Photo of David S. Pellman,  MD

David S. Pellman, MD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-4918
Fax: (617) 632-6845


david_pellman@dfci.harvard.edu

David S. Pellman, MD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Margaret M. Dyson Professor of Pediatric Oncology, Pediatrics, Harvard Medical School
  • Professor, Cell Biology, Harvard Medical School
  • Principal Investigator, Pediatric Oncology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

DF/HCC ASSOCIATIONS

  • Member, Center Scientific Council

Research Abstract

Our laboratory is interested in how cell cycle signals regulate chromosome segregation and polarized morphogenesis. Our experimental approaches include a combination of biochemical, genetic and live-cell imaging. There are ongoing projects using both yeast and animal cell systems.

One area of interest for the laboratory is the mechanism of anaphase B. Many of the proteins involved in anaphase have been identified through genetic screens. One conserved component of the central spindle identified in our laboratory has been purified and its in vitro properties are being characterized. The goal of this work is to understand how the half spindles are held together and how the spindle is disassembled at the end of mitosis. A related project concerns the regulation of spindle function by the cyclin degradation machinery (anaphase promoting complex or APC). Several spindle proteins are degraded through the APC at different times during the cell cycle. We are working on the mechanisms regulating the timing of these degradation events.

A second area of interest is how polarity factors determine the position of the spindle within the cell. Spindle position is regulated during the development of many organisms in order to generate asymmetric cell divisions. Establishing spindle position involves capture of astral microtubules by poorly defined cortical proteins. Through genetic screens we have identified cortical cytoskeletal proteins and G-protein regulators necessary for determining spindle position. We hope to develop a mechanistic understanding of this process by studying the biochemical interactions between these proteins. In addition, a recently described cell cycle checkpoint monitors the successful positioning of the spindle in yeast. Work is in progress to define how the cell recognizes abnormal spindle position and communicates this information to cell cycle regulators.

