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Stephen John Haggarty, Ph.D.

TitleAssociate Professor of Neurology
InstitutionMassachusetts General Hospital
DepartmentNeurology
AddressMassachusetts General Hospital
Richard B. Simches Research Center/CPZN 5.412
185 Cambridge St
Boston MA 02114
Phone617/495-8394

 Mentoring 
 current student opportunities
Available: 10/01/13, Expires: 09/30/15

Students will learn how to generate and characterize neurons and neural progenitor cells derived from patient-specific, induced pluripotent stem cells (iPSCs) using functional genomic tools, including high-content imaging, RNA-seq, and small molecule screening. Stem cell models already generated include Fragile X syndrome, Rett syndrome, Pitt-Hopkins syndrome, Bipolar disorder, Schizophrenia, and Frontotemporal dementia.


 Bibliographic 
 selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Gräff J, Joseph NF, Horn ME, Samiei A, Meng J, Seo J, Rei D, Bero AW, Phan TX, Wagner F, Holson E, Xu J, Sun J, Neve RL, Mach RH, Haggarty SJ, Tsai LH. Epigenetic Priming of Memory Updating during Reconsolidation to Attenuate Remote Fear Memories. Cell. 2014 Jan 16; 156(1-2):261-76.
    View in: PubMed
  2. Wang C, Eessalu TE, Barth VN, Mitch CH, Wagner FF, Hong Y, Neelamegam R, Schroeder FA, Holson EB, Haggarty SJ, Hooker JM. Design, synthesis, and evaluation of hydroxamic acid-based molecular probes for in vivo imaging of histone deacetylase (HDAC) in brain. Am J Nucl Med Mol Imaging. 2013; 4(1):29-38.
    View in: PubMed
  3. Schroeder FA, Lewis MC, Fass DM, Wagner FF, Zhang YL, Hennig KM, Gale J, Zhao WN, Reis S, Barker DD, Berry-Scott E, Kim SW, Clore EL, Hooker JM, Holson EB, Haggarty SJ, Petryshen TL. A Selective HDAC 1/2 Inhibitor Modulates Chromatin and Gene Expression in Brain and Alters Mouse Behavior in Two Mood-Related Tests. PLoS One. 2013; 8(8):e71323.
    View in: PubMed
  4. Schroeder FA, Chonde DB, Riley MM, Moseley CK, Granda ML, Wilson CM, Wagner FF, Zhang YL, Gale J, Holson EB, Haggarty SJ, Hooker JM. FDG-PET imaging reveals local brain glucose utilization is altered by class I histone deacetylase inhibitors. Neurosci Lett. 2013 Aug 29; 550:119-24.
    View in: PubMed
  5. Wang Y, Zhang YL, Hennig K, Gale JP, Hong Y, Cha A, Riley M, Wagner F, Haggarty SJ, Holson E, Hooker J. Class I HDAC imaging using [ (3)H]CI-994 autoradiography. Epigenetics. 2013 Jul 1; 8(7):756-64.
    View in: PubMed
  6. Kennedy PJ, Feng J, Robison AJ, Maze I, Badimon A, Mouzon E, Chaudhury D, Damez-Werno DM, Haggarty SJ, Han MH, Bassel-Duby R, Olson EN, Nestler EJ. Class I HDAC inhibition blocks cocaine-induced plasticity by targeted changes in histone methylation. Nat Neurosci. 2013 Apr; 16(4):434-40.
    View in: PubMed
  7. Shah RR, Koniski A, Shinde M, Blythe SA, Fass DM, Haggarty SJ, Palis J, Klein PS. Regulation of primitive hematopoiesis by class I histone deacetylases. Dev Dyn. 2013 Feb; 242(2):108-21.
    View in: PubMed
  8. Talkowski ME, Maussion G, Crapper L, Rosenfeld JA, Blumenthal I, Hanscom C, Chiang C, Lindgren A, Pereira S, Ruderfer D, Diallo AB, Lopez JP, Turecki G, Chen ES, Gigek C, Harris DJ, Lip V, An Y, Biagioli M, Macdonald ME, Lin M, Haggarty SJ, Sklar P, Purcell S, Kellis M, Schwartz S, Shaffer LG, Natowicz MR, Shen Y, Morton CC, Gusella JF, Ernst C. Disruption of a large intergenic noncoding RNA in subjects with neurodevelopmental disabilities. Am J Hum Genet. 2012 Dec 7; 91(6):1128-34.
