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    Dannel McCollum PhD

    TitleProfessor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentBiochemistry and Molecular Pharmacology
    AddressUniversity of Massachusetts Medical School
    364 Plantation Street
    Worcester MA 01605
    Phone508-856-8767
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMD/PhD Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMolecular Genetics and Microbiology

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentProgram in Cell Dynamics

        Overview 
        Narrative

        Academic Background

        Dan McCollum received his B.S. in Biochemistry from the University of Illinois in 1987, and his Ph.D., from the University of California at San Diego in 1993.  He did his postdoctoral training in Dr. Kathleen Gould's lab at Vanderbilt University.  Dr. McCollum joined the faculty at the Worcester Foundation for Biomedical Research in 1996, and then joined the University of Massachusetts Medical School in 1997.  Dr. McCollum is a member of the Department of Biochemistry and Molecular Pharmacology and the Program in Cell Dynamics.

        Molecular Mechanisms which Regulate Cytokinesis

        Photo: Dannel McCollum, PhD

        The primary interest of my lab is understanding the molecular mechanisms which coordinate mitosis with cell division (cytokinesis).  Proper regulation of cytokinesis is critical for a number of reasons.  Normally cytokinesis is tightly coupled to the completion of mitosis.  If cells either loose this coupling, or have defects in cytokinesis, genetic instability can result, often leading to genetic defects and cancer.  We have chosen the fission yeast, Schizosaccharomyces pombe, as a model system for these studies because of the powerful molecular genetics available in S. pombe and the fact that the mechanisms of cytokinesis and cell cycle control are highly conserved between S. pombe and higher eukaryotic cells.

        Through the combined use of genetic biochemical and cytological techniques, we have identified a novel signal transduction pathway which functions to coordinate cell division and mitosis.  This pathway (the SIN pathway) includes 4 protein kinases and one small GTPase, and functions to transmit a signal from the spindle poles to the cell division site causing initiation of cell division.  Recent studies have characterized the order of function of the proteins in the pathway and revealed key mechanisms by which signaling through the pathway is regulated to ensure that cytokinesis is coupled to the other events of mitosis.  For example, we recently showed that the Dma1 protein is required to inhibit the SIN in response to mitotic spindle defects to ensure that cytokinesis does not take place when chromosomes are unable to be segregated.  Interestingly a human homolog of Dma1 (CHFR) is deleted in a large percent of tumors suggesting that regulation of an analogous pathway may be important to inhibit tumor formation.

        Research Figure


        Rotation Projects

        Rotation Projects

        Little is known about how the SID pathway monitors mitosis to ensure that cytokinesis is not initiated until mitosis is complete. We have begun to examine the function of homologs of the SID pathway genes in animal cells using RNA interference (RNAi) to disrupt their function. A potential project, would be to disrupt the function of one of the SID pathway genes and characterize its function in animal cells. We have also carried out a genetic suppressor screen to identify potential inhibitors of the SID pathway, and another potential project would be to characterize and clone one of these SID pathway inhibitory genes. A new project in the lab has involved characterization of a highly conserved protein phosphatase, which we have shown is required to inhibit progression into the next cell cycle if cytokinesis is incomplete. One project could involve examination of how this phosphatase inhibits cell cycle progression using biochemical and cytological approaches.



