Timothy J. Mitchison, PhD

Harvard Medical School

Harvard Medical School
Phone: (617) 432-3805
Fax: (617) 432-3702


timothy_mitchison@hms.harvard.edu

Timothy J. Mitchison, PhD

Harvard Medical School

EDUCATIONAL TITLES

  • Hasib Sabbagh Professor of Systems Biology, Systems Biology, Harvard Medical School
  • Deputy Chairman, Systems Biology, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Publications

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  • Özlü N, Qureshi MH, Toyoda Y, Renard BY, Mollaoglu G, Özkan NE, Bulbul S, Poser I, Timm W, Hyman AA, Mitchison TJ, Steen JA. Quantitative comparison of a human cancer cell surface proteome between interphase and mitosis. EMBO J 2015; 34:251-65. PubMed
  • Coughlin M, Groen AC, Mitchison TJ. Electron microscopy of microtubule cytoskeleton assembly in vitro. Methods Mol Biol 2013; 1117:259-71. PubMed
  • Groen AC, Ngyuen PA, Field CM, Ishihara K, Mitchison TJ. Glycogen-supplemented mitotic cytosol for analyzing Xenopus egg microtubule organization. Methods Enzymol 2014; 540:417-33. PubMed
  • Wang Y, Lee YM, Baitsch L, Huang A, Xiang Y, Tong H, Lako A, Von T, Choi C, Lim E, Min J, Li L, Stegmeier F, Schlegel R, Eck MJ, Gray NS, Mitchison TJ, Zhao JJ. MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells. Elife 2014. PubMed
  • Field CM, Nguyen PA, Ishihara K, Groen AC, Mitchison TJ. Xenopus egg cytoplasm with intact actin. Methods Enzymol 2014; 540:399-415. PubMed
  • Prentice-Mott HV, Chang CH, Mahadevan L, Mitchison TJ, Irimia D, Shah JV. Biased migration of confined neutrophil-like cells in asymmetric hydraulic environments. Proc Natl Acad Sci U S A 2013; 110:21006-11. PubMed
  • Tang Y, Xie T, Florian S, Moerke N, Shamu C, Benes C, Mitchison TJ. Differential determinants of cancer cell insensitivity to antimitotic drugs discriminated by a one-step cell imaging assay. J Biomol Screen 2013; 18:1062-71. PubMed
  • Zidovska A, Weitz DA, Mitchison TJ. Micron-scale coherence in interphase chromatin dynamics. Proc Natl Acad Sci U S A 2013; 110:15555-60. PubMed
  • Thurber GM, Yang KS, Reiner T, Kohler RH, Sorger P, Mitchison T, Weissleder R. Single-cell and subcellular pharmacokinetic imaging allows insight into drug action in vivo. Nat Commun 2013; 4:1504. PubMed
  • Barkauskaite E, Brassington A, Tan ES, Warwicker J, Dunstan MS, Banos B, Lafite P, Ahel M, Mitchison TJ, Ahel I, Leys D. Visualization of poly(ADP-ribose) bound to PARG reveals inherent balance between exo- and endo-glycohydrolase activities. Nat Commun 2013; 4:2164. PubMed
  • Tan ES, Krukenberg KA, Mitchison TJ. Large-scale preparation and characterization of poly(ADP-ribose) and defined length polymers. Anal Biochem 2012; 428:126-36. PubMed
  • Zhang X, Wang W, Bedigian AV, Coughlin ML, Mitchison TJ, Eggert US. Dopamine receptor D3 regulates endocytic sorting by a Prazosin-sensitive interaction with the coatomer COPI. Proc Natl Acad Sci U S A 2012; 109:12485-90. PubMed
  • Dumont S, Salmon ED, Mitchison TJ. Deformations within moving kinetochores reveal different sites of active and passive force generation. Science 2012; 337:355-8. PubMed
  • Hu CK, Ozlü N, Coughlin M, Steen JJ, Mitchison TJ. Plk1 negatively regulates PRC1 to prevent premature midzone formation before cytokinesis. Mol Biol Cell 2012; 23:2702-11. PubMed
  • Kim S, Peshkin L, Mitchison TJ. Vascular disrupting agent drug classes differ in effects on the cytoskeleton. PLoS ONE 2012; 7:e40177. PubMed
  • Wühr M, Tan ES, Parker SK, Detrich HW, Mitchison TJ. A model for cleavage plane determination in early amphibian and fish embryos. Curr Biol 2010; 20:2040-5. PubMed
