Browsing by Author "Haggarty, Stephen"

Now showing items 1-18 of 18

    • Automated Structure-Activity Relationship Mining: Connecting Chemical Structure to Biological Profiles 

      Wawer, M. J.; Jaramillo, D. E.; Dan ik, V.; Fass, D. M.; Haggarty, Stephen John; Shamji, A. F.; Wagner, B. K.; Schreiber, Stuart L.; Clemons, P. A. (SAGE Publications, 2014)
      Understanding the structure–activity relationships (SARs) of small molecules is important for developing probes and novel therapeutic agents in chemical biology and drug discovery. Increasingly, multiplexed small-molecule ...

    • Brain-Penetrant LSD1 Inhibitors Can Block Memory Consolidation 

      Neelamegam, Ramesh; Ricq, Emily Louise; Malvaez, Melissa; Patnaik, Debasis; Norton, Stephanie; Carlin, Stephen M.; Hill, Ian Thomas; Wood, Marcelo A.; Haggarty, Stephen John; Hooker, Jacob M (American Chemical Society (ACS), 2012)
      Modulation of histone modifications in the brain may represent a new mechanism for brain disorder therapy. Post-translational modifications of histones regulate gene expression, affecting major cellular processes such as ...

    • Characterization of Bipolar Disorder Patient-Specific Induced Pluripotent Stem Cells from a Family Reveals Neurodevelopmental and mRNA Expression Abnormalities 

      Madison, Jon M.; Zhou, Fen; Nigam, Aparna; Hussain, Ali; Barker, Douglas D.; Nehme, Ralda; van der Ven, Karlijn; Hsu, Jenny; Wolf, Pavlina; Fleishman, Morgan; O’Dushlaine, Colm; Rose, Sam; Chambert, Kimberly; Lau, Frank H.; Ahfeldt, Tim; Rueckert, Erroll H.; Sheridan, Steven D.; Fass, Daniel M.; Nemesh, James; Mullen, Thomas E.; Daheron, Laurence; McCarroll, Steve; Sklar, Pamela; Perlis, Roy H.; Haggarty, Stephen J. (2014)
      Bipolar disorder (BD) is a common neuropsychiatric disorder characterized by chronic recurrent episodes of depression and mania. Despite evidence for high heritability of BD, little is known about its underlying pathophysiology. ...

    • 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 ...

    • Class I HDAC imaging using [3H]CI-994 autoradiography 

      Wang, Yajie; Zhang, Yan-Ling; Hennig, Krista; Gale, Jennifer P.; Hong, Yijia; Cha, Anna; Riley, Misha; Wagner, Florence; Haggarty, Stephen John; Holson, Edward; Hooker, Jacob M (Landes Bioscience, 2013)
      [3H]CI-994, a radioactive isotopologue of the benzamide CI-994, a class I histone deacetylase inhibitor (HDACi), was evaluated as an autoradiography probe for ex vivo labeling and localizing of class I HDAC (isoforms 1–3) ...

    • Class I HDAC Inhibition Blocks Cocaine-Induced Plasticity Through Targeted Changes in Histone Methylation 

      Kennedy, Pamela J.; Feng, Jian; Robison, A.J.; Maze, Ian; Badimon, Ana; Mouzon, Ezekiell; Chaudhury, Dipesh; Damez-Werno, Diane M.; Haggarty, Stephen J.; Han, Ming-Hu; Bassel-Duby, Rhonda; Olson, Eric N.; Nestler, Eric J. (2013)
      Induction of histone acetylation in the nucleus accumbens (NAc), a key brain reward region, promotes cocaine-induced alterations in gene expression. Histone deacetylases (HDACs) tightly regulate the acetylation of histone ...

    • Design, Synthesis, and Evaluation of Hydroxamic Acid-Based Molecular Probes for In Vivo Imaging of Histone Deacetylase (HDAC) in Brain 

      Hooker, Jacob M; Wang, Changning; Eessalu, Thomas E.; Barth, Vanessa N.; Mitch, Charles H.; Wagner, Florence F.; Hong, Yijia; Neelamegam, Ramesh; Schroeder, Frederick A; Holson, Edward B.; Haggarty, Stephen John (e-Century Publishing, 2014)
      Hydroxamic acid-based histone deacetylase inhibitors (HDACis) are a class of molecules with therapeutic potential currently reflected in the use of suberoylanilide hydroxamic acid (SAHA; Vorinostat) to treat cutaneous ...