Publications

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  • Selmecki AM, Maruvka YE, Richmond PA, Guillet M, Shoresh N, Sorenson AL, De S, Kishony R, Michor F, Dowell R, Pellman D. Polyploidy can drive rapid adaptation in yeast. Nature 2015; 519:349-52. PubMed
  • Godinho SA, Picone R, Burute M, Dagher R, Su Y, Leung CT, Polyak K, Brugge JS, Théry M, Pellman D. Oncogene-like induction of cellular invasion from centrosome amplification. Nature 2014. PubMed
  • Lane AA, Chapuy B, Lin CY, Tivey T, Li H, Townsend EC, van Bodegom D, Day TA, Wu SC, Liu H, Yoda A, Alexe G, Schinzel AC, Sullivan TJ, Malinge S, Taylor JE, Stegmaier K, Jaffe JD, Bustin M, te Kronnie G, Izraeli S, Harris MH, Stevenson KE, Neuberg D, Silverman LB, Sallan SE, Bradner JE, Hahn WC, Crispino JD, Pellman D, Weinstock DM. Triplication of a 21q22 region contributes to B cell transformation through HMGN1 overexpression and loss of histone H3 Lys27 trimethylation. Nat Genet 2014. PubMed
  • Lee DH, Acharya SS, Kwon M, Drane P, Guan Y, Adelmant G, Kalev P, Shah J, Pellman D, Marto JA, Chowdhury D. Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks. Mol Cell 2014. PubMed
  • Su X, Arellano-Santoyo H, Portran D, Gaillard J, Vantard M, Thery M, Pellman D. Microtubule-sliding activity of a kinesin-8 promotes spindle assembly and spindle-length control. Nat Cell Biol 2013; 15:948-57. PubMed
  • Atkins BD, Yoshida S, Saito K, Wu CF, Lew DJ, Pellman D. Inhibition of Cdc42 during mitotic exit is required for cytokinesis. J Cell Biol 2013; 202:231-40. PubMed
  • Su X, Ohi R, Pellman D. Move in for the kill: motile microtubule regulators. Trends Cell Biol 2012; 22:567-75. PubMed
  • Buttery SM, Kono K, Stokasimov E, Pellman D. Regulation of the formin Bnr1 by septins anda MARK/Par1-family septin-associated kinase. Mol Biol Cell 2012; 23:4041-53. PubMed
  • Kono K, Saeki Y, Yoshida S, Tanaka K, Pellman D. Proteasomal degradation resolves competition between cell polarization and cellular wound healing. Cell 2012; 150:151-64. PubMed
  • Varetti G, Pellman D. "Two" much of a good thing: telomere damage-induced genome doubling drives tumorigenesis. Cancer Cell 2012; 21:712-4. PubMed
  • Carter SL, Cibulskis K, Helman E, McKenna A, Shen H, Zack T, Laird PW, Onofrio RC, Winckler W, Weir BA, Beroukhim R, Pellman D, Levine DA, Lander ES, Meyerson M, Getz G. Absolute quantification of somatic DNA alterations in human cancer. Nat Biotechnol 2012; 30:413-21. PubMed
  • Storchová Z, Becker J, Talarek N, Kögelsberger S, Pellman D. Bub1, Sgo1 and Mps1 mediate a distinct pathway for chromosome bi-orientation in budding yeast. Mol Biol Cell 2011. PubMed
  • Meyerson M, Pellman D. Cancer genomes evolve by pulverizing single chromosomes. Cell 2011; 144:9-10. PubMed
  • Breuer M, Kolano A, Kwon M, Li CC, Tsai TF, Pellman D, Brunet S, Verlhac MH. HURP permits MTOC sorting for robust meiotic spindle bipolarity, similar to extra centrosome clustering in cancer cells. J Cell Biol 2010; 191:1251-60. PubMed
  • Vinciguerra P, Godinho SA, Parmar K, Pellman D, D'Andrea AD. Cytokinesis failure occurs in Fanconi anemia pathway-deficient murine and human bone marrow hematopoietic cells. J Clin Invest 2010; 120:3834-42. PubMed
  • Pellman D. David Pellman: Grasping the geometry of cancer. [Interviewed by Caitlin Sedwick]. J Cell Biol 2010; 190:4-5. PubMed
  • Kwiatkowski N, Jelluma N, Filippakopoulos P, Soundararajan M, Manak MS, Kwon M, Choi HG, Sim T, Deveraux QL, Rottmann S, Pellman D, Shah JV, Kops GJ, Knapp S, Gray NS. Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function. Nat Chem Biol 2010; 6:359-68. PubMed