    View in: PubMed
  9. Zhao WN, Cheng C, Theriault KM, Sheridan SD, Tsai LH, Haggarty SJ. A high-throughput screen for Wnt/ß-catenin signaling pathway modulators in human iPSC-derived neural progenitors. J Biomol Screen. 2012 Oct; 17(9):1252-63.
    View in: PubMed
  10. Rueckert EH, Barker D, Ruderfer D, Bergen SE, O'Dushlaine C, Luce CJ, Sheridan SD, Theriault KM, Chambert K, Moran J, Purcell SM, Madison JM, Haggarty SJ, Sklar P. Cis-acting regulation of brain-specific ANK3 gene expression by a genetic variant associated with bipolar disorder. Mol Psychiatry. 2013 Aug; 18(8):922-9.
    View in: PubMed
  11. Anguera MC, Sadreyev R, Zhang Z, Szanto A, Payer B, Sheridan SD, Kwok S, Haggarty SJ, Sur M, Alvarez J, Gimelbrant A, Mitalipova M, Kirby JE, Lee JT. Molecular signatures of human induced pluripotent stem cells highlight sex differences and cancer genes. Cell Stem Cell. 2012 Jul 6; 11(1):75-90.
    View in: PubMed
  12. Fass DM, Reis SA, Ghosh B, Hennig KM, Joseph NF, Zhao WN, Nieland TJ, Guan JS, Kuhnle CE, Tang W, Barker DD, Mazitschek R, Schreiber SL, Tsai LH, Haggarty SJ. Crebinostat: a novel cognitive enhancer that inhibits histone deacetylase activity and modulates chromatin-mediated neuroplasticity. Neuropharmacology. 2013 Jan; 64:81-96.
    View in: PubMed
  13. Gräff J, Rei D, Guan JS, Wang WY, Seo J, Hennig KM, Nieland TJ, Fass DM, Kao PF, Kahn M, Su SC, Samiei A, Joseph N, Haggarty SJ, Delalle I, Tsai LH. An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature. 2012 Mar 8; 483(7388):222-6.
    View in: PubMed
  14. Hewitt KJ, Shamis Y, Knight E, Smith A, Maione A, Alt-Holland A, Sheridan SD, Haggarty SJ, Garlick JA. PDGFRß expression and function in fibroblasts derived from pluripotent cells is linked to DNA demethylation. J Cell Sci. 2012 May 1; 125(Pt 9):2276-87.
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  15. Shi P, Scott MA, Ghosh B, Wan D, Wissner-Gross Z, Mazitschek R, Haggarty SJ, Yanik MF. Synapse microarray identification of small molecules that enhance synaptogenesis. Nat Commun. 2011; 2:510.
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  16. Sheridan SD, Theriault KM, Reis SA, Zhou F, Madison JM, Daheron L, Loring JF, Haggarty SJ. Epigenetic characterization of the FMR1 gene and aberrant neurodevelopment in human induced pluripotent stem cell models of fragile X syndrome. PLoS One. 2011; 6(10):e26203.
    View in: PubMed
  17. Marder SR, Roth B, Sullivan PF, Scolnick EM, Nestler EJ, Geyer MA, Welnberger DR, Karayiorgou M, Guidotti A, Gingrich J, Akbarian S, Buchanan RW, Lieberman JA, Conn PJ, Haggarty SJ, Law AJ, Campbell B, Krystal JH, Moghaddam B, Sawa A, Saw A, Caron MG, George SR, Allen JA, Solis M. Advancing drug discovery for schizophrenia. Ann N Y Acad Sci. 2011 Oct; 1236:30-43.
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  18. Wilson AJ, Holson E, Wagner F, Zhang YL, Fass DM, Haggarty SJ, Bhaskara S, Hiebert SW, Schreiber SL, Khabele D. The DNA damage mark pH2AX differentiates the cytotoxic effects of small molecule HDAC inhibitors in ovarian cancer cells. Cancer Biol Ther. 2011 Sep 15; 12(6):484-93.
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  19. Habibi E, Masoudi-Nejad A, Abdolmaleky HM, Haggarty SJ. Emerging roles of epigenetic mechanisms in Parkinson's disease. Funct Integr Genomics. 2011 Dec; 11(4):523-37.
