Stuart Schreiber

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. pmc Gold(I)-catalyzed coupling reactions for the synthesis of diverse small molecules using the build/couple/pair strategy
    Tuoping Luo
    Howard Hughes Medical Institute, Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    J Am Chem Soc 131:5667-74. 2009
  2. pmc Discovery of small-molecule modulators of the Sonic Hedgehog pathway
    Giannina I Schaefer
    Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA
    J Am Chem Soc 135:9675-80. 2013
  3. pmc Copper-mediated amidation of heterocyclic and aromatic C-H bonds
    Qiu Wang
    Howard Hughes Medical Institute, Broad Institute, Cambridge, Massachusetts 02142, USA
    Org Lett 11:5178-80. 2009
  4. pmc Diversity synthesis of complex pyridines yields a probe of a neurotrophic signaling pathway
    B Lawrence Gray
    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA
    Org Lett 10:2621-4. 2008
  5. pmc Distinct biological network properties between the targets of natural products and disease genes
    Vlado Dancik
    Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, Massachusetts 02143, USA
    J Am Chem Soc 132:9259-61. 2010
  6. pmc Stereochemical and skeletal diversity arising from amino propargylic alcohols
    Daniela Pizzirani
    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA
    Org Lett 12:2822-5. 2010
  7. pmc Skeletally diverse small molecules using a build/couple/pair strategy
    Takuya Uchida
    Howard Hughes Medical Institute, Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Org Lett 11:1559-62. 2009
  8. pmc Expanding stereochemical and skeletal diversity using petasis reactions and 1,3-dipolar cycloadditions
    Giovanni Muncipinto
    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, United States
    Org Lett 12:5230-3. 2010
  9. pmc A small-molecule probe of the histone methyltransferase G9a induces cellular senescence in pancreatic adenocarcinoma
    Yuan Yuan
    Chemical Biology Program, Broad Institute, Cambridge, Massachusetts 02142, United States
    ACS Chem Biol 7:1152-7. 2012
  10. pmc Syntheses of α-pyrones using gold-catalyzed coupling reactions
    Tuoping Luo
    Howard Hughes Medical Institute, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, United States
    Org Lett 13:2834-6. 2011

Research Grants

Detail Information

Publications86

  1. pmc Gold(I)-catalyzed coupling reactions for the synthesis of diverse small molecules using the build/couple/pair strategy
    Tuoping Luo
    Howard Hughes Medical Institute, Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    J Am Chem Soc 131:5667-74. 2009
    ..These pairing reactions include one based on a novel aza-Wittig-6pi-electrocyclization sequence and others based on ring-closing metathesis reactions...
  2. pmc Discovery of small-molecule modulators of the Sonic Hedgehog pathway
    Giannina I Schaefer
    Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA
    J Am Chem Soc 135:9675-80. 2013
    ..Yet, in other ways their mechanism-of-action is strikingly distinct. We hope that these novel compounds will be useful probes of this complex signaling pathway. ..
  3. pmc Copper-mediated amidation of heterocyclic and aromatic C-H bonds
    Qiu Wang
    Howard Hughes Medical Institute, Broad Institute, Cambridge, Massachusetts 02142, USA
    Org Lett 11:5178-80. 2009
    ..These reactions provide efficient access to many biologically important skeletons, including ones with the potential to serve as inhibitors of HMTs...
  4. pmc Diversity synthesis of complex pyridines yields a probe of a neurotrophic signaling pathway
    B Lawrence Gray
    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA
    Org Lett 10:2621-4. 2008
    ..30 microM) in a screen that probes a pathway likely to be involved in breast cancers and schizophrenia...
  5. pmc Distinct biological network properties between the targets of natural products and disease genes
    Vlado Dancik
    Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, Massachusetts 02143, USA
    J Am Chem Soc 132:9259-61. 2010
    ..This result also suggests that additional sources of small molecules will be required to discover drugs targeting the root causes of human disease in the future...
  6. pmc Stereochemical and skeletal diversity arising from amino propargylic alcohols
    Daniela Pizzirani
    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA
    Org Lett 12:2822-5. 2010
    ..The change in shape brought about by different intramolecular cyclizations of diastereoisomeric amino propargylic alcohols is quantified using principal moment-of-inertia (PMI) shape analysis...
  7. pmc Skeletally diverse small molecules using a build/couple/pair strategy
    Takuya Uchida
    Howard Hughes Medical Institute, Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Org Lett 11:1559-62. 2009
    ..The synthetic pathway yields products having 12 different skeletons using only three steps and has the potential to enable substantial stereochemical diversification in the future...