  • Tischfield MA, Baris HN, Wu C, Rudolph G, Van Maldergem L, He W, Chan WM, Andrews C, Demer JL, Robertson RL, Mackey DA, Ruddle JB, Bird TD, Gottlob I, Pieh C, Traboulsi EI, Pomeroy SL, Hunter DG, Soul JS, Newlin A, Sabol LJ, Doherty EJ, de Uzcátegui CE, de Uzcátegui N, Collins ML, Sener EC, Wabbels B, Hellebrand H, Meitinger T, de Berardinis T, Magli A, Schiavi C, Pastore-Trossello M, Koc F, Wong AM, Levin AV, Geraghty MT, Descartes M, Flaherty M, Jamieson RV, Møller HU, Meuthen I, Callen DF, Kerwin J, Lindsay S, Meindl A, Gupta ML, Pellman D, Engle EC. Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance. Cell 2010; 140:74-87. PubMed
  • Rhodes J, Amsterdam A, Sanda T, Moreau LA, McKenna K, Heinrichs S, Ganem NJ, Ho KW, Neuberg DS, Johnston A, Ahn Y, Kutok JL, Hromas R, Wray J, Lee C, Murphy C, Radtke I, Downing JR, Fleming MD, MacConaill LE, Amatruda JF, Gutierrez A, Galinsky I, Stone RM, Ross EA, Pellman DS, Kanki JP, Look AT. Emi1 maintains genomic integrity during zebrafish embryogenesis and cooperates with p53 in tumor suppression. Mol Cell Biol 2009; 29:5911-22. PubMed
  • Yoshida S, Bartolini S, Pellman D. Mechanisms for concentrating Rho1 during cytokinesis. Genes Dev 2009; 23:810-23. PubMed
  • Chandhok NS, Pellman D. A little CIN may cost a lot: revisiting aneuploidy and cancer. Curr Opin Genet Dev 2009; 19:74-81. PubMed
  • Atkins BD, Yoshida S, Pellman D. Symmetry breaking: scaffold plays matchmaker for polarity signaling proteins. Curr Biol 2008; 18:R1130-2. PubMed
  • Kwon M, Godinho SA, Chandhok NS, Ganem NJ, Azioune A, Thery M, Pellman D. Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes. Genes Dev 2008; 22:2189-203. PubMed
  • Austin KM, Gupta ML, Coats SA, Tulpule A, Mostoslavsky G, Balazs AB, Mulligan RC, Daley G, Pellman D, Shimamura A. Mitotic spindle destabilization and genomic instability in Shwachman-Diamond syndrome. J Clin Invest 2008; 118:1511-8. PubMed
  • Kono K, Nogami S, Abe M, Nishizawa M, Morishita S, Pellman D, Ohya Y. G1/S Cyclin-Dependent Kinase Regulates Small GTPase Rho1p through Phosphorylation of RhoGEF Tus1p in Saccharomyces cerevisiae. Mol Biol Cell 2008; 19:1763-71. PubMed
  • Yoshida S, Pellman D. Plugging the GAP between cell polarity and cell cycle. EMBO Rep 2008; 9:39-41. PubMed
  • Sch. Forkhead transcription factor FoxM1 regulates mitotic entry and prevents spindle defects in cerebellar granule neuron precursors. Mol Cell Biol 2007; 27:8259-70. PubMed
  • Ganem NJ, Pellman D. Limiting the proliferation of polyploid cells. Cell 2007; 131:437-40. PubMed
  • Ceol CJ, Pellman D, Zon LI. APC and colon cancer: two hits for one. Nat Med 2007; 13:1286-7. PubMed
  • Jallepalli PV, Pellman D. Cell biology. Aneuploidy in the balance. Science 2007; 317:904-5. PubMed
  • Buttery SM, Yoshida S, Pellman D. Yeast formins Bni1 and Bnr1 utilize different modes of cortical interaction during the assembly of actin cables. Mol Biol Cell 2007; 18:1826-38. PubMed
  • Ganem NJ, Storchova Z, Pellman D. Tetraploidy, aneuploidy and cancer. Curr Opin Genet Dev 2007; 17:157-62. PubMed
  • Pellman D. Cell biology: aneuploidy and cancer. Nature 2007; 446:38-9. PubMed
  • Storchov. Genome-wide genetic analysis of polyploidy in yeast. Nature 2006; 443:541-7. PubMed
  • Gupta ML, Carvalho P, Roof DM, Pellman D. Plus end-specific depolymerase activity of Kip3, a kinesin-8 protein, explains its role in positioning the yeast mitotic spindle. Nat Cell Biol 2006; 8:913-23. PubMed
  • Yoshida S, Kono K, Lowery DM, Bartolini S, Yaffe MB, Ohya Y, Pellman D. Polo-like kinase Cdc5 controls the local activation of Rho1 to promote cytokinesis. Science 2006; 313:108-11. PubMed
  • Yi C, McCarty JH, Troutman SA, Eckman MS, Bronson RT, Kissil JL. Loss of the putative tumor suppressor band 4.1B/Dal1 gene is dispensable for normal development and does not predispose to cancer. Mol Cell Biol 2005; 25:10052-9. PubMed