  • Mitchison TJ. Remaining mysteries of the cytoplasm. Mol Biol Cell 2010; 21:3811-2. PubMed
  • Kueh HY, Brieher WM, Mitchison TJ. Quantitative analysis of actin turnover in Listeria comet tails: evidence for catastrophic filament turnover. Biophys J 2010; 99:2153-62. PubMed
  • Huang HC, Shi J, Orth JD, Mitchison TJ. Cell death when the SAC is out of commission. Cell Cycle 2010. PubMed
  • Martin DS, Fathi R, Mitchison TJ, Gelles J. FRET measurements of kinesin neck orientation reveal a structural basis for processivity and asymmetry. Proc Natl Acad Sci U S A 2010; 107:5453-8. PubMed
  • Gatlin JC, Matov A, Danuser G, Mitchison TJ, Salmon ED. Directly probing the mechanical properties of the spindle and its matrix. J Cell Biol 2010; 188:481-9. PubMed
  • Ozlü N, Monigatti F, Renard BY, Field CM, Steen H, Mitchison TJ, Steen JJ. Binding partner switching on microtubules and aurora-B in the mitosis to cytokinesis transition. Mol Cell Proteomics 2010; 9:336-50. PubMed
  • Huang HC, Mitchison TJ, Shi J. Stochastic competition between mechanistically independent slippage and death pathways determines cell fate during mitotic arrest. PLoS ONE 2011; 5:e15724. PubMed
  • Chang P, Coughlin M, Mitchison TJ. Interaction between Poly(ADP-ribose) and NuMA contributes to mitotic spindle pole assembly. Mol Biol Cell 2009; 20:4575-85. PubMed
  • Huang HC, Shi J, Orth JD, Mitchison TJ. Evidence that mitotic exit is a better cancer therapeutic target than spindle assembly. Cancer Cell 2009; 16:347-58. PubMed
  • Charras GT, Mitchison TJ, Mahadevan L. Animal cell hydraulics. J Cell Sci 2009; 122:3233-41. PubMed
  • Dumont S, Mitchison TJ. Force and length in the mitotic spindle. Curr Biol 2009; 19:R749-61. PubMed
  • Kueh HY, Mitchison TJ. Structural plasticity in actin and tubulin polymer dynamics. Science 2009; 325:960-3. PubMed
  • Maresca TJ, Groen AC, Gatlin JC, Ohi R, Mitchison TJ, Salmon ED. Spindle assembly in the absence of a RanGTP gradient requires localized CPC activity. Curr Biol 2009; 19:1210-5. PubMed
  • Dumont S, Mitchison TJ. Compression regulates mitotic spindle length by a mechanochemical switch at the poles. Curr Biol 2009; 19:1086-95. PubMed
  • Feng Y, Mitchison TJ, Bender A, Young DW, Tallarico JA. Multi-parameter phenotypic profiling: using cellular effects to characterize small-molecule compounds. Nat Rev Drug Discov 2009; 8:567-78. PubMed
  • Niethammer P, Grabher C, Look AT, Mitchison TJ. A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish. Nature 2009; 459:996-9. PubMed
  • Needleman DJ, Xu Y, Mitchison TJ. Pin-hole array correlation imaging: highly parallel fluorescence correlation spectroscopy. Biophys J 2009; 96:5050-9. PubMed
  • Groen AC,Maresca TJ,Gatlin JC,Salmon ED,Mitchison TJ. Functional overlap of microtubule assembly factors in chromatin-promoted spindle assembly. Mol Biol Cell 2009; 20:2766-73. PubMed
  • Gatlin JC,Matov A,Groen AC,Needleman DJ,Maresca TJ,Danuser G,Mitchison TJ,Salmon ED. Spindle fusion requires dynein-mediated sliding of oppositely oriented microtubules. Curr Biol 2009; 19:287-96. PubMed
  • Tsui M, Xie T, Orth JD, Carpenter AE, Rudnicki S, Kim S, Shamu CE, Mitchison TJ. An intermittent live cell imaging screen for siRNA enhancers and suppressors of a kinesin-5 inhibitor. PLoS ONE 2009; 4:e7339. PubMed
  • Orth JD,Tang Y,Shi J,Loy CT,Amendt C,Wilm C,Zenke FT,Mitchison TJ. Quantitative live imaging of cancer and normal cells treated with Kinesin-5 inhibitors indicates significant differences in phenotypic responses and cell fate. Mol Cancer Ther 2008; 7:3480-9. PubMed