  8. pmc Expanding stereochemical and skeletal diversity using petasis reactions and 1,3-dipolar cycloadditions
    Giovanni Muncipinto
    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, United States
    Org Lett 12:5230-3. 2010
    ..The change in shape of previous compounds and those in this study is quantified and compared using principal moment-of-inertia shape analysis...
  9. pmc A small-molecule probe of the histone methyltransferase G9a induces cellular senescence in pancreatic adenocarcinoma
    Yuan Yuan
    Chemical Biology Program, Broad Institute, Cambridge, Massachusetts 02142, United States
    ACS Chem Biol 7:1152-7. 2012
    ..ATM-pathway activation, caused by either genetic or small-molecule inhibition of G9a, may mediate BRD4770-induced cell senescence. BRD4770 may be a useful tool to study G9a and its role in senescence and cancer cell biology...
  10. pmc Syntheses of α-pyrones using gold-catalyzed coupling reactions
    Tuoping Luo
    Howard Hughes Medical Institute, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, United States
    Org Lett 13:2834-6. 2011
    ..Novel cascade reactions involving propiolic acids are reported that give rise to α-pyrones with different substitution patterns...
  11. pmc Multilevel regulation of growth rate in yeast revealed using systems biology
    Arvind Ramanathan
    The Broad Institute of Harvard and MIT, Chemical Biology Program, 7 Cambridge Center, Cambridge, MA 02142, USA
    J Biol 6:3. 2007
    ..Measurements made under varying nutrient conditions, corresponding to biochemical pathways that correlate primarily with growth rate, reveal a central role for mitochondrial metabolism and the TOR (target of rapamycin) signaling pathway...
  12. pmc Global nucleosome occupancy in yeast
    Bradley E Bernstein
    Department of Chemistry and Chemical Biology, Bauer Center for Genomics Research, and Howard Hughes Medical Institute, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
    Genome Biol 5:R62. 2004
    ..We systematically evaluated nucleosome occupancy in yeast promoters by immunoprecipitating nucleosomal DNA and quantifying enrichment by microarrays...
  13. pmc SpectralNET--an application for spectral graph analysis and visualization
    Joshua J Forman
    The Broad Institute of MIT and Harvard University, Cambridge, MA 02141, USA
    BMC Bioinformatics 6:260. 2005
    ..SpectralNET is a flexible application for analyzing and visualizing these biological and chemical networks...
  14. pmc Organic synthesis toward small-molecule probes and drugs
    Stuart L Schreiber
    Howard Hughes Medical Institute, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 108:6699-702. 2011
    ..This perspective article describes new roles that modern organic chemistry will need to play in overcoming this challenge...
  15. ncbi request reprint Small molecules: the missing link in the central dogma
    Stuart L Schreiber
    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA
    Nat Chem Biol 1:64-6. 2005
    ..Small molecules have critical roles at all levels of biological complexity and yet remain orphans of the central dogma. Chemical biologists, working with small molecules, expand our understanding of these central elements of life...
  16. ncbi request reprint Dissecting glucose signalling with diversity-oriented synthesis and small-molecule microarrays
    Finny G Kuruvilla
    Howard Hughes Medical Institute, Institute for Chemistry and Cell Biology, Bauer Center for Genomics Research, Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138, USA
    Nature 416:653-7. 2002
    ....
  17. ncbi request reprint Multidimensional chemical genetic analysis of diversity-oriented synthesis-derived deacetylase inhibitors using cell-based assays
    Stephen J Haggarty
    Departments of Molecular and Cellular Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
    Chem Biol 10:383-96. 2003
    ..These small molecules will facilitate dissecting the role of acetylation in a variety of cell biological processes...
  18. pmc Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation
    Stephen J Haggarty
    Department of Molecular and Cellular Biology, and Harvard Institute of Chemistry and Cell Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 100:4389-94. 2003
    ..They also suggest that small molecules that selectively inhibit HDAC6-mediated alpha-tubulin deacetylation, a first example of which is tubacin, might have therapeutic applications as antimetastatic and antiangiogenic agents...
  19. ncbi request reprint Identifying biologically active compound classes using phenotypic screening data and sampling statistics
    Justin Klekota
    Howard Hughes Medical Institute, Harvard Institute of Chemistry and Cell Biology, Broad Institute of Harvard and MIT, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA
    J Chem Inf Model 45:1824-36. 2005
    ..In addition, many weak and potentially novel classes of active compounds, overlooked by individual assay measurements, were suggested...
