinetochores and pole in the establishment of monopolar mitotic apparatus. Proc Natl Acad Sci U S A. 1981 Jan; 78(1):377-81.
          View in: PubMed
        71. Sluder G. Role of spindle microtubules in the control of cell cycle timing. J Cell Biol. 1979 Mar; 80(3):674-91.
          View in: PubMed
        72. Sluder G. Experimental manipulation of the amount of tubulin available for assembly into the spindle of dividing sea urchin eggs. J Cell Biol. 1976 Jul; 70(1):75-85.
          View in: PubMed
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