        Post Docs

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

        Bibliographic 
        selected publications
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        1. Bajpai A, Feoktistova A, Chen JS, McCollum D, Sato M, Carazo-Salas RE, Gould KL, Csikász-Nagy A. Dynamics of SIN Asymmetry Establishment. PLoS Comput Biol. 2013 Jul; 9(7):e1003147.
          View in: PubMed
        2. Cipak L, Gupta S, Rajovic I, Jin QW, Anrather D, Ammerer G, McCollum D, Gregan J. Crosstalk between casein kinase II and Ste20-related kinase Nak1. Cell Cycle. 2013 Mar 15; 12(6):884-8.
          View in: PubMed
        3. Gupta S, Mana-Capelli S, McLean JR, Chen CT, Ray S, Gould KL, McCollum D. Identification of SIN Pathway Targets Reveals Mechanisms of Crosstalk between NDR Kinase Pathways. Curr Biol. 2013 Feb 18; 23(4):333-8.
          View in: PubMed
        4. McCollum D. Monopolin. Curr Biol. 2012 Nov 20; 22(22):R937-8.
          View in: PubMed
        5. Mana-Capelli S, McLean JR, Chen CT, Gould KL, McCollum D. The kinesin-14 Klp2 is negatively regulated by the SIN for proper spindle elongation and telophase nuclear positioning. Mol Biol Cell. 2012 Dec; 23(23):4592-600.
          View in: PubMed
        6. Wang Y, Li WZ, Johnson AE, Luo ZQ, Sun XL, Feoktistova A, McDonald WH, McLeod I, Yates JR, Gould KL, McCollum D, Jin QW. Dnt1 acts as a mitotic inhibitor of the spindle checkpoint protein dma1 in fission yeast. Mol Biol Cell. 2012 Sep; 23(17):3348-56.
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        7. Johnson AE, McCollum D, Gould KL. Polar opposites: Fine-tuning cytokinesis through SIN asymmetry. Cytoskeleton (Hoboken). 2012 Oct; 69(10):686-99.
          View in: PubMed
        8. Ma H, McLean JR, Chao LF, Mana-Capelli S, Paramasivam M, Hagstrom KA, Gould KL, McCollum D. A highly efficient multifunctional tandem affinity purification approach applicable to diverse organisms. Mol Cell Proteomics. 2012 Aug; 11(8):501-11.
          View in: PubMed
        9. Rentas S, Saberianfar R, Grewal C, Kanippayoor R, Mishra M, McCollum D, Karagiannis J. The SET Domain Protein, Set3p, Promotes the Reliable Execution of Cytokinesis in Schizosaccharomyces pombe. PLoS One. 2012; 7(2):e31224.
          View in: PubMed
        10. Choi SH, McCollum D. A role for metaphase spindle elongation forces in correction of merotelic kinetochore attachments. Curr Biol. 2012 Feb 7; 22(3):225-30.
          View in: PubMed
        11. Gupta S, McCollum D. Crosstalk between NDR kinase pathways coordinates cell cycle dependent actin rearrangements. Cell Div. 2011; 6:19.
          View in: PubMed
        12. Paramasivam M, Sarkeshik A, Yates JR, Fernandes MJ, McCollum D. Angiomotin family proteins are novel activators of the LATS2 kinase tumor suppressor. Mol Biol Cell. 2011 Oct; 22(19):3725-33.
          View in: PubMed
        13. McCollum D. Prevention of merotelic chromosome attachments by the monopolin complex. Cell Cycle. 2010 Nov; 9(21):4258.
          View in: PubMed
        14. Ray S, Kume K, Gupta S, Ge W, Balasubramanian M, Hirata D, McCollum D. The mitosis-to-interphase transition is coordinated by cross talk between the SIN and MOR pathways in Schizosaccharomyces pombe. J Cell Biol. 2010 Sep 6; 190(5):793-805.
          View in: PubMed
        15. McCollum D. Cytokinesis: ER keeps Mid1 in the middle. Curr Biol. 2010 Jun 8; 20(11):R484-6.
          View in: PubMed
        16. García-Cortés JC, McCollum D. Proper timing of cytokinesis is regulated by Schizosaccharomyces pombe Etd1. J Cell Biol. 2009 Sep 7; 186(5):739-53.