  • Fujiwara T, Bandi M, Nitta M, Ivanova EV, Bronson RT, Pellman D. Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells. Nature 2005; 437:1043-7. PubMed
  • Yoshida S, Guillet M, Pellman D. MEN signaling: daughter bound pole must escape her mother to be fully active. Dev Cell 2005; 9:168-70. PubMed
  • Carvalho P, Pellman D. Mitotic spindle: laser microsurgery in yeast cells. Curr Biol 2004; 14:R748-50. PubMed
  • Andalis AA, Storchova Z, Styles C, Galitski T, Pellman D, Fink GR. Defects arising from whole-genome duplications in Saccharomyces cerevisiae. Genetics 2004; 167:1109-21. PubMed
  • Carvalho P, Gupta ML, Hoyt MA, Pellman D. Cell cycle control of kinesin-mediated transport of Bik1 (CLIP-170) regulates microtubule stability and dynein activation. Dev Cell 2004; 6:815-29. PubMed
  • Molk JN, Schuyler SC, Liu JY, Evans JG, Salmon ED, Pellman D, Bloom K. The differential roles of budding yeast Tem1p, Cdc15p, and Bub2p protein dynamics in mitotic exit. Mol Biol Cell 2004; 15:1519-32. PubMed
  • Xu Y, Moseley JB, Sagot I, Poy F, Pellman D, Goode BL, Eck MJ. Crystal structures of a Formin Homology-2 domain reveal a tethered dimer architecture. Cell 2004; 116:711-23. PubMed
  • Moseley JB, Sagot I, Manning AL, Xu Y, Eck MJ, Pellman D, Goode BL. A conserved mechanism for Bni1- and mDia1-induced actin assembly and dual regulation of Bni1 by Bud6 and profilin. Mol Biol Cell 2003; 15:896-907. PubMed
  • Storchova Z, Pellman D. From polyploidy to aneuploidy, genome instability and cancer. Nat Rev Mol Cell Biol 2004; 5:45-54. PubMed
  • Carvalho P, Tirnauer JS, Pellman D. Surfing on microtubule ends. Trends Cell Biol 2003; 13:229-37. PubMed
  • Chestukhin A, Pfeffer C, Milligan S, DeCaprio JA, Pellman D. Processing, localization, and requirement of human separase for normal anaphase progression. Proc Natl Acad Sci U S A 2003; 100:4574-9. PubMed
  • Sheeman B, Carvalho P, Sagot I, Geiser J, Kho D, Hoyt MA, Pellman D. Determinants of S. cerevisiae dynein localization and activation: implications for the mechanism of spindle positioning. Curr Biol 2003; 13:364-72. PubMed
  • Schuyler SC, Liu JY, Pellman D. The molecular function of Ase1p: evidence for a MAP-dependent midzone-specific spindle matrix. Microtubule-associated proteins. J Cell Biol 2003; 160:517-28. PubMed
  • Leader B, Lim H, Carabatsos MJ, Harrington A, Ecsedy J, Pellman D, Maas R, Leder P. Formin-2, polyploidy, hypofertility and positioning of the meiotic spindle in mouse oocytes. Nat Cell Biol 2002; 4:921-8. PubMed
  • Sagot I, Rodal AA, Moseley J, Goode BL, Pellman D. An actin nucleation mechanism mediated by Bni1 and profilin. Nat Cell Biol 2002; 4:626-31. PubMed
  • Schuyler SC, Pellman D. Analysis of the size and shape of protein complexes from yeast. Methods Enzymol 2002; 351:150-68. PubMed
  • Sagot I, Klee SK, Pellman D. Yeast formins regulate cell polarity by controlling the assembly of actin cables. Nat Cell Biol 2001; 4:42-50. PubMed
  • Lin H, de Carvalho P, Kho D, Tai CY, Pierre P, Fink GR, Pellman D. Polyploids require Bik1 for kinetochore-microtubule attachment. J Cell Biol 2002; 155:1173-84. PubMed
  • Yarm F, Sagot I, Pellman D. The social life of actin and microtubules: interaction versus cooperation. Curr Opin Microbiol 2001; 4:696-702. PubMed
  • Lechler T, Jonsdottir GA, Klee SK, Pellman D, Li R. A two-tiered mechanism by which Cdc42 controls the localization and activation of an Arp2/3-activating motor complex in yeast. J Cell Biol 2001; 155:261-70. PubMed
  • Pellman D, Christman MF. Separase anxiety: dissolving the sister bond and more. Nat Cell Biol 2001; 3:E207-9. PubMed
