Browsing by Author "Schreiber, Stuart"

Now showing items 21-40 of 62

    • Expanding Stereochemical and Skeletal Diversity Using Petasis Reactions and 1,3-Dipolar Cycloadditions 

      Muncipinto, Giovanni; Kaya, Taner; Wilson, J. Anthony; Kumagai, Naoya; Clemons, Paul A.; Schreiber, Stuart L. (American Chemical Society, 2010)
      A short and modular synthetic pathway using intramolecular 1,3-dipolar cycloaddition reactions and yielding functionalized isoxazoles, isoxazolines, and isoxazolidines is described. The change in shape of previous compounds ...

    • A genetic basis for the variation in the vulnerability of cancer to DNA damage 

      Yard, Brian D.; Adams, Drew J.; Chie, Eui Kyu; Tamayo, Pablo; Battaglia, Jessica S.; Gopal, Priyanka; Rogacki, Kevin; Pearson, Bradley E.; Phillips, James; Raymond, Daniel P.; Pennell, Nathan A.; Almeida, Francisco; Cheah, Jaime H.; Clemons, Paul A.; Shamji, Alykhan; Peacock, Craig D.; Schreiber, Stuart L.; Hammerman, Peter S.; Abazeed, Mohamed E. (Nature Publishing Group, 2016)
      Radiotherapy is not currently informed by the genetic composition of an individual patient's tumour. To identify genetic features regulating survival after DNA damage, here we conduct large-scale profiling of cellular ...

    • Global Nucleosome Occupancy in Yeast 

      Bernstein, Bradley E.; Liu, Chih Long; Humphrey, Emily L; Perlstein, Ethan O; Schreiber, Stuart L. (BioMed Central, 2004)
      A genome-wide study of nucleosome occupancy at yeast promoters shows that promoters that regulate active genes, contain multiple conserved motifs, or contain Rap1 binding sites tend to be depleted of nucleosomes.

    • Gold(I)-Catalyzed Coupling Reactions for the Synthesis of Diverse Small Molecules Using the Build/Couple/Pair Strategy 

      Luo, Tuoping; Schreiber, Stuart L. (American Chemical Society, 2009)
      The build/couple/pair strategy has yielded small molecules with stereochemical and skeletal diversity by using short reaction sequences. Subsequent screening has shown that these compounds can achieve biological tasks ...

    • GW8510 Increases Insulin Expression in Pancreatic Alpha Cells through Activation of p53 Transcriptional Activity 

      Fomina-Yadlin, Dina; Kubicek, Stefan; Vetere, Amedeo; He, Kaihui Hu; Schreiber, Stuart L.; Wagner, Bridget K. (Public Library of Science, 2012)
      Background: Expression of insulin in terminally differentiated non-beta cell types in the pancreas could be important to treating type-1 diabetes. Previous findings led us to hypothesize involvement of kinase inhibition ...

    • HDAC6 Inhibitors Modulate Lys49 Acetylation and Membrane Localization of β-Catenin in Human iPSC-Derived Neuronal Cells 

      Iaconelli, Jonathan; Huang, Joanne H.; Berkovitch, Shaunna S.; Chattopadhyay, Shrikanta; Mazitschek, Ralph; Schreiber, Stuart L.; Haggarty, Stephen J.; Karmacharya, Rakesh (American Chemical Society, 2014)
      We examined the effects of isoform-specific histone deacetylase (HDAC) inhibitors on β-catenin posttranslational modifications in neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs). ...

    • High-Throughput Screen in Cryptococcus neoformans Identifies a Novel Molecular Scaffold That Inhibits Cell Wall Integrity Pathway Signaling 

      Hartland, Kate; Pu, Jun; Palmer, Michelle; Dandapani, Sivaraman; Moquist, Philip N.; Munoz, Benito; DiDone, Louis; Schreiber, Stuart L.; Krysan, Damian J. (American Chemical Society, 2015)
      Cryptococcus neoformans is one of the most important human fungal pathogens; however, no new therapies have been developed in over 50 years. Fungicidal activity is crucially important for an effective anticryptococal agent ...

    • Identification and Characterization of Small Molecule Inhibitors of a Class I Histone Deacetylase from Plasmodium falciparum 

      Nguyen, Cokey; Urgaonkar, Sameer; Cortese, Joseph; Barker, Robert H.; Greenberg, Edward; Tang, Weiping; Patel, Vishal; Mazitschek, Ralph; Coleman, Bradley Ian; Bradner, James Elliott; Schreiber, Stuart L.; Duraisingh, Manoj T.; Wirth, Dyann Fergus; Clardy, Jon C. (American Chemical Society, 2009)
      A library of approximately 2000 small molecules biased toward inhibition of histone deacetylases was assayed for antimalarial activity in a high-throughput P. falciparum viability assay. Active compounds were cross-analyzed ...