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  20. Kuai L, Ong SE, Madison JM, Wang X, Duvall JR, Lewis TA, Luce CJ, Conner SD, Pearlman DA, Wood JL, Schreiber SL, Carr SA, Scolnick EM, Haggarty SJ. AAK1 identified as an inhibitor of neuregulin-1/ErbB4-dependent neurotrophic factor signaling using integrative chemical genomics and proteomics. Chem Biol. 2011 Jul 29; 18(7):891-906.
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  21. Haggarty SJ, Tsai LH. Probing the role of HDACs and mechanisms of chromatin-mediated neuroplasticity. Neurobiol Learn Mem. 2011 Jul; 96(1):41-52.
    View in: PubMed
  22. Reis SA, Thompson MN, Lee JM, Fossale E, Kim HH, Liao JK, Moskowitz MA, Shaw SY, Dong L, Haggarty SJ, MacDonald ME, Seong IS. Striatal neurons expressing full-length mutant huntingtin exhibit decreased N-cadherin and altered neuritogenesis. Hum Mol Genet. 2011 Jun 15; 20(12):2344-55.
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  23. Pan JQ, Lewis MC, Ketterman JK, Clore EL, Riley M, Richards KR, Berry-Scott E, Liu X, Wagner FF, Holson EB, Neve RL, Biechele TL, Moon RT, Scolnick EM, Petryshen TL, Haggarty SJ. AKT kinase activity is required for lithium to modulate mood-related behaviors in mice. Neuropsychopharmacology. 2011 Jun; 36(7):1397-411.
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  24. Biechele TL, Camp ND, Fass DM, Kulikauskas RM, Robin NC, White BD, Taraska CM, Moore EC, Muster J, Karmacharya R, Haggarty SJ, Chien AJ, Moon RT. Chemical-genetic screen identifies riluzole as an enhancer of Wnt/ß-catenin signaling in melanoma. Chem Biol. 2010 Nov 24; 17(11):1177-82.
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  25. Marcaurelle LA, Comer E, Dandapani S, Duvall JR, Gerard B, Kesavan S, Lee MD, Liu H, Lowe JT, Marie JC, Mulrooney CA, Pandya BA, Rowley A, Ryba TD, Suh BC, Wei J, Young DW, Akella LB, Ross NT, Zhang YL, Fass DM, Reis SA, Zhao WN, Haggarty SJ, Palmer M, Foley MA. An aldol-based build/couple/pair strategy for the synthesis of medium- and large-sized rings: discovery of macrocyclic histone deacetylase inhibitors. J Am Chem Soc. 2010 Dec 1; 132(47):16962-76.
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  26. Samara C, Rohde CB, Gilleland CL, Norton S, Haggarty SJ, Yanik MF. Large-scale in vivo femtosecond laser neurosurgery screen reveals small-molecule enhancer of regeneration. Proc Natl Acad Sci U S A. 2010 Oct 26; 107(43):18342-7.
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  27. Bradner JE, Mak R, Tanguturi SK, Mazitschek R, Haggarty SJ, Ross K, Chang CY, Bosco J, West N, Morse E, Lin K, Shen JP, Kwiatkowski NP, Gheldof N, Dekker J, DeAngelo DJ, Carr SA, Schreiber SL, Golub TR, Ebert BL. Chemical genetic strategy identifies histone deacetylase 1 (HDAC1) and HDAC2 as therapeutic targets in sickle cell disease. Proc Natl Acad Sci U S A. 2010 Jul 13; 107(28):12617-22.
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  28. Bradner JE, West N, Grachan ML, Greenberg EF, Haggarty SJ, Warnow T, Mazitschek R. Chemical phylogenetics of histone deacetylases. Nat Chem Biol. 2010 Mar; 6(3):238-243.
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  29. Kuai L, Wang X, Madison JM, Schreiber SL, Scolnick EM, Haggarty SJ. Chemical genetics identifies small-molecule modulators of neuritogenesis involving neuregulin-1/ErbB4 signaling. ACS Chem Neurosci. 2010 Jan 28; 1(4):325-342.