          View in: PubMed
        17. Choi SH, Péli-Gulli MP, Mcleod I, Sarkeshik A, Yates JR, Simanis V, McCollum D. Phosphorylation state defines discrete roles for monopolin in chromosome attachment and spindle elongation. Curr Biol. 2009 Jun 23; 19(12):985-95.
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        18. Chen CT, Feoktistova A, Chen JS, Shim YS, Clifford DM, Gould KL, McCollum D. The SIN kinase Sid2 regulates cytoplasmic retention of the S. pombe Cdc14-like phosphatase Clp1. Curr Biol. 2008 Oct 28; 18(20):1594-9.
          View in: PubMed
        19. Yan H, Ge W, Chew TG, Chow JY, McCollum D, Neiman AM, Balasubramanian MK. The meiosis-specific Sid2p-related protein Slk1p regulates forespore membrane assembly in fission yeast. Mol Biol Cell. 2008 Sep; 19(9):3676-90.
          View in: PubMed
        20. Clifford DM, Chen CT, Roberts RH, Feoktistova A, Wolfe BA, Chen JS, McCollum D, Gould KL. The role of Cdc14 phosphatases in the control of cell division. Biochem Soc Trans. 2008 Jun; 36(Pt 3):436-8.
          View in: PubMed
        21. Jin QW, Ray S, Choi SH, McCollum D. The nucleolar Net1/Cfi1-related protein Dnt1 antagonizes the septation initiation network in fission yeast. Mol Biol Cell. 2007 Aug; 18(8):2924-34.
          View in: PubMed
        22. Chen CT, Peli-Gulli MP, Simanis V, McCollum D. S. pombe FEAR protein orthologs are not required for release of Clp1/Flp1 phosphatase from the nucleolus during mitosis. J Cell Sci. 2006 Nov 1; 119(Pt 21):4462-6.
          View in: PubMed
        23. Jin QW, Zhou M, Bimbo A, Balasubramanian MK, McCollum D. A role for the septation initiation network in septum assembly revealed by genetic analysis of sid2-250 suppressors. Genetics. 2006 Apr; 172(4):2101-12.
          View in: PubMed
        24. McCollum D. Cytokinesis: breaking the ties that bind. Curr Biol. 2005 Dec 20; 15(24):R998-1000.
          View in: PubMed
        25. Trautmann S, McCollum D. Distinct nuclear and cytoplasmic functions of the S. pombe Cdc14-like phosphatase Clp1p/Flp1p and a role for nuclear shuttling in its regulation. Curr Biol. 2005 Aug 9; 15(15):1384-9.
          View in: PubMed
        26. Doxsey S, McCollum D, Theurkauf W. Centrosomes in cellular regulation. Annu Rev Cell Dev Biol. 2005; 21:411-34.
          View in: PubMed
        27. McCollum D. Cytokinesis: the central spindle takes center stage. Curr Biol. 2004 Nov 23; 14(22):R953-5.
          View in: PubMed
        28. Trautmann S, Rajagopalan S, McCollum D. The S. pombe Cdc14-like phosphatase Clp1p regulates chromosome biorientation and interacts with Aurora kinase. Dev Cell. 2004 Nov; 7(5):755-62.
          View in: PubMed
        29. Mishra M, Karagiannis J, Trautmann S, Wang H, McCollum D, Balasubramanian MK. The Clp1p/Flp1p phosphatase ensures completion of cytokinesis in response to minor perturbation of the cell division machinery in Schizosaccharomyces pombe. J Cell Sci. 2004 Aug 1; 117(Pt 17):3897-910.
          View in: PubMed
        30. Mitra P, Zhang Y, Rameh LE, Ivshina MP, McCollum D, Nunnari JJ, Hendricks GM, Kerr ML, Field SJ, Cantley LC, Ross AH. A novel phosphatidylinositol(3,4,5)P3 pathway in fission yeast. J Cell Biol. 2004 Jul 19; 166(2):205-11.
          View in: PubMed
        31. Hou MC, Guertin DA, McCollum D. Initiation of cytokinesis is controlled through multiple modes of regulation of the Sid2p-Mob1p kinase complex. Mol Cell Biol. 2004 Apr; 24(8):3262-76.
          View in: PubMed
