Photo of Marc W. Kirschner,  PhD

Marc W. Kirschner, PhD

Harvard Medical School

Harvard Medical School
Phone: (617) 432-2250


marc@hms.harvard.edu

Marc W. Kirschner, PhD

Harvard Medical School

EDUCATIONAL TITLES

  • John Franklin Enders University Professor of Systems Biology, Systems Biology, Harvard Medical School
  • Chair, Systems Biology, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

My research concerns the regulation of the cell cycle, the nature of hte cytoskeleton, and mechanisms of early vertebrate development. In particular we are concerned with the role of proteolysis in the exit from mitosis and the checkpoint mechanisms at work there. We are also concerned with the role of proteolysis during the G1 period. We have used Xenopus eggs and extracts to dissect these mechanisms biochemically. In addition we have been interested in understanding how actin assembly is regulated by signal transduction mechanisms. Finally, we are trying to understand the early signaling and patterning events of the frog embryo and how these events lead to the establishment of the vertebrate body plan.

Publications

Powered by Harvard Catalyst
  • Klein AM, Mazutis L, Akartuna I, Tallapragada N, Veres A, Li V, Peshkin L, Weitz DA, Kirschner MW. Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell 2015; 161:1187-201. PubMed
  • Lu Y, Lee BH, King RW, Finley D, Kirschner MW. Substrate degradation by the proteasome: a single-molecule kinetic analysis. Science 2015; 348:1250834. PubMed
  • Lu Y, Wang W, Kirschner MW. Specificity of the anaphase-promoting complex: a single-molecule study. Science 2015; 348:1248737. PubMed
  • Gujral TS, Chan M, Peshkin L, Sorger PK, Kirschner MW, MacBeath G. A noncanonical Frizzled2 pathway regulates epithelial-mesenchymal transition and metastasis. Cell 2014; 159:844-56. PubMed
  • Thompson JW, Nagel J, Hoving S, Gerrits B, Bauer A, Thomas JR, Kirschner MW, Schirle M, Luchansky SJ. Quantitative Lys-狼-Gly-Gly (diGly) Proteomics Coupled with Inducible RNAi Reveals Ubiquitin-mediated Proteolysis of DNA Damage-inducible Transcript 4 (DDIT4) by the E3 Ligase HUWE1. J Biol Chem 2014; 289:28942-55. PubMed
  • Zhao R, Deibler RW, Lerou PH, Ballabeni A, Heffner GC, Cahan P, Unternaehrer JJ, Kirschner MW, Daley GQ. A nontranscriptional role for Oct4 in the regulation of mitotic entry. Proc Natl Acad Sci U S A 2014. PubMed
  • Wühr M, Freeman RM, Presler M, Horb ME, Peshkin L, Gygi SP, Kirschner MW. Deep proteomics of the Xenopus laevis egg using an mRNA-derived reference database. Curr Biol 2014; 24:1467-75. PubMed
  • Li VC, Kirschner MW. Molecular ties between the cell cycle and differentiation in embryonic stem cells. Proc Natl Acad Sci U S A 2014; 111:9503-8. PubMed
  • Wan L, Tan M, Yang J, Inuzuka H, Dai X, Wu T, Liu J, Shaik S, Chen G, Deng J, Malumbres M, Letai A, Kirschner MW, Sun Y, Wei W. APC(Cdc20) Suppresses Apoptosis through Targeting Bim for Ubiquitination and Destruction. Dev Cell 2014; 29:377-91. PubMed
  • Liu P, Begley M, Michowski W, Inuzuka H, Ginzberg M, Gao D, Tsou P, Gan W, Papa A, Kim BM, Wan L, Singh A, Zhai B, Yuan M, Wang Z, Gygi SP, Lee TH, Lu KP, Toker A, Pandolfi PP, Asara JM, Kirschner MW, Sicinski P, Cantley L, Wei W. Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus. Nature 2014; 508:541-5. PubMed
  • Ortiz-Meoz RF, Merbl Y, Kirschner MW, Walker S. Microarray Discovery of New OGT Substrates: The Medulloblastoma Oncogene OTX2 Is O-GlcNAcylated. J Am Chem Soc 2014; 136:4845-8. PubMed
  • Gujral TS, Peshkin L, Kirschner MW. Exploiting polypharmacology for drug target deconvolution. Proc Natl Acad Sci U S A 2014; 111:5048-53. PubMed
  • Merbl Y, Kirschner MW. Post-Translational Modification Profiling-a High-Content Assay for Identifying Protein Modifications in Mammalian Cellular Systems. Curr Protoc Protein Sci 2014; 77:27.8.1-27.8.13. PubMed
  • Wang W, Wu T, Kirschner MW. The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium. Elife 2014; 3:e03083. PubMed
  • Sung Y, Tzur A, Oh S, Choi W, Li V, Dasari RR, Yaqoob Z, Kirschner MW. Size homeostasis in adherent cells studied by synthetic phase microscopy. Proc Natl Acad Sci U S A 2013; 110:16687-92. PubMed