  20. pmc Vector algebra in the analysis of genome-wide expression data
    Finny G Kuruvilla
    Howard Hughes Medical Institute, Bauer Center for Genomics Research, Department of Chemistry, Harvard University, Cambridge, MA 02138, USA
    Genome Biol 3:RESEARCH0011. 2002
    ..In particular, concepts from vector algebra have proven useful in the study of genome-wide expression data...
  21. pmc Single-nucleosome mapping of histone modifications in S. cerevisiae
    Chih Long Liu
    Bauer Center for Genomics Research, Harvard University, Cambridge, Massachusetts, USA
    PLoS Biol 3:e328. 2005
    ..g., promoter nucleosomes) from those at another location (e.g., over the 3' ends of coding regions). These results are consistent with the idea of a simple, redundant histone code, in which multiple modifications share the same role...
  22. pmc Methylation of histone H3 Lys 4 in coding regions of active genes
    Bradley E Bernstein
    Department of Chemistry and Chemical Biology and The Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 99:8695-700. 2002
    ..In the context of recent studies showing that Lys 4 methylation precludes histone deacetylase recruitment, we conclude that Set1 facilitates transcription, in part, by protecting active coding regions from deacetylation...
  23. ncbi request reprint Genomic maps and comparative analysis of histone modifications in human and mouse
    Bradley E Bernstein
    Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
    Cell 120:169-81. 2005
    ..This suggests that the DNA elements that direct the methylation represent only a small fraction of the region or lie at some distance from the site...
  24. ncbi request reprint Mapping chemical space using molecular descriptors and chemical genetics: deacetylase inhibitors
    Stephen J Haggarty
    The Eli and Edythe L Broad Institute, Massachusetts Institute of Technology and Harvard University, 320 Charles Street, Cambridge, MA 02141, USA
    Comb Chem High Throughput Screen 7:669-76. 2004
    ..Similar analyses of other chemical spaces and activity classes promise to facilitate the development of chemical genetics...
  25. ncbi request reprint Microarray-based method for monitoring yeast overexpression strains reveals small-molecule targets in TOR pathway
    Rebecca A Butcher
    Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA
    Nat Chem Biol 2:103-9. 2006
    ....
  26. pmc Disease allele-dependent small-molecule sensitivities in blood cells from monogenic diabetes
    Stanley Y Shaw
    Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 108:492-7. 2011
    ..This method may suggest therapeutic hypotheses for other nonblood disorders...
  27. ncbi request reprint Rpd3p relocation mediates a transcriptional response to rapamycin in yeast
    Emily L Humphrey
    Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, 12 Oxford Street, Cambridge, MA 02138, USA
    Chem Biol 11:295-9. 2004
    ..Rather, the comprehensive analysis presented here strongly supports a model in which recruitment of Rpd3p to gene promoters is a regulated step in the control of gene repression...
  28. pmc Amino acid metabolic origin as an evolutionary influence on protein sequence in yeast
    Benjamin L de Bivort
    Rowland Institute at Harvard, Harvard University, 100 Edwin Land Boulevard, Cambridge, MA 02142, USA
    J Mol Evol 68:490-7. 2009
    ..This trend is strongest in ancient proteins, suggesting that oscillating endogenous amino acid availability exerted genome-wide selective pressure on protein sequences across evolutionary time...
  29. pmc Development and validation of a T7 based linear amplification for genomic DNA
    Chih Long Liu
    Department of Chemistry and Chemical Biology, and Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA
    BMC Genomics 4:19. 2003
    ..These protocols have yet to be applied to the analysis of genomic DNA due to the lack of a suitable tag such as the polyA tail...
  30. doi request reprint Small-molecule fluorophores to detect cell-state switching in the context of high-throughput screening
    Bridget K Wagner
    Chemical Biology Program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA
    J Am Chem Soc 130:4208-9. 2008
    ..We suggest that the strategy of screening for screening agents reported here may be extended more broadly in the future...
  31. ncbi request reprint Evolutionarily conserved optimization of amino acid biosynthesis
    Ethan O Perlstein
    Howard Hughes Medical Institute, Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA
    J Mol Evol 65:186-96. 2007
    ....
  32. pmc Quantifying fitness distributions and phenotypic relationships in recombinant yeast populations
    Ethan O Perlstein
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 104:10553-8. 2007
    ..This analysis allows us to evaluate and to gain better theoretical understanding of the costs and benefits of sex in the F1 generation...
  33. ncbi request reprint Signaling network model of chromatin
    Stuart L Schreiber
    Department of Chemistry and Chemical Biology and Howard Hughes Medical Institute, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
    Cell 111:771-8. 2002
    ..This view provides insight into chromatin function and epigenetic inheritance...