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  30. Kokel D, Bryan J, Laggner C, White R, Cheung CY, Mateus R, Healey D, Kim S, Werdich AA, Haggarty SJ, Macrae CA, Shoichet B, Peterson RT. Rapid behavior-based identification of neuroactive small molecules in the zebrafish. Nat Chem Biol. 2010 Mar; 6(3):231-237.
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  31. Rihel J, Prober DA, Arvanites A, Lam K, Zimmerman S, Jang S, Haggarty SJ, Kokel D, Rubin LL, Peterson RT, Schier AF. Zebrafish behavioral profiling links drugs to biological targets and rest/wake regulation. Science. 2010 Jan 15; 327(5963):348-51.
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  32. Maze I, Covington HE, Dietz DM, LaPlant Q, Renthal W, Russo SJ, Mechanic M, Mouzon E, Neve RL, Haggarty SJ, Ren Y, Sampath SC, Hurd YL, Greengard P, Tarakhovsky A, Schaefer A, Nestler EJ. Essential role of the histone methyltransferase G9a in cocaine-induced plasticity. Science. 2010 Jan 8; 327(5962):213-6.
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  33. Kilgore M, Miller CA, Fass DM, Hennig KM, Haggarty SJ, Sweatt JD, Rumbaugh G. Inhibitors of class 1 histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer's disease. Neuropsychopharmacology. 2010 Mar; 35(4):870-80.
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  34. Covington HE, Maze I, LaPlant QC, Vialou VF, Ohnishi YN, Berton O, Fass DM, Renthal W, Rush AJ, Wu EY, Ghose S, Krishnan V, Russo SJ, Tamminga C, Haggarty SJ, Nestler EJ. Antidepressant actions of histone deacetylase inhibitors. J Neurosci. 2009 Sep 16; 29(37):11451-60.
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  35. James RG, Biechele TL, Conrad WH, Camp ND, Fass DM, Major MB, Sommer K, Yi X, Roberts BS, Cleary MA, Arthur WT, MacCoss M, Rawlings DJ, Haggarty SJ, Moon RT. Bruton's tyrosine kinase revealed as a negative regulator of Wnt-beta-catenin signaling. Sci Signal. 2009; 2(72):ra25.
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  36. Guan JS, Haggarty SJ, Giacometti E, Dannenberg JH, Joseph N, Gao J, Nieland TJ, Zhou Y, Wang X, Mazitschek R, Bradner JE, DePinho RA, Jaenisch R, Tsai LH. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature. 2009 May 7; 459(7243):55-60.
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  37. Mao Y, Ge X, Frank CL, Madison JM, Koehler AN, Doud MK, Tassa C, Berry EM, Soda T, Singh KK, Biechele T, Petryshen TL, Moon RT, Haggarty SJ, Tsai LH. Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3beta/beta-catenin signaling. Cell. 2009 Mar 20; 136(6):1017-31.
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  38. Rohde CB, Gilleland C, Samara C, Norton S, Haggarty S, Yanik MF. Microfluidic in vivo screen identifies compounds enhancing neuronal regeneration. Conf Proc IEEE Eng Med Biol Soc. 2009; 2009:5950-2.
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  39. Kim D, Frank CL, Dobbin MM, Tsunemoto RK, Tu W, Peng PL, Guan JS, Lee BH, Moy LY, Giusti P, Broodie N, Mazitschek R, Delalle I, Haggarty SJ, Neve RL, Lu Y, Tsai LH. Deregulation of HDAC1 by p25/Cdk5 in neurotoxicity. Neuron. 2008 Dec 10; 60(5):803-17.
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  40. Renthal W, Maze I, Krishnan V, Covington HE, Xiao G, Kumar A, Russo SJ, Graham A, Tsankova N, Kippin TE, Kerstetter KA, Neve RL, Haggarty SJ, McKinsey TA, Bassel-Duby R, Olson EN, Nestler EJ. Histone deacetylase 5 epigenetically controls behavioral adaptations to chronic emotional stimuli. Neuron. 2007 Nov 8; 56(3):517-29.
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  41. Schmitz K, Haggarty SJ, McPherson OM, Clardy J, Koehler AN. Detecting binding interactions using microarrays of natural product extracts. J Am Chem Soc. 2007 Sep 19; 129(37):11346-7.