        32. Jin QW, McCollum D. Scw1p antagonizes the septation initiation network to regulate septum formation and cell separation in the fission yeast Schizosaccharomyces pombe. Eukaryot Cell. 2003 Jun; 2(3):510-20.
          View in: PubMed
        33. Hou MC, Wiley DJ, Verde F, McCollum D. Mob2p interacts with the protein kinase Orb6p to promote coordination of cell polarity with cell cycle progression. J Cell Sci. 2003 Jan 1; 116(Pt 1):125-35.
          View in: PubMed
        34. Guertin DA, Venkatram S, Gould KL, McCollum D. Dma1 prevents mitotic exit and cytokinesis by inhibiting the septation initiation network (SIN). Dev Cell. 2002 Dec; 3(6):779-90.
          View in: PubMed
        35. Trautmann S, McCollum D. Cell cycle: new functions for Cdc14 family phosphatases. Curr Biol. 2002 Oct 29; 12(21):R733-5.
          View in: PubMed
        36. McCollum D. First things first: spindle orientation and mitotic progression. Nat Cell Biol. 2002 Oct; 4(10):E225-6.
          View in: PubMed
        37. Guertin DA, Trautmann S, McCollum D. Cytokinesis in eukaryotes. Microbiol Mol Biol Rev. 2002 Jun; 66(2):155-78.
          View in: PubMed
        38. Hou MC, McCollum D. Cytokinesis: myosin spots the ring. Curr Biol. 2002 Apr 30; 12(9):R334-6.
          View in: PubMed
        39. Wang H, Tang X, Liu J, Trautmann S, Balasundaram D, McCollum D, Balasubramanian MK. The multiprotein exocyst complex is essential for cell separation in Schizosaccharomyces pombe. Mol Biol Cell. 2002 Feb; 13(2):515-29.
          View in: PubMed
        40. Trautmann S, Wolfe BA, Jorgensen P, Tyers M, Gould KL, McCollum D. Fission yeast Clp1p phosphatase regulates G2/M transition and coordination of cytokinesis with cell cycle progression. Curr Biol. 2001 Jun 26; 11(12):931-40.
          View in: PubMed
        41. Guertin DA, McCollum D. Interaction between the noncatalytic region of Sid1p kinase and Cdc14p is required for full catalytic activity and localization of Sid1p. J Biol Chem. 2001 Jul 27; 276(30):28185-9.
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        42. McCollum D, Gould KL. Timing is everything: regulation of mitotic exit and cytokinesis by the MEN and SIN. Trends Cell Biol. 2001 Feb; 11(2):89-95.
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        43. Sluder G, McCollum D. Molecular biology. The mad ways of meiosis. Science. 2000 Jul 14; 289(5477):254-5.
          View in: PubMed
        44. Hou MC, Salek J, McCollum D. Mob1p interacts with the Sid2p kinase and is required for cytokinesis in fission yeast. Curr Biol. 2000 May 18; 10(10):619-22.
          View in: PubMed
        45. Guertin DA, Chang L, Irshad F, Gould KL, McCollum D. The role of the sid1p kinase and cdc14p in regulating the onset of cytokinesis in fission yeast. EMBO J. 2000 Apr 17; 19(8):1803-15.
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        46. Sparks CA, Morphew M, McCollum D. Sid2p, a spindle pole body kinase that regulates the onset of cytokinesis. J Cell Biol. 1999 Aug 23; 146(4):777-90.
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        47. McCollum D, Balasubramanian M, Gould K. Identification of cold-sensitive mutations in the Schizosaccharomyces pombe actin locus. FEBS Lett. 1999 May 28; 451(3):321-6.
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        48. Bähler J, Steever AB, Wheatley S, Wang Y, Pringle JR, Gould KL, McCollum D. Role of polo kinase and Mid1p in determining the site of cell division in fission yeast. J Cell Biol. 1998 Dec 14; 143(6):1603-16.
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