  34. ncbi request reprint A microarray-based protocol for monitoring the growth of yeast overexpression strains
    Rebecca A Butcher
    Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA
    Nat Protoc 1:569-76. 2006
    ..This protocol can be completed in approximately 15 hours of hands-on time over the course of several days...
  35. ncbi request reprint Revealing complex traits with small molecules and naturally recombinant yeast strains
    Ethan O Perlstein
    Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA
    Chem Biol 13:319-27. 2006
    ..The systematic combination of natural variants of yeast and small molecules that modulate evolutionarily conserved cellular processes can enable a better understanding of the general features of complex traits...
  36. pmc ChemBank: a small-molecule screening and cheminformatics resource database
    Kathleen Petri Seiler
    Chemical Biology Program and Platform, Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA
    Nucleic Acids Res 36:D351-9. 2008
    ..The goal of ChemBank is to provide life scientists unfettered access to biomedically relevant data and tools heretofore available primarily in the private sector...
  37. ncbi request reprint Query Chem: a Google-powered web search combining text and chemical structures
    Justin Klekota
    Howard Hughes Medical Institute 12 Oxford Street, Cambridge, MA 02138, USA
    Bioinformatics 22:1670-3. 2006
    ..Furthermore, a structure can be combined with textual query terms to further restrict searches. Query Chem's search results can retrieve many interesting structure-property relationships of biomolecules on the Web...
  38. ncbi request reprint Genetic basis of individual differences in the response to small-molecule drugs in yeast
    Ethan O Perlstein
    Howard Hughes Medical Institute, Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nat Genet 39:496-502. 2007
    ..Our results provide a step toward a systematic understanding of small-molecule drug action in genetically distinct individuals...
  39. ncbi request reprint The use of chromatin immunoprecipitation assays in genome-wide analyses of histone modifications
    Bradley E Bernstein
    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA
    Methods Enzymol 376:349-60. 2004
  40. pmc Finding new components of the target of rapamycin (TOR) signaling network through chemical genetics and proteome chips
    Jing Huang
    Howard Hughes Medical Institute, Harvard Institute of Chemistry and Cell Biology, and Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 101:16594-9. 2004
    ..Our results illustrate the combined use of chemical genetics and proteomics in biological discovery and map a path for creating useful therapeutics for treating human diseases involving the TOR pathway, such as diabetes and cancer...
  41. ncbi request reprint Chemical genetic modifier screens: small molecule trichostatin suppressors as probes of intracellular histone and tubulin acetylation
    Kathryn M Koeller
    Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
    Chem Biol 10:397-410. 2003
    ..Small molecule suppressors such as the ITSAs, available from chemical genetic suppressor screens, may prove to be valuable probes of many biological processes...
  42. pmc Identification of Ald6p as the target of a class of small-molecule suppressors of FK506 and their use in network dissection
    Rebecca A Butcher
    Department of Chemistry and Chemical Biology and Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 101:7868-73. 2004
    ....
  43. ncbi request reprint Integration of growth factor and nutrient signaling: implications for cancer biology
    Alykhan F Shamji
    Harvard Biophysics Program, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
    Mol Cell 12:271-80. 2003
    ..Finally, we describe how the small molecule rapamycin, which inhibits TOR and thereby the activation of these effectors, could be useful to treat tumors that have become dependent upon this pathway for growth...
  44. ncbi request reprint A small molecule suppressor of FK506 that targets the mitochondria and modulates ionic balance in Saccharomyces cerevisiae
    Rebecca A Butcher
    Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
    Chem Biol 10:521-31. 2003
    ..Our data link ionic balance to mitochondrial function and suggest a role for calcineurin in mediating this signaling network...
  45. ncbi request reprint ATR is not required for p53 activation but synergizes with p53 in the replication checkpoint
    Paul Nghiem
    Department of Chemistry, Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA
    J Biol Chem 277:4428-34. 2002
    ..We conclude that ATR and p53 can function independently but that loss of both leads to synergistic disruption of the replication checkpoint...
  46. ncbi request reprint Structural biasing elements for in-cell histone deacetylase paralog selectivity
    Jason C Wong
    Department of Chemistry and Chemical Biology, Harvard Institute of Chemistry and Cell Biology, and the Howard Hughes Medical Institute, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA
    J Am Chem Soc 125:5586-7. 2003
    ..We also show that suberoylanilide hydroxamic acid (SAHA) alone is a nonparalog-selective HDAC inhibitor and that the 1,3-dioxane diversity appended to SAHA is essential for HDAC6 paralog selectivity...