  • Maloney KN,Fujita M,Eggert US,Schroeder FC,Field CM,Mitchison TJ,Clardy J. Actin-Aggregating Cucurbitacins from Physocarpus capitatus. J Nat Prod 2008. PubMed
  • Kueh HY,Brieher WM,Mitchison TJ. Dynamic stabilization of actin filaments. Proc Natl Acad Sci U S A 2008; 105:16531-6. PubMed
  • Wuhr M,Mitchison TJ,Field CM. Mitosis: new roles for myosin-X and actin at the spindle. Curr Biol 2008; 18:R912-4. PubMed
  • Wuhr M,Chen Y,Dumont S,Groen AC,Needleman DJ,Salic A,Mitchison TJ. Evidence for an upper limit to mitotic spindle length. Curr Biol 2008; 18:1256-61. PubMed
  • Kueh HY,Charras GT,Mitchison TJ,Brieher WM. Actin disassembly by cofilin, coronin, and Aip1 occurs in bursts and is inhibited by barbed-end cappers. J Cell Biol 2008; 182:341-53. PubMed
  • Groen AC,Needleman D,Brangwynne C,Gradinaru C,Fowler B,Mazitschek R,Mitchison TJ. A novel small-molecule inhibitor reveals a possible role of kinesin-5 in anastral spindle-pole assembly. J Cell Sci 2008; 121:2293-300. PubMed
  • Mitchison TJ, Charras GT, Mahadevan L. Implications of a poroelastic cytoplasm for the dynamics of animal cell shape. Semin Cell Dev Biol 2008; 19:215-23. PubMed
  • Niethammer P, Kueh HY, Mitchison TJ. Spatial patterning of metabolism by mitochondria, oxygen, and energy sinks in a model cytoplasm. Curr Biol 2008; 18:586-91. PubMed
  • Hu CK, Coughlin M, Field CM, Mitchison TJ. Cell polarization during monopolar cytokinesis. J Cell Biol 2008; 181:195-202. PubMed
  • Charras GT, Coughlin M, Mitchison TJ, Mahadevan L. Life and times of a cellular bleb. Biophys J 2007; 94:1836-53. PubMed
  • Galkin VE, Orlova A, Brieher W, Kueh HY, Mitchison TJ, Egelman EH. Coronin-1A stabilizes F-actin by bridging adjacent actin protomers and stapling opposite strands of the actin filament. J Mol Biol 2008; 376:607-13. PubMed
  • Salic A, Mitchison TJ. A chemical method for fast and sensitive detection of DNA synthesis in vivo. Proc Natl Acad Sci U S A 2008; 105:2415-20. PubMed
  • Young DW, Bender A, Hoyt J, McWhinnie E, Chirn GW, Tao CY, Tallarico JA, Labow M, Jenkins JL, Mitchison TJ, Feng Y. Integrating high-content screening and ligand-target prediction to identify mechanism of action. Nat Chem Biol 2007; 4:59-68. PubMed
  • Irimia D, Charras G, Agrawal N, Mitchison T, Toner M. Polar stimulation and constrained cell migration in microfluidic channels. Lab Chip 2007; 7:1783-90. PubMed
  • Vrabioiu AM, Mitchison TJ. Symmetry of septin hourglass and ring structures. J Mol Biol 2007; 372:37-49. PubMed
  • Burbank KS, Mitchison TJ, Fisher DS. Slide-and-cluster models for spindle assembly. Curr Biol 2007; 17:1373-83. PubMed
  • Ohi R, Burbank K, Liu Q, Mitchison TJ. Nonredundant functions of Kinesin-13s during meiotic spindle assembly. Curr Biol 2007; 17:953-9. PubMed
  • Eggert US, Kiger AA, Richter C, Perlman ZE, Perrimon N, Mitchison TJ, Field CM. Parallel Chemical Genetic and Genome-Wide RNAi Screens Identify Cytokinesis Inhibitors and Targets. PLoS Biol 2004; 2:e379. PubMed
  • Venkatesh N, Feng Y, DeDecker B, Yacono P, Golan D, Mitchison T, McKeon F. Chemical genetics to identify NFAT inhibitors: potential of targeting calcium mobilization in immunosuppression. Proc Natl Acad Sci U S A 2004; 101:8969-74. PubMed
  • Peterson JR, Lokey RS, Mitchison TJ, Kirschner MW. A chemical inhibitor of N-WASP reveals a new mechanism for targeting protein interactions. Proc Natl Acad Sci U S A 2001; 98:10624-9. PubMed
  • Degterev A, Lugovskoy A, Cardone M, Mulley B, Wagner G, Mitchison T, Yuan J. Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL. Nat Cell Biol 2001; 3:173-82. PubMed