  • Huang JN, Park I, Ellingson E, Littlepage LE, Pellman D. Activity of the APC(Cdh1) form of the anaphase-promoting complex persists until S phase and prevents the premature expression of Cdc20p. J Cell Biol 2001; 154:85-94. PubMed
  • Schuyler SC, Pellman D. Microtubule "plus-end-tracking proteins": The end is just the beginning. Cell 2001; 105:421-4. PubMed
  • J. Rvb1p and Rvb2p are essential components of a chromatin remodeling complex that regulates transcription of over 5% of yeast genes. J Biol Chem 2001; 276:16279-88. PubMed
  • Pellman D. Cancer. A CINtillating new job for the APC tumor suppressor. Science 2001; 291:2555-6. PubMed
  • Schuyler SC, Pellman D. Search, capture and signal: games microtubules and centrosomes play. J Cell Sci 2001; 114:247-55. PubMed
  • Lee L, Tirnauer JS, Li J, Schuyler SC, Liu JY, Pellman D. Positioning of the mitotic spindle by a cortical-microtubule capture mechanism. Science 2000; 287:2260-2. PubMed
  • Kwon M, Godinho SA, Chandhok NS, Ganem NJ, Azioune A, Thery M, Pellman D. Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes. Genes Dev 2008.
  • Tirnauer JS, O'Toole E, Berrueta L, Bierer BE, Pellman D. Yeast Bim1p promotes the G1-specific dynamics of microtubules. J Cell Biol 1999; 145:993-1007. PubMed
  • Berrueta L, Tirnauer JS, Schuyler SC, Pellman D, Bierer BE. The APC-associated protein EB1 associates with components of the dynactin complex and cytoplasmic dynein intermediate chain. Curr Biol 1999; 9:425-8. PubMed
  • Lee L, Klee SK, Evangelista M, Boone C, Pellman D. Control of mitotic spindle position by the Saccharomyces cerevisiae formin Bni1p. J Cell Biol 1999; 144:947-61. PubMed
  • Berrueta L, Kraeft SK, Tirnauer JS, Schuyler SC, Chen LB, Hill DE, Pellman D, Bierer BE. The adenomatous polyposis coli-binding protein EB1 is associated with cytoplasmic and spindle microtubules. Proc Natl Acad Sci U S A 1998; 95:10596-601. PubMed
  • D'Andrea A, Pellman D. Deubiquitinating enzymes: a new class of biological regulators. Crit Rev Biochem Mol Biol 1998; 33:337-52. PubMed
  • DeZwaan TM, Ellingson E, Pellman D, Roof DM. Kinesin-related KIP3 of Saccharomyces cerevisiae is required for a distinct step in nuclear migration. J Cell Biol 1997; 138:1023-40. PubMed
  • Juang YL, Huang J, Peters JM, McLaughlin ME, Tai CY, Pellman D. APC-mediated proteolysis of Ase1 and the morphogenesis of the mitotic spindle. Science 1997; 275:1311-4. PubMed
  • Pellman D, Bagget M, Tu YH, Fink GR, Tu H. Two microtubule-associated proteins required for anaphase spindle movement in Saccharomyces cerevisiae. J Cell Biol 1995; 130:1373-85. PubMed
  • Loeb JD, Schlenstedt G, Pellman D, Kornitzer D, Silver PA, Fink GR. The yeast nuclear import receptor is required for mitosis. Proc Natl Acad Sci U S A 1995; 92:7647-51. PubMed
  • Pellman D, McLaughlin ME, Fink GR. TATA-dependent and TATA-independent transcription at the HIS4 gene of yeast. Nature 1990; 348:82-5. PubMed
  • Stoeckle MY, Sugano S, Hampe A, Vashistha A, Pellman D, Hanafusa H. 78-kilodalton glucose-regulated protein is induced in Rous sarcoma virus-transformed cells independently of glucose deprivation. Mol Cell Biol 1988; 8:2675-80. PubMed
  • Pellman D, Garber EA, Cross FR, Hanafusa H. An N-terminal peptide from p60src can direct myristylation and plasma membrane localization when fused to heterologous proteins. Nature 1985; 314:374-7. PubMed
  • Pellman D, Garber EA, Cross FR, Hanafusa H. Fine structural mapping of a critical NH2-terminal region of p60src. Proc Natl Acad Sci U S A 1985; 82:1623-7. PubMed
  • Cross FR, Garber EA, Pellman D, Hanafusa H. A short sequence in the p60src N terminus is required for p60src myristylation and membrane association and for cell transformation. Mol Cell Biol 1984; 4:1834-42. PubMed
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