  47. ncbi request reprint Chemical genomic profiling of biological networks using graph theory and combinations of small molecule perturbations
    Stephen J Haggarty
    Departments of Chemistry and Chemical Biology and of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard Institute of Chemistry and Cell Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
    J Am Chem Soc 125:10543-5. 2003
    ..This application of small molecules could be useful for discerning the molecular basis of highly complex biological phenotypes, including those involved in the susceptibility to or etiology of human disease...
  48. ncbi request reprint Deacetylase enzymes: biological functions and the use of small-molecule inhibitors
    Christina M Grozinger
    Department of Chemistry and Chemical Biology and, Howard Hughes Medical Institute, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
    Chem Biol 9:3-16. 2002
  49. ncbi request reprint Relationship of stereochemical and skeletal diversity of small molecules to cellular measurement space
    Young Kwon Kim
    Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, and The Eli and Edythe Broad Institute, Program in Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
    J Am Chem Soc 126:14740-5. 2004
    ..These studies illustrate a quantitative method for measuring stereochemical and skeletal diversity of small molecules and their cellular consequences...
  50. ncbi request reprint Global approaches to chromatin
    Bradley E Bernstein
    Department of Chemistry and Chemical Biology, Bauer Center for Genomics Research and the Howard Hughes Medical Institute, Harvard University, 02138, Cambridge, MA, USA
    Chem Biol 9:1167-73. 2002
  51. ncbi request reprint Synthesis of calcineurin-resistant derivatives of FK506 and selection of compensatory receptors
    Paul A Clemons
    Howard Hughes Medical Institute at Harvard University, Cambridge, MA 02138, USA
    Chem Biol 9:49-61. 2002
    ..This new use of the "bump-hole" strategy protects target cells from complications arising from the inhibition of endogenous calcineurin...
  52. pmc Large-scale chemical dissection of mitochondrial function
    Bridget K Wagner
    Broad Institute of Massachusetts Institute of Technology and Harvard, Seven Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nat Biotechnol 26:343-51. 2008
    ..Our screening compendium can be used as a discovery tool both for understanding mitochondrial biology and toxicity and for identifying novel therapeutics...
  53. doi request reprint A small molecule that directs differentiation of human ESCs into the pancreatic lineage
    Shuibing Chen
    Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, Massachusetts, USA
    Nat Chem Biol 5:258-65. 2009
    ..This study describes a chemical screening platform to investigate human ESC differentiation and demonstrates the generation of a cell population that is a key milepost on the path to making beta cells...
  54. pmc Perturbational profiling of nanomaterial biologic activity
    Stanley Y Shaw
    Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 105:7387-92. 2008
    ..These data suggest a strategy of multidimensional characterization of nanomaterials in vitro that can inform the design of novel nanomaterials and guide studies of in vivo activity...
  55. ncbi request reprint Small molecules efficiently direct endodermal differentiation of mouse and human embryonic stem cells
    Malgorzata Borowiak
    Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA
    Cell Stem Cell 4:348-58. 2009
    ..The application of small molecules to differentiate mouse and human ESCs into endoderm represents a step toward achieving a reproducible and efficient production of desired ESC derivatives...
  56. ncbi request reprint Using genome-wide transcriptional profiling to elucidate small-molecule mechanism
    Rebecca A Butcher
    Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA
    Curr Opin Chem Biol 9:25-30. 2005
    ..Transcriptional profiling can also be used to assess a small molecule's specificity for its target and to facilitate analysis of pathways downstream of the target...
  57. ncbi request reprint Identification of a small-molecule inhibitor of class Ia PI3Ks with cell-based screening
    Jiong Yang
    Howard Hughes Medical Institute, Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA
    Chem Biol 14:371-7. 2007
    ..This study illustrates the power of unbiased, phenotypic screening as a means for illuminating cell circuitry, and resulted in the identification of a chemotype for selective inhibition of the class Ia PI3Ks...
  58. pmc Empirical Bayes analysis of quantitative proteomics experiments
    Adam A Margolin
    Cancer Program, The Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
    PLoS ONE 4:e7454. 2009
    ....
  59. ncbi request reprint Small molecules, big players: the National Cancer Institute's Initiative for Chemical Genetics
    Nicola Tolliday
    Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
    Cancer Res 66:8935-42. 2006
    ..This report outlines how the ICG functions, how researchers can take advantage of its screening, chemistry and informatic capabilities, and provides a brief summary of some of the many important research findings...