    • Identification of a Selective Small Molecule Inhibitor of Breast Cancer Stem Cells 

      Germain, Andrew R.; Carmody, Leigh C.; Morgan, Barbara; Fernandez, Cristina; Forbeck, Erin; Lewis, Timothy A.; Nag, Partha P.; Ting, Amal; VerPlank, Lynn; Feng, Yuxiong; Perez, Jose R.; Dandapani, Sivaraman; Palmer, Michelle; Lander, Eric Steven; Gupta, Piyush B.; Schreiber, Stuart L.; Munoz, Benito (Elsevier BV, 2012)
      A high-throughput screen (HTS) with the National Institute of Health–Molecular Libraries Small Molecule Repository (NIH–MLSMR) compound collection identified a class of acyl hydrazones to be selectively lethal to breast ...

    • Identification of cancer cytotoxic modulators of PDE3A by predictive chemogenomics 

      de Waal, Luc; Lewis, Timothy A.; Rees, Matthew G.; Tsherniak, Aviad; Wu, Xiaoyun; Choi, Peter S.; Gechijian, Lara; Hartigan, Christina; Faloon, Patrick W.; Hickey, Mark J.; Tolliday, Nicola; Carr, Steven A.; Clemons, Paul A.; Munoz, Benito; Wagner, Bridget K.; Shamji, Alykhan F.; Koehler, Angela N.; Schenone, Monica; Burgin, Alex B.; Schreiber, Stuart L.; Greulich, Heidi; Meyerson, Matthew (2015)
      High cancer death rates indicate the need for new anti-cancer therapeutic agents. Approaches to discover new cancer drugs include target-based drug discovery and phenotypic screening. Here, we identified phosphodiesterase ...

    • Integrated genetic and pharmacologic interrogation of rare cancers 

      Hong, Andrew L.; Tseng, Yuen-Yi; Cowley, Glenn S.; Jonas, Oliver; Cheah, Jaime H.; Kynnap, Bryan D.; Doshi, Mihir B.; Oh, Coyin; Meyer, Stephanie C.; Church, Alanna J.; Gill, Shubhroz; Bielski, Craig M.; Keskula, Paula; Imamovic, Alma; Howell, Sara; Kryukov, Gregory V.; Clemons, Paul A.; Tsherniak, Aviad; Vazquez, Francisca; Crompton, Brian D.; Shamji, Alykhan F.; Rodriguez-Galindo, Carlos; Janeway, Katherine A.; Roberts, Charles W. M.; Stegmaier, Kimberly; van Hummelen, Paul; Cima, Michael J.; Langer, Robert S.; Garraway, Levi A.; Schreiber, Stuart L.; Root, David E.; Hahn, William C.; Boehm, Jesse S. (Nature Publishing Group, 2016)
      Identifying therapeutic targets in rare cancers remains challenging due to the paucity of established models to perform preclinical studies. As a proof-of-concept, we developed a patient-derived cancer cell line, CLF-PED-015-T, ...

    • An Interactive Resource to Identify Cancer Genetic and Lineage Dependencies Targeted by Small Molecules 

      Basu, Amrita; Bodycombe, Nicole E.; Cheah, Jaime H.; Price, Edmund V.; Liu, Ke; Schaefer, Giannina Ines; Ebright, Richard Yon; Stewart, Michelle L.; Ito, Daisuke; Wang, Stephanie; Bracha, Abigail L.; Liefeld, Ted; Wawer, Mathias; Gilbert, Joshua C.; Wilson, Andrew J.; Stransky, Nicolas; Kryukov, Gregory V.; Dancik, Vlado; Barretina, Jordi; Garraway, Levi Alexander; Hon, C. Suk-Yee; Munoz, Benito; Bittker, Joshua A.; Stockwell, Brent R.; Khabele, Dineo; Stern, Andrew M.; Clemons, Paul A.; Shamji, Alykhan F.; Schreiber, Stuart L. (Elsevier BV, 2013)
      The high rate of clinical response to protein-kinase-targeting drugs matched to cancer patients with specific genomic alterations has prompted efforts to use cancer cell line (CCL) profiling to identify additional biomarkers ...

