Now showing items 1-12 of 12

    • Chemical genetic strategy identifies histone deacetylase 1 (HDAC1) and HDAC2 as therapeutic targets in sickle cell disease 

      Bradner, James Elliott; Mak, Raymond Heungwing; Tanguturi, Shyam Kumar; Mazitschek, Ralph; Haggarty, Stephen John; Ross, Kenneth N; Chang, Cindy Y.; Bosco, Jocelyn; West, Nathan; Morse, Elizabeth; Lin, Katherine; Shen, John Paul; Kwiatkowski, Nicholas Paul; Gheldof, Nele; Dekker, Job; DeAngelo, Daniel J.; Carr, Steven A.; Schreiber, Stuart L.; Golub, Todd Robert; Ebert, Benjamin L. (Proceedings of the National Academy of Sciences, 2010)
      The worldwide burden of sickle cell disease is enormous, with over 200,000 infants born with the disease each year in Africa alone. Induction of fetal hemoglobin is a validated strategy to improve symptoms and complications ...
    • Chemical Neurobiology of the Histone Lysine Demethylase KDM1A 

      Ricq, Emily (2016-05-18)
      Epigenetic mechanisms regulate gene expression and mediate interactions between genetic factors and environmental exposures. The enzymes responsible for epigenetic regulation may thus be important therapeutic targets for ...
    • A genomic and evolutionary approach reveals non-genetic drug resistance in malaria 

      Herman, Jonathan D; Rice, Daniel P; Ribacke, Ulf; Silterra, Jacob; Deik, Amy A; Moss, Eli L; Broadbent, Kate M; Neafsey, Daniel E; Desai, Michael M; Clish, Clary B; Mazitschek, Ralph; Wirth, Dyann F (BioMed Central, 2014)
      Background: Drug resistance remains a major public health challenge for malaria treatment and eradication. Individual loci associated with drug resistance to many antimalarials have been identified, but their epistasis ...
    • HDAC2 Negatively Regulates Memory Formation and Synaptic Plasticity 

      Guan, Ji-Song; Giacometti, Emanuela; Dannenberg, Jan-Hermen; Joseph, Nadine; Gao, Jun; DePinho, Ronald A.; Jaenisch, Rudolf; Tsai, Li-Huei; Haggarty, Stephen John; Nieland, Thomas; Zhou, Ying; Wang, Xinyu; Mazitschek, Ralph; Bradner, James Elliott (Nature Publishing Group, 2012)
      Chromatin modifications, especially histone-tail acetylation, have been implicated in memory formation. Increased histone-tail acetylation induced by inhibitors of histone deacetylases (HDACis) facilitates learning and ...
    • 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). ...
    • 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 Small Molecules that Enhance Synaptogenesis Using Synapse Microarrays 

      Shi, Peng; Scott, Mark A; Ghosh, Balaram; Wan, Dongpeng; Wissner-Gross, Zachary; Mazitschek, Ralph; Haggarty, Stephen John; Yanik, Mehmet Fatih (Nature Publishing Group, 2011)
      Synaptic function is affected in many brain diseases and disorders. Technologies for large-scale synapse assays can facilitate identification of drug leads. Here we report a “synapse microarray” technology that enables ...
    • Light Controlled Modulation of Gene Expression by Chemical Optoepigenetic Probes 

      Reis, Surya A.; Ghosh, Balaram; Hendricks, J. Adam; Szantai-Kis, D. Miklos; Törk, Lisa; Ross, Kenneth N.; Lamb, Justin; Read-Button, Willis; Zheng, Baixue; Wang, Hongtao; Salthouse, Christopher; Haggarty, Stephen J.; Mazitschek, Ralph (2016)
      Epigenetic gene regulation is a dynamic process orchestrated by chromatin-modifying enzymes. Many of these master regulators exert their function through covalent modification of DNA and histone proteins. Aberrant epigenetic ...
    • Live-cell multiphoton fluorescence correlation spectroscopy with an improved large Stokes shift fluorescent protein 

      Guan, Yinghua; Meurer, Matthias; Raghavan, Sarada; Rebane, Aleksander; Lindquist, Jake R.; Santos, Sofia; Kats, Ilia; Davidson, Michael W.; Mazitschek, Ralph; Hughes, Thomas E.; Drobizhev, Mikhail; Knop, Michael; Shah, Jagesh V. (The American Society for Cell Biology, 2015)
      We report an improved variant of mKeima, a monomeric long Stokes shift red fluorescent protein, hmKeima8.5. The increased intracellular brightness and large Stokes shift (∼180 nm) make it an excellent partner with teal ...
    • Monoalkoxy BODIPYs—A Fluorophore Class for Bioimaging 

      Courtis, Alexandra M.; Santos, Sofia A.; Guan, Yinghua; Hendricks, J. Adam; Ghosh, Balaram; Szantai-Kis, D. Miklos; Reis, Surya A.; Shah, Jagesh V.; Mazitschek, Ralph (American Chemical Society, 2014)
      Small molecule fluorophores are indispensable tools for modern biomedical imaging techniques. In this report, we present the development of a new class of BODIPY dyes based on an alkoxy-fluoro-boron-dipyrromethene core. ...
    • Septins promote dendrite and axon development by negatively regulating microtubule stability via HDAC6-mediated deacetylation 

      Ageta-Ishihara, Natsumi; Miyata, Takaki; Ohshima, Chika; Watanabe, Masahiko; Sato, Yoshikatsu; Hamamura, Yuki; Higashiyama, Tetsuya; Mazitschek, Ralph; Bito, Haruhiko; Kinoshita, Makoto (Nature Pub. Group, 2013)
      Neurite growth requires two guanine nucleotide-binding protein polymers of tubulins and septins. However, whether and how those cytoskeletal systems are coordinated was unknown. Here we show that the acute knockdown or ...
    • Targeting class I histone deacetylase 2 in MYC amplified group 3 medulloblastoma 

      Ecker, Jonas; Oehme, Ina; Mazitschek, Ralph; Korshunov, Andrey; Kool, Marcel; Hielscher, Thomas; Kiss, Judit; Selt, Florian; Konrad, Carina; Lodrini, Marco; Deubzer, Hedwig E; von Deimling, Andreas; Kulozik, Andreas E; Pfister, Stefan M; Witt, Olaf; Milde, Till (BioMed Central, 2015)
      Introduction: Medulloblastoma (MB) is the most frequent malignant brain tumor in children. Four subgroups with distinct genetic, epigenetic and clinical characteristics have been identified. Survival remains particularly ...