  60. pmc Small molecules of different origins have distinct distributions of structural complexity that correlate with protein-binding profiles
    Paul A Clemons
    Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 107:18787-92. 2010
    ..Because binding proteins selectively can be a key feature of high-value probes and drugs, synthesizing compounds having features identified in this study may result in improved performance of screening collections...
  61. pmc Direct control of mitochondrial function by mTOR
    Arvind Ramanathan
    Chemical Biology Program, Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 106:22229-32. 2009
    ....
  62. ncbi request reprint Discovery of an inhibitor of a transcription factor using small molecule microarrays and diversity-oriented synthesis
    Angela N Koehler
    Department of Chemistry and Chemical Biology, Harvard Biophysics Program, Howard Hughes Medical Institute, Harvard Institute of Chemistry and Cell Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA
    J Am Chem Soc 125:8420-1. 2003
    ..These results demonstrate that a small molecule discovered using the small molecule microarray binding assay can permeate yeast cells and reach its target transcription factor protein in cells...
  63. pmc Chemical genetic strategy identifies histone deacetylase 1 (HDAC1) and HDAC2 as therapeutic targets in sickle cell disease
    James E Bradner
    Broad Institute of Harvard and Massachusetts Institute Technology, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 107:12617-22. 2010
    ..Our findings suggest the potential of isoform-selective inhibitors of HDAC1 and HDAC2 for the treatment of sickle cell disease...
  64. ncbi request reprint Modular synthesis and preliminary biological evaluation of stereochemically diverse 1,3-dioxanes
    Jason C Wong
    Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
    Chem Biol 11:1279-91. 2004
    ..This evaluation of a portion of the 1,3-dioxane library suggests that many additional probes for chemical genetics will be identified as the entire library becomes biologically annotated...
  65. pmc FKBP12-rapamycin-associated protein associates with mitochondria and senses osmotic stress via mitochondrial dysfunction
    Bimal N Desai
    Department of Chemistry and Chemical Biology, Harvard University, Immunology Program, Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:4319-24. 2002
    ..This module allows the cell to integrate a variety of stress signals that affect mitochondrial function and regulate a growth checkpoint involving p70 S6 kinase...
  66. pmc Identifying the proteins to which small-molecule probes and drugs bind in cells
    Shao En Ong
    Proteomics Platform, The Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 106:4617-22. 2009
    ..Here, we describe in full detail the application of the method to identify targets of kinase inhibitors and immunophilin binders...
  67. ncbi request reprint Ligand design by a combinatorial approach based on modeling and experiment: application to HLA-DR4
    Erik Evensen
    Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA, USA
    J Comput Aided Mol Des 21:395-418. 2007
    ..Computational model building suggest that at least one of the ligands designed and identified by the methods described binds in a mode similar to that of native peptides...
  68. ncbi request reprint Generating diverse skeletons of small molecules combinatorially
    Martin D Burke
    Department of Chemistry and Chemical Biology, Howard Hughes Medical Institute, Institute of Chemistry and Cell Biology, Harvard University, Cambridge, MA 02138, USA
    Science 302:613-8. 2003
    ..A split-pool synthesis of more than 1000 compounds produced overlapping, combinatorial matrices of molecular skeletons and appended building blocks in both enantiomeric and diastereomeric forms...
  69. doi request reprint Small-molecule reagents for cellular pull-down experiments
    Xiang Wang
    Howard Hughes Medical Institute, Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA
    Bioconjug Chem 19:585-7. 2008
    ..This method comprises one element of a systematic approach to the target identification problem in chemical biology...
  70. pmc Towards the optimal screening collection: a synthesis strategy
    Thomas E Nielsen
    Department of Chemistry and Chemical Biology, Harvard University, Howard Hughes Medical Institute, Cambridge, MA 02142, USA
    Angew Chem Int Ed Engl 47:48-56. 2008
    ..Although this transformative chemistry remains elusive, progress is being made. Herein, we review a newly emerging strategy in diversity-oriented small-molecule synthesis that may have the potential to achieve these challenging goals...
  71. pmc Fluorous-based small-molecule microarrays for the discovery of histone deacetylase inhibitors
    Arturo J Vegas
    Howard Hughes Medical Institute, Chemistry and Chemical Biology, Harvard University, Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA
    Angew Chem Int Ed Engl 46:7960-4. 2007
  72. ncbi request reprint Small molecule modulation of the human chromatid decatenation checkpoint
    Stephen J Haggarty
    Department of Molecular Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
    Chem Biol 10:1267-79. 2003
    ..The suptopins provide new molecular tools for dissecting the role of topoisomerases in maintaining genomic stability and determining whether inhibiting the chromatid decatenation checkpoint sensitizes tumor cells to chemotherapeutics...