  • Fukushima H, Ogura K, Wan L, Lu Y, Li V, Gao D, Liu P, Lau AW, Wu T, Kirschner MW, Inuzuka H, Wei W. SCF-mediated Cdh1 degradation defines a negative feedback system that coordinates cell-cycle progression. Cell Rep 2013; 4:803-16. PubMed
  • Ballabeni A, Zamponi R, Moore JK, Helin K, Kirschner MW. Geminin deploys multiple mechanisms to regulate Cdt1 before cell division thus ensuring the proper execution of DNA replication. Proc Natl Acad Sci U S A 2013; 110:E2848-53. PubMed
  • Wang W, Kirschner MW. Emi1 preferentially inhibits ubiquitin chain elongation by the anaphase-promoting complex. Nat Cell Biol 2013; 15:797-806. PubMed
  • Gallop JL, Walrant A, Cantley LC, Kirschner MW. Phosphoinositides and membrane curvature switch the mode of actin polymerization via selective recruitment of toca-1 and Snx9. Proc Natl Acad Sci U S A 2013. PubMed
  • Kafri R, Levy J, Ginzberg MB, Oh S, Lahav G, Kirschner MW. Dynamics extracted from fixed cells reveal feedback linking cell growth to cell cycle. Nature 2013; 494:480-3. PubMed
  • Hernández AR, Klein AM, Kirschner MW. Kinetic responses of 硫-catenin specify the sites of Wnt control. Science 2012; 338:1337-40. PubMed
  • Wühr M, Haas W, McAlister GC, Peshkin L, Rad R, Kirschner MW, Gygi SP. Accurate Multiplexed Proteomics at the MS2 Level Using the Complement Reporter Ion Cluster. Anal Chem 2012; 84:9214-21. PubMed
  • Son S, Tzur A, Weng Y, Jorgensen P, Kim J, Kirschner MW, Manalis SR. Direct observation of mammalian cell growth and size regulation. Nat Methods 2012; 9:910-2. PubMed
  • Li VC, Ballabeni A, Kirschner MW. Gap 1 phase length and mouse embryonic stem cell self-renewal. Proc Natl Acad Sci U S A 2012; 109:12550-5. PubMed
  • Vastag L, Jorgensen P, Peshkin L, Wei R, Rabinowitz JD, Kirschner MW. Remodeling of the metabolome during early frog development. PLoS ONE 2011; 6:e16881. PubMed
  • Wu S, Wang W, Kong X, Congdon LM, Yokomori K, Kirschner MW, Rice JC. Dynamic regulation of the PR-Set7 histone methyltransferase is required for normal cell cycle progression. Genes Dev 2010; 24:2531-42. PubMed
  • Merbl Y, Kirschner MW. Protein microarrays for genome-wide posttranslational modification analysis. 2010. PubMed
  • Lee K, Gallop JL, Rambani K, Kirschner MW. Self-assembly of filopodia-like structures on supported lipid bilayers. Science 2010; 329:1341-5. PubMed
  • Song EJ, Werner SL, Neubauer J, Stegmeier F, Aspden J, Rio D, Harper JW, Elledge SJ, Kirschner MW, Rape M. The Prp19 complex and the Usp4Sart3 deubiquitinating enzyme control reversible ubiquitination at the spliceosome. Genes Dev 2010; 24:1434-47. PubMed
  • Springer M, Weissman JS, Kirschner MW. A general lack of compensation for gene dosage in yeast. Mol Syst Biol 2010; 6:368. PubMed
  • Godin M, Delgado FF, Son S, Grover WH, Bryan AK, Tzur A, Jorgensen P, Payer K, Grossman AD, Kirschner MW, Manalis SR. Using buoyant mass to measure the growth of single cells. Nat Methods 2010; 7:387-90. PubMed
  • Deibler RW, Kirschner MW. Quantitative reconstitution of mitotic CDK1 activation in somatic cell extracts. Mol Cell 2010; 37:753-67. PubMed
  • Wu T, Merbl Y, Huo Y, Gallop JL, Tzur A, Kirschner MW. UBE2S drives elongation of K11-linked ubiquitin chains by the anaphase-promoting complex. Proc Natl Acad Sci U S A 2010; 107:1355-60. PubMed
  • DeLuna A, Springer M, Kirschner MW, Kishony R. Need-based up-regulation of protein levels in response to deletion of their duplicate genes. PLoS Biol. 2010; 8:e1000347. PubMed
  • Yang W, Di Vizio D, Kirchner M, Steen H, Freeman MR. Proteome scale characterization of human S-acylated proteins in lipid raft-enriched and non-raft membranes. Mol Cell Proteomics 2010; 9:54-70. PubMed
  • Goentoro L, Kirschner MW. Evidence that fold-change, and not absolute level, of beta-catenin dictates Wnt signaling. Mol Cell 2009; 36:872-84. PubMed
  • Goentoro L, Shoval O, Kirschner MW, Alon U. The incoherent feedforward loop can provide fold-change detection in gene regulation. Mol Cell 2009; 36:894-9. PubMed
  • Lebensohn AM, Kirschner MW. Activation of the WAVE complex by coincident signals controls actin assembly. Mol Cell 2009; 36:512-24. PubMed