  • Kapoor TM, Mitchison TJ. Allele-specific activators and inhibitors for kinesin. Proc Natl Acad Sci U S A 1999; 96:9106-11. PubMed
  • Desai A, Verma S, Mitchison TJ, Walczak CE. Kin I kinesins are microtubule-destabilizing enzymes. Cell 1999; 96:69-78. PubMed
  • Frazier JA, Wong ML, Longtine MS, Pringle JR, Mann M, Mitchison TJ, Field C. Polymerization of purified yeast septins: evidence that organized filament arrays may not be required for septin function. J Cell Biol 1998; 143:737-49. PubMed
  • Welch MD, Rosenblatt J, Skoble J, Portnoy DA, Mitchison TJ. Interaction of human Arp2/3 complex and the Listeria monocytogenes ActA protein in actin filament nucleation. Science 1998; 281:105-8. PubMed
  • Desai A, Mitchison TJ. Tubulin and FtsZ structures: functional and therapeutic implications. Bioessays 1998; 20:523-7. PubMed
  • Walczak CE, Vernos I, Mitchison TJ, Karsenti E, Heald R. A model for the proposed roles of different microtubule-based motor proteins in establishing spindle bipolarity. Curr Biol 1998; 8:903-13. PubMed
  • Desai A, Maddox PS, Mitchison TJ, Salmon ED. Anaphase A chromosome movement and poleward spindle microtubule flux occur At similar rates in Xenopus extract spindles. J Cell Biol 1998; 141:703-13. PubMed
  • Mitchison TJ, Sawin KE, Theriot JA, Gee K, Mallavarapu A. Caged fluorescent probes. Methods Enzymol 1998; 291:63-78. PubMed
  • Welch MD, DePace AH, Verma S, Iwamatsu A, Mitchison TJ. The human Arp2/3 complex is composed of evolutionarily conserved subunits and is localized to cellular regions of dynamic actin filament assembly. J Cell Biol 1997; 138:375-84. PubMed
  • Rosenblatt J, Agnew BJ, Abe H, Bamburg JR, Mitchison TJ. Xenopus actin depolymerizing factor/cofilin (XAC) is responsible for the turnover of actin filaments in Listeria monocytogenes tails. J Cell Biol 1997; 136:1323-32. PubMed
  • Cramer LP, Siebert M, Mitchison TJ. Identification of novel graded polarity actin filament bundles in locomoting heart fibroblasts: implications for the generation of motile force. J Cell Biol 1997; 136:1287-305. PubMed
  • Walczak CE, Verma S, Mitchison TJ. XCTK2: a kinesin-related protein that promotes mitotic spindle assembly in Xenopus laevis egg extracts. J Cell Biol 1997; 136:859-70. PubMed
  • Welch MD, Mallavarapu A, Rosenblatt J, Mitchison TJ. Actin dynamics in vivo. Curr Opin Cell Biol 1997; 9:54-61. PubMed
  • Welch MD, Iwamatsu A, Mitchison TJ. Actin polymerization is induced by Arp2/3 protein complex at the surface of Listeria monocytogenes. Nature 1997; 385:265-9. PubMed
  • Cramer LP, Mitchison TJ. Investigation of the mechanism of retraction of the cell margin and rearward flow of nodules during mitotic cell rounding. Mol Biol Cell 1997; 8:109-19. PubMed
  • Desai A, Mitchison TJ. Microtubule polymerization dynamics. Annu Rev Cell Dev Biol 1998; 13:83-117. PubMed
  • Field CM, al-Awar O, Rosenblatt J, Wong ML, Alberts B, Mitchison TJ. A purified Drosophila septin complex forms filaments and exhibits GTPase activity. J Cell Biol 1996; 133:605-16. PubMed
  • Belmont LD, Mitchison TJ. Identification of a protein that interacts with tubulin dimers and increases the catastrophe rate of microtubules. Cell 1996; 84:623-31. PubMed
  • Mitchison TJ, Cramer LP. Actin-based cell motility and cell locomotion. Cell 1996; 84:371-9. PubMed
  • Walczak CE, Mitchison TJ, Desai A. XKCM1: a Xenopus kinesin-related protein that regulates microtubule dynamics during mitotic spindle assembly. Cell 1996; 84:37-47. PubMed
  • Cramer LP, Mitchison TJ. Myosin is involved in postmitotic cell spreading. J Cell Biol 1995; 131:179-89. PubMed