  73. ncbi request reprint A bivalent chromatin structure marks key developmental genes in embryonic stem cells
    Bradley E Bernstein
    Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Cell 125:315-26. 2006
    ..These results highlight the importance of DNA sequence in defining the initial epigenetic landscape and suggest a novel chromatin-based mechanism for maintaining pluripotency...
  74. ncbi request reprint Active genes are tri-methylated at K4 of histone H3
    Helena Santos-Rosa
    Wellcome Trust Cancer Research UK Institute and Department of Pathology, Tennis Court Road, Cambridge, CB2 1QR, UK
    Nature 419:407-11. 2002
    ..These findings establish the concept of methyl status as a determinant for gene activity and thus extend considerably the complexity of histone modifications...
  75. pmc Histone variant H2A.Z marks the 5' ends of both active and inactive genes in euchromatin
    Ryan M Raisner
    Department of Biochemistry and Biophysics, University of California, 600 16th Street, San Francisco, California 94143, USA
    Cell 123:233-48. 2005
    ..Efficient deposition of H2A.Z is further promoted by a specific pattern of histone H3 and H4 tail acetylation and the bromodomain protein Bdf1, a component of the Swr1 remodeling complex that deposits H2A.Z...
  76. ncbi request reprint SIR1, an upstream component in auxin signaling identified by chemical genetics
    Yunde Zhao
    Section of Cell and Developmental Biology, Division of Biological Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0116, USA
    Science 301:1107-10. 2003
    ..We suggest a molecular context for how the auxin signal is propagated to exert its biological effects...
  77. ncbi request reprint Methylation of histone H3 K4 mediates association of the Isw1p ATPase with chromatin
    Helena Santos-Rosa
    Wellcome Trust Cancer Research UK Institute and Department of Pathology, Tennis Court Road, Cambridge CB2 1QR, United Kingdom
    Mol Cell 12:1325-32. 2003
    ..These results indicate that K4 H3 methylation and Isw1p ATPase activity are intimately linked in regulating transcription of certain genes in yeast...
  78. pmc Small molecules enhance autophagy and reduce toxicity in Huntington's disease models
    Sovan Sarkar
    Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2XY, UK
    Nat Chem Biol 3:331-8. 2007
    ..Thus, we have demonstrated proof of principle for a new approach for discovery of small-molecule modulators of mammalian autophagy...
  79. ncbi request reprint From knowing to controlling: a path from genomics to drugs using small molecule probes
    Robert L Strausberg
    Cancer Genomics Office, National Cancer Institute, 31 Center Drive, Bethesda, MD 20892, USA
    Science 300:294-5. 2003
    ..The information generated with such tools should provide a critical link from genomic discovery to drug development...
  80. ncbi request reprint Stuart Schreiber: biology from a chemist's perspective. Interview by Joanna Owens
    Stuart L Schreiber
    Drug Discov Today 9:299-303. 2004
    ..He was also founding editor of the journal Chemistry & Biology, which is now in its tenth year of publication...
  81. pmc Identification of novel epoxide inhibitors of hepatitis C virus replication using a high-throughput screen
    Lee F Peng
    GI Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA
    Antimicrob Agents Chemother 51:3756-9. 2007
    ..5 microM). We then synthesized an analog of these compounds with optimized activity...
  82. ncbi request reprint Small molecule enhancers of rapamycin-induced TOR inhibition promote autophagy, reduce toxicity in Huntington's disease models and enhance killing of mycobacteria by macrophages
    R Andres Floto
    Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge, UK
    Autophagy 3:620-2. 2007
    ..These SMERs also protected against mutant huntingtin fragment toxicity in Drosophila. We have subsequently tested two of the SMERs in models of tuberculosis and both enhance the killing of mycobacteria by primary human macrophages...
  83. ncbi request reprint Chemical suppression of a genetic mutation in a zebrafish model of aortic coarctation
    Randall T Peterson
    Nat Biotechnol 22:595-9. 2004
    ..Thus, organism-based screens allow the discovery of small molecules that ameliorate complex dysmorphic syndromes even without targeting the affected gene directly...
  84. ncbi request reprint A robust small-molecule microarray platform for screening cell lysates
    James E Bradner
    Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Chem Biol 13:493-504. 2006
    ..We believe that this expanded research capability has considerable promise in biology and medicine...