    • The kinase DYRK1A reciprocally regulates the differentiation of Th17 and regulatory T cells 

      Khor, Bernard; Gagnon, John D; Goel, Gautam; Roche, Marly I; Conway, Kara L; Tran, Khoa; Aldrich, Leslie N; Sundberg, Thomas B; Paterson, Alison M; Mordecai, Scott; Dombkowski, David; Schirmer, Melanie; Tan, Pauline H; Bhan, Atul K; Roychoudhuri, Rahul; Restifo, Nicholas P; O'Shea, John J; Medoff, Benjamin D; Shamji, Alykhan F; Schreiber, Stuart L; Sharpe, Arlene H; Shaw, Stanley Y; Xavier, Ramnik J (eLife Sciences Publications, Ltd, 2015)
      The balance between Th17 and T regulatory (Treg) cells critically modulates immune homeostasis, with an inadequate Treg response contributing to inflammatory disease. Using an unbiased chemical biology approach, we identified ...

    • The Landscape of Cancer Cell Line Metabolism 

      Li, Haoxin; Ning, Shaoyang; Gopal, Shuba; Deik, Amy; Souza, Amanda; Pierce, Kerry; Keskula, Paula; Hernandez, Desiree; Ann, Julie; Shkoza, Dojna; Apfel, Verena; Zou, Yilong; Vazquez, Francisca; Barretina, Jordi; Tsherniak, Aviad; Giannakis, Marios; Ghandi, Mahmoud; Kryukov, Gregory; Pagliarini, Raymond; Galli, Giorgio; Root, David; Hahn, William; Schreiber, Stuart; Clish, Clary; Garraway, Levi; Sellers, William (Springer Science and Business Media LLC, 2019-05)
      Despite considerable efforts to identify cancer metabolic alterations that might unveil druggable vulnerabilities, systematic characterizations of metabolism as it relates to functional genomic features and associated ...

    • Late-Stage Fluorination With 19F− and 18F− via Concerted Nucleophilic Aromatic Substitution 

      Neumann, Constanze N. (2016-09-09)
      The formation of C–F bonds has long been considered a challenging transformation and C–F bonds commonly had to be formed early on in a synthetic sequence towards complex organofluorides. Late-stage fluorination reactions ...

    • Methylation of histone H3 Lys 4 in coding regions of active genes 

      Bernstein, Bradley E.; Humphrey, E. L.; Erlich, R; Schneider, R.; Bouman, P.; Liu, Jun; Kouzarides, T.; Schreiber, Stuart L. (Proceedings of the National Academy of Sciences, 2002)
      Posttranslational modifications of histone tails regulate chromatin structure and transcription. Here we present global analyses of histone acetylation and histone H3 Lys 4 methylation patterns in yeast. We observe a ...

    • Modulators of Cellular and Biochemical PRC2 Activity 

      Paulk, Joshiawa Lanair James (2014-10-21)
      EZH2 is a SET domain-containing methyltransferase and the catalytic component of the multimeric Polycomb- group (PcG) protein complex, PRC2. When in complex with other PRC2 members (EED, SUZ12, AEBP2, and RBBP4), EZH2 ...

    • Multilevel Regulation of Growth Rate in Yeast Revealed Using Systems Biology 

      Ramanathan, Arvind; Schreiber, Stuart L. (BioMed Central, 2007)
      The effect of changing growth rates on the transcriptome, proteome and metabolome has been systematically studied. Measurements made under varying nutrient conditions, corresponding to biochemical pathways that correlate ...

    • Multiplex Cytological Profiling Assay to Measure Diverse Cellular States 

      Gustafsdottir, Sigrun M.; Ljosa, Vebjorn; Sokolnicki, Katherine L.; Anthony Wilson, J.; Walpita, Deepika; Kemp, Melissa M.; Petri Seiler, Kathleen; Carrel, Hyman A.; Golub, Todd R.; Schreiber, Stuart L.; Clemons, Paul A.; Carpenter, Anne E.; Shamji, Alykhan F. (Public Library of Science, 2013)
      Computational methods for image-based profiling are under active development, but their success hinges on assays that can capture a wide range of phenotypes. We have developed a multiplex cytological profiling assay that ...

    • NAMPT Is the Cellular Target of STF-31-Like Small-Molecule Probes 

      Adams, Drew J.; Ito, Daisuke; Rees, Matthew G.; Seashore-Ludlow, Brinton; Puyang, Xiaoling; Ramos, Alex H.; Cheah, Jaime H.; Clemons, Paul A.; Warmuth, Markus; Zhu, Ping; Shamji, Alykhan F.; Schreiber, Stuart L. (American Chemical Society, 2014)
      The small-molecule probes STF-31 and its analogue compound 146 were discovered while searching for compounds that kill VHL-deficient renal cell carcinoma cell lines selectively and have been reported to act via direct ...