  • Huang SM, Mishina YM, Liu S, Cheung A, Stegmeier F, Michaud GA, Charlat O, Wiellette E, Zhang Y, Wiessner S, Hild M, Shi X, Wilson CJ, Mickanin C, Myer V, Fazal A, Tomlinson R, Serluca F, Shao W, Cheng H, Shultz M, Rau C, Schirle M, Schlegl J, Ghidelli S, Fawell S, Lu C, Curtis D, Kirschner MW, Lengauer C, Finan PM, Tallarico JA, Bouwmeester T, Porter JA, Bauer A, Cong F. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature 2009; 461:614-20. PubMed
  • Tzur A, Kafri R, LeBleu VS, Lahav G, Kirschner MW. Cell growth and size homeostasis in proliferating animal cells. Science 2009; 325:167-71. PubMed
  • Singh S,Springer M,Steen J,Kirschner MW,Steen H. FLEXIQuant: a novel tool for the absolute quantification of proteins, and the simultaneous identification and quantification of potentially modified peptides. J Proteome Res 2009; 8:2201-10. PubMed
  • Merbl Y,Kirschner MW. Large-scale detection of ubiquitination substrates using cell extracts and protein microarrays. Proc Natl Acad Sci U S A 2009; 106:2543-8. PubMed
  • Steen JA, Steen H, Georgi A, Parker K, Springer M, Kirchner M, Hamprecht F, Kirschner MW. Different phosphorylation states of the anaphase promoting complex in response to antimitotic drugs: a quantitative proteomic analysis. Proc Natl Acad Sci U S A 2008; 105:6069-74. PubMed
  • Mor I, Sklan EH, Podoly E, Pick M, Kirschner M, Yogev L, Bar-Sheshet Itach S, Schreiber L, Geyer B, Mor T, Grisaru D, Soreq H. Acetylcholinesterase-R increases germ cell apoptosis but enhances sperm motility. J Cell Mol Med 2008; 12:479-95. PubMed
  • Milo R, Hou JH, Springer M, Brenner MP, Kirschner MW. The relationship between evolutionary and physiological variation in hemoglobin. Proc Natl Acad Sci U S A 2007; 104:16998-7003. PubMed
  • Weiner OD, Marganski WA, Wu LF, Altschuler SJ, Kirschner MW. An actin-based wave generator organizes cell motility. PLoS Biol 2007; 5:e221. PubMed
  • Reddy SK, Rape M, Margansky WA, Kirschner MW. Ubiquitination by the anaphase-promoting complex drives spindle checkpoint inactivation. Nature 2007; 446:921-5. PubMed
  • Stegmeier F, Rape M, Draviam VM, Nalepa G, Sowa ME, Ang XL, McDonald ER, Li MZ, Hannon GJ, Sorger PK, Kirschner MW, Harper JW, Elledge SJ. Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities. Nature 2007; 446:876-81. PubMed
  • Rape M, Reddy SK, Kirschner MW. The processivity of multiubiquitination by the APC determines the order of substrate degradation. Cell 2006; 124:89-103. PubMed
  • Wei W, Ayad NG, Wan Y, Zhang GJ, Kirschner MW, Kaelin WG. Degradation of the SCF component Skp2 in cell-cycle phase G1 by the anaphase-promoting complex. Nature 2004; 428:194-8. PubMed
  • Yan C, Martinez-Quiles N, Eden S, Shibata T, Takeshima F, Shinkura R, Fujiwara Y, Bronson R, Snapper SB, Kirschner MW, Geha R, Rosen FS, Alt FW. WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility. EMBO J 2003; 22:3602-12. 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
  • Zou H, McGarry TJ, Bernal T, Kirschner MW. Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. Science 1999; 285:418-22. PubMed
  • Rohatgi R, Ma L, Miki H, Lopez M, Kirchhausen T, Takenawa T, Kirschner MW. The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly. Cell 1999; 97:221-31. PubMed
  • Ma L, Rohatgi R, Kirschner MW. The Arp2/3 complex mediates actin polymerization induced by the small GTP-binding protein Cdc42. Proc Natl Acad Sci U S A 1998; 95:15362-7. PubMed
  • Fang G, Yu H, Kirschner MW. Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1. Mol Cell 1998; 2:163-71. PubMed
  • Fang G, Yu H, Kirschner MW. The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation. Genes Dev 1998; 12:1871-83. PubMed
  • McGarry TJ, Kirschner MW. Geminin, an inhibitor of DNA replication, is degraded during mitosis. Cell 1998; 93:1043-53. PubMed
  • King RW, Deshaies RJ, Peters JM, Kirschner MW. How proteolysis drives the cell cycle. Science 1996; 274:1652-9. PubMed
  • Lustig KD, Kroll KL, Sun EE, Kirschner MW. Expression cloning of a Xenopus T-related gene (Xombi) involved in mesodermal patterning and blastopore lip formation. Development 1996; 122:4001-12. PubMed
  • Peters JM, King RW, H. Identification of BIME as a subunit of the anaphase-promoting complex. Science 1996; 274:1199-201. PubMed
Hide