  85. pmc Total synthesis and biological mode of action of largazole: a potent class I histone deacetylase inhibitor
    Albert Bowers
    Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, USA
    J Am Chem Soc 130:11219-22. 2008
    ....

Research Grants29

  1. STUDIES OF MATERIALS WITH PHYSIOLOGICAL PROPERTIES
    Stuart L Schreiber; Fiscal Year: 2010
    ..Such small molecules will be used to probe the consequences of modulating key mediators of the processes in order to gain a better understanding of their medical potential as targets for novel therapeutics. ..
  2. Versatile diversity-oriented small molecule libraries for Chemogenetics
    Stuart Schreiber; Fiscal Year: 2007
    ....
  3. STUDIES OF MATERIALS WITH PHYSIOLOGICAL PROPERTIES
    Stuart Schreiber; Fiscal Year: 2005
    ..These small molecules serve as probes of the processes they modify and illuminate the ways in which small molecules might convert diseased states into healthy states. ..
  4. STUDIES OF MATERIALS WITH PHYSIOLOGICAL PROPERTIES
    Stuart Schreiber; Fiscal Year: 2004
    ..These small molecules serve as probes of the processes they modify and illuminate the ways in which small molecules might convert diseased states into healthy states. ..
  5. STUDIES OF MATERIALS WITH PHYSIOLOGICAL PROPERTIES
    Stuart Schreiber; Fiscal Year: 2002
    ..These small molecules serve as probes of the processes they modify and illuminate the ways in which small molecules might convert diseased states into healthy states. ..
  6. CONTROLLING SIGNAL TRANSDUCTION WITH SYNTHETIC LIGANDS
    Stuart Schreiber; Fiscal Year: 2001
    ....
  7. SYNTHESIS OF MATERIALS WITH PHYSIOLOGICAL PROPERTIES
    Stuart Schreiber; Fiscal Year: 1990
    ..The two directional chain synthesis strategy promises to be efficient and highly enantioselective...
  8. CONTROLLING SIGNAL TRANSDUCTION WITH SYNTHETIC LIGANDS
    Stuart Schreiber; Fiscal Year: 1999
    ....
  9. STUDIES OF MATERIALS WITH PHYSIOLOGICAL PROPERTIES
    Stuart Schreiber; Fiscal Year: 2005
    ..These small molecules serve as probes of the processes they modify and illuminate the ways in which small molecules might convert diseased states into healthy states. ..
  10. STUDIES OF MATERIALS WITH PHYSIOLOGICAL PROPERTIES
    Stuart Schreiber; Fiscal Year: 2003
    ..These small molecules serve as probes of the processes they modify and illuminate the ways in which small molecules might convert diseased states into healthy states. ..
  11. CONTROLLING SIGNAL TRANSDUCTION WITH SYNTHETIC LIGANDS
    Stuart Schreiber; Fiscal Year: 2000
    ....
  12. SYNTHESIS OF MATERIALS WITH PHYSIOLOGICAL PROPERTIES
    Stuart Schreiber; Fiscal Year: 1991
    ..The two directional chain synthesis strategy promises to be efficient and highly enantioselective...
  13. STUDIES OF MATERIALS WITH PHYSIOLOGICAL PROPERTIES
    Stuart Schreiber; Fiscal Year: 2009
    ..The proposed continuation research aims to discover new small molecules that target new elements of these pathways and to perform experiments that will illuminate their most promising medical applications. ..
  14. An Integrated Approach to Diversity-Oriented Synthesis
    Stuart Schreiber; Fiscal Year: 2007
    ..abstract_text> ..
  15. STUDIES OF MATERIALS WITH PHYSIOLOGICAL PROPERTIES
    Stuart Schreiber; Fiscal Year: 2007
    ..The proposed continuation research aims to discover new small molecules that target new elements of these pathways and to perform experiments that will illuminate their most promising medical applications. ..
  16. STUDIES OF MATERIALS WITH PHYSIOLOGICAL PROPERTIES
    Stuart Schreiber; Fiscal Year: 2006
    ..The proposed continuation research aims to discover new small molecules that target new elements of these pathways and to perform experiments that will illuminate their most promising medical applications. ..
  17. STUDIES OF MATERIALS WITH PHYSIOLOGICAL PROPERTIES
    Stuart Schreiber; Fiscal Year: 2003
    ..These small molecules serve as probes of the processes they modify and illuminate the ways in which small molecules might convert diseased states into healthy states. ..
  18. CONTROLLING SIGNAL TRANSDUCTION WITH SYNTHETIC LIGANDS
    Stuart Schreiber; Fiscal Year: 2002
    ....