    • Dysregulation of miR-34a Links Neuronal Development to Genetic Risk Factors for Bipolar Disorder 

      Bavamian, Sabine; Mellios, Nikolaos; Lalonde, Jasmin; Fass, Daniel M.; Wang, Jennifer; Sheridan, Steven D.; Madison, Jon M.; Zhou, Fen; Rueckert, Erroll H.; Barker, Doug; Perlis, Roy H.; Sur, Mriganka; Haggarty, Stephen J. (2014)
      Bipolar disorder (BD) is a heritable neuropsychiatric disorder with largely unknown pathogenesis. Given their prominent role in brain function and disease, we hypothesized that microRNAs (miRNAs) might be of importance for ...

    • An Epigenetic Blockade of Cognitive Functions in the Neurodegenerating Brain 

      Gräff, Johannes; Rei, Damien; Guan, Ji-Song; Wang, Wen-Yuan; Seo, Jinsoo; Fass, Daniel M.; Kao, Patricia F.; Kahn, Martin; Su, Susan C.; Joseph, Nadine; Delalle, Ivana; Tsai, Li-Huei; Hennig, Krista M.; Nieland, Thomas; Samiei, Alireza; Haggarty, Stephen John (Nature Publishing Group, 2012)
      Cognitive decline is a debilitating feature of most neurodegenerative diseases of the central nervous system, including Alzheimer’s disease. The causes leading to such impairment are only poorly understood and effective ...

    • FDG-PET Imaging Reveals Local Brain Glucose Utilization Is Altered by Class I Histone Deacetylase Inhibitors 

      Schroeder, Frederick A; Chonde, Daniel Burje; Riley, Misha M.; Moseley, Christian K.; Granda, Michael L.; Wilson, Colin M.; Wagner, Florence F.; Zhang, Yan-Ling; Gale, Jennifer; Holson, Edward B.; Haggarty, Stephen John; Hooker, Jacob M (Elsevier BV, 2013)
      The purpose of this work – the first of its kind – was to evaluate the impact of chronic selective histone deacetylase (HDAC) inhibitor treatment on brain activity using uptake of the radioligand 18F-fluorodeoxyglucose and ...

    • 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 ...

    • A high-throughput kinome screen reveals serum/glucocorticoid-regulated kinase 1 as a therapeutic target for NF2-deficient meningiomas 

      Beauchamp, Roberta L.; James, Marianne; DeSouza, Patrick A.; Wagh, Vilas; Zhao, Wen-Ning; Jordan, Justin Thomas; Stemmer-Rachamimov, Anat; Plotkin, Scott Randall; Gusella, James Francis; Haggarty, Stephen John; Ramesh, Vijaya (Impact Journals, LLC, 2015)
      Meningiomas are the most common primary intracranial adult tumor. All Neurofibromatosis 2 (NF2)-associated meningiomas and ~60% of sporadic meningiomas show loss of NF2 tumor suppressor protein. There are no effective ...

    • 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 ...

    • In Vivo Imaging of Histone Deacetylases (HDACs) in the Central Nervous System and Major Peripheral Organs 

      Wang, Changning; Schroeder, Frederick A.; Wey, Hsiao-Ying; Borra, Ronald; Wagner, Florence F.; Reis, Surya; Kim, Sung Won; Holson, Edward B.; Haggarty, Stephen J.; Hooker, Jacob M. (American Chemical Society, 2014)
      Epigenetic enzymes are now targeted to treat the underlying gene expression dysregulation that contribute to disease pathogenesis. Histone deacetylases (HDACs) have shown broad potential in treatments against cancer and ...

    • 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 ...

    • A Selective HDAC 1/2 Inhibitor Modulates Chromatin and Gene Expression in Brain and Alters Mouse Behavior in Two Mood-Related Tests 

      Schroeder, Frederick A.; Lewis, Michael C.; Fass, Daniel M.; Wagner, Florence F.; Zhang, Yan-Ling; Hennig, Krista M.; Gale, Jennifer; Zhao, Wen-Ning; Reis, Surya; Barker, Douglas D.; Berry-Scott, Erin; Kim, Sung Won; Clore, Elizabeth L.; Hooker, Jacob M.; Holson, Edward B.; Haggarty, Stephen J.; Petryshen, Tracey L. (Public Library of Science, 2013)
      Psychiatric diseases, including schizophrenia, bipolar disorder and major depression, are projected to lead global disease burden within the next decade. Pharmacotherapy, the primary – albeit often ineffective – treatment ...

    • SpectralNET – an application for spectral graph analysis and visualization 

      Forman, Joshua J; Clemons, Paul A; Schreiber, Stuart L.; Haggarty, Stephen John (BioMed Central, 2005)
      Background: Graph theory provides a computational framework for modeling a variety of datasets including those emerging from genomics, proteomics, and chemical genetics. Networks of genes, proteins, small molecules, or ...