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  42. Lamb J, Crawford ED, Peck D, Modell JW, Blat IC, Wrobel MJ, Lerner J, Brunet JP, Subramanian A, Ross KN, Reich M, Hieronymus H, Wei G, Armstrong SA, Haggarty SJ, Clemons PA, Wei R, Carr SA, Lander ES, Golub TR. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science. 2006 Sep 29; 313(5795):1929-35.
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  43. Perlstein EO, Ruderfer DM, Ramachandran G, Haggarty SJ, Kruglyak L, Schreiber SL. Revealing complex traits with small molecules and naturally recombinant yeast strains. Chem Biol. 2006 Mar; 13(3):319-27.
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  44. Forman JJ, Clemons PA, Schreiber SL, Haggarty SJ. SpectralNET--an application for spectral graph analysis and visualization. BMC Bioinformatics. 2005; 6:260.
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  45. Haggarty SJ. The principle of complementarity: chemical versus biological space. Curr Opin Chem Biol. 2005 Jun; 9(3):296-303.
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  46. Huang J, Zhu H, Haggarty SJ, Spring DR, Hwang H, Jin F, Snyder M, Schreiber SL. Finding new components of the target of rapamycin (TOR) signaling network through chemical genetics and proteome chips. Proc Natl Acad Sci U S A. 2004 Nov 23; 101(47):16594-9.
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  47. Haggarty SJ, Clemons PA, Wong JC, Schreiber SL. Mapping chemical space using molecular descriptors and chemical genetics: deacetylase inhibitors. Comb Chem High Throughput Screen. 2004 Nov; 7(7):669-76.
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  48. Wagner BK, Haggarty SJ, Clemons PA. Chemical genomics: probing protein function using small molecules. Am J Pharmacogenomics. 2004; 4(5):313-20.
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  49. Haggarty SJ, Koeller KM, Kau TR, Silver PA, Roberge M, Schreiber SL. Small molecule modulation of the human chromatid decatenation checkpoint. Chem Biol. 2003 Dec; 10(12):1267-79.
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  50. Haggarty SJ, Clemons PA, Schreiber SL. Chemical genomic profiling of biological networks using graph theory and combinations of small molecule perturbations. J Am Chem Soc. 2003 Sep 3; 125(35):10543-5.
    View in: PubMed
  51. Haggarty SJ, Koeller KM, Wong JC, Butcher RA, Schreiber SL. Multidimensional chemical genetic analysis of diversity-oriented synthesis-derived deacetylase inhibitors using cell-based assays. Chem Biol. 2003 May; 10(5):383-96.
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  52. Koeller KM, Haggarty SJ, Perkins BD, Leykin I, Wong JC, Kao MC, Schreiber SL. Chemical genetic modifier screens: small molecule trichostatin suppressors as probes of intracellular histone and tubulin acetylation. Chem Biol. 2003 May; 10(5):397-410.
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  53. Haggarty SJ, Koeller KM, Wong JC, Grozinger CM, Schreiber SL. Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc Natl Acad Sci U S A. 2003 Apr 15; 100(8):4389-94.
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  54. Haggarty SJ, Mayer TU, Miyamoto DT, Fathi R, King RW, Mitchison TJ, Schreiber SL. Dissecting cellular processes using small molecules: identification of colchicine-like, taxol-like and other small molecules that perturb mitosis. Chem Biol. 2000 Apr; 7(4):275-86.
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  55. Haggarty SJ, Ramalho-Santos M. Will cell alliance breed bureaucracy and leave contributors out? Nature. 2000 Feb 10; 403(6770):591.
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  56. Mayer TU, Kapoor TM, Haggarty SJ, King RW, Schreiber SL, Mitchison TJ. Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science. 1999 Oct 29; 286(5441):971-4.
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  57. Stockwell BR, Haggarty SJ, Schreiber SL. High-throughput screening of small molecules in miniaturized mammalian cell-based assays involving post-translational modifications. Chem Biol. 1999 Feb; 6(2):71-83.
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  58. Roberge M, Berlinck RG, Xu L, Anderson HJ, Lim LY, Curman D, Stringer CM, Friend SH, Davies P, Vincent I, Haggarty SJ, Kelly MT, Britton R, Piers E, Andersen RJ. High-throughput assay for G2 checkpoint inhibitors and identification of the structurally novel compound isogranulatimide. Cancer Res. 1998 Dec 15; 58(24):5701-6.
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