  • Mitchison TJ. Evolution of a dynamic cytoskeleton. Philos Trans R Soc Lond B Biol Sci 1995; 349:299-304. PubMed
  • Wordeman L, Mitchison TJ. Identification and partial characterization of mitotic centromere-associated kinesin, a kinesin-related protein that associates with centromeres during mitosis. J Cell Biol 1995; 128:95-104. PubMed
  • Hirano T, Mitchison TJ. A heterodimeric coiled-coil protein required for mitotic chromosome condensation in vitro. Cell 1994; 79:449-58. PubMed
  • Mitchison TJ. Towards a pharmacological genetics. Chem Biol 1998; 1:3-6. PubMed
  • Theriot JA, Rosenblatt J, Portnoy DA, Goldschmidt-Clermont PJ, Mitchison TJ. Involvement of profilin in the actin-based motility of L. monocytogenes in cells and in cell-free extracts. Cell 1994; 76:505-17. PubMed
  • Sawin KE, Mitchison TJ. Microtubule flux in mitosis is independent of chromosomes, centrosomes, and antiparallel microtubules. Mol Biol Cell 1994; 5:217-26. PubMed
  • Mitchison TJ. Localization of an exchangeable GTP binding site at the plus end of microtubules. Science 1993; 261:1044-7. PubMed
  • Cramer L, Mitchison TJ. Moving and stationary actin filaments are involved in spreading of postmitotic PtK2 cells. J Cell Biol 1993; 122:833-43. PubMed
  • Mitchison TJ, Salmon ED. Poleward kinetochore fiber movement occurs during both metaphase and anaphase-A in newt lung cell mitosis. J Cell Biol 1992; 119:569-82. PubMed
  • Hyman AA, Middleton K, Centola M, Mitchison TJ, Carbon J. Microtubule-motor activity of a yeast centromere-binding protein complex. Nature 1992; 359:533-6. PubMed
  • Sawin KE, LeGuellec K, Philippe M, Mitchison TJ. Mitotic spindle organization by a plus-end-directed microtubule motor. Nature 1992; 359:540-3. PubMed
  • Theriot JA, Mitchison TJ, Tilney LG, Portnoy DA. The rate of actin-based motility of intracellular Listeria monocytogenes equals the rate of actin polymerization. Nature 1992; 357:257-60. PubMed
  • Mitchison TJ. Self-organization of polymer-motor systems in the cytoskeleton. Philos Trans R Soc Lond B Biol Sci 1992; 336:99-106. PubMed
  • Sawin KE, Mitchison TJ, Wordeman LG. Evidence for kinesin-related proteins in the mitotic apparatus using peptide antibodies. J Cell Sci 1992; 101 ( Pt 2):303-13. PubMed
  • Hirano T, Mitchison TJ. Cell cycle control of higher-order chromatin assembly around naked DNA in vitro. J Cell Biol 1991; 115:1479-89. PubMed
  • Symons MH, Mitchison TJ. Control of actin polymerization in live and permeabilized fibroblasts. J Cell Biol 1991; 114:503-13. PubMed
  • Theriot JA, Mitchison TJ. Actin microfilament dynamics in locomoting cells. Nature 1991; 352:126-31. PubMed
  • Hyman AA, Mitchison TJ. Two different microtubule-based motor activities with opposite polarities in kinetochores. Nature 1991; 351:206-11. PubMed
  • Sawin KE, Mitchison TJ. Poleward microtubule flux mitotic spindles assembled in vitro. J Cell Biol 1991; 112:941-54. PubMed
  • Mitchison TJ. Polewards microtubule flux in the mitotic spindle: evidence from photoactivation of fluorescence. J Cell Biol 1989; 109:637-52. PubMed
  • Mitchison TJ. Mitosis: basic concepts. Curr Opin Cell Biol 1989; 1:67-74. PubMed
  • Kirschner MW, Mitchison T. Microtubule dynamics. Nature 1986; 324:621. PubMed
  • Mitchison TJ, Kirschner MW. Properties of the kinetochore in vitro. II. Microtubule capture and ATP-dependent translocation. J Cell Biol 1985; 101:766-77. PubMed
  • Mitchison TJ, Kirschner MW. Properties of the kinetochore in vitro. I. Microtubule nucleation and tubulin binding. J Cell Biol 1985; 101:755-65. PubMed
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