KAREN L O'MALLEY

Summary

Affiliation: Washington University School of Medicine
Country: USA

Publications

  1. ncbi request reprint Activation of metabotropic glutamate receptor mGlu5 on nuclear membranes mediates intranuclear Ca2+ changes in heterologous cell types and neurons
    KAREN L O'MALLEY
    Department of Anatomy, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 278:28210-9. 2003
  2. ncbi request reprint Targeted expression of BCL-2 attenuates MPP+ but not 6-OHDA induced cell death in dopaminergic neurons
    KAREN L O'MALLEY
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO 63108, USA
    Neurobiol Dis 14:43-51. 2003
  3. pmc 6-OHDA generated ROS induces DNA damage and p53- and PUMA-dependent cell death
    Alison I Bernstein
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St, Louis, MO 63110, USA
    Mol Neurodegener 6:2. 2011
  4. ncbi request reprint Functional metabotropic glutamate receptors on nuclei from brain and primary cultured striatal neurons. Role of transporters in delivering ligand
    Yuh Jiin I Jong
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 280:30469-80. 2005
  5. ncbi request reprint Oxidative stress-triggered unfolded protein response is upstream of intrinsic cell death evoked by parkinsonian mimetics
    William A Holtz
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurochem 99:54-69. 2006
  6. pmc Activation of intracellular metabotropic glutamate receptor 5 in striatal neurons leads to up-regulation of genes associated with sustained synaptic transmission including Arc/Arg3.1 protein
    Vikas Kumar
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 287:5412-25. 2012
  7. pmc Intracellular metabotropic glutamate receptor 5 (mGluR5) activates signaling cascades distinct from cell surface counterparts
    Yuh Jiin I Jong
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 284:35827-38. 2009
  8. pmc Intracellular mGluR5 can mediate synaptic plasticity in the hippocampus
    Carolyn A Purgert
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, and Department of Psychiatry and Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St Louis, Missouri 63110
    J Neurosci 34:4589-98. 2014
  9. pmc Sequences located within the N-terminus of the PD-linked LRRK2 lead to increased aggregation and attenuation of 6-hydroxydopamine-induced cell death
    Neeraj Pandey
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri, USA
    PLoS ONE 7:e45149. 2012
  10. ncbi request reprint Rat tyrosine hydroxylase promoter directs tetracycline-inducible foreign gene expression in dopaminergic cell types
    Mossa Gardaneh
    Department of Anatomy and Neurobiology, Washington University School of Medicine, Campus Box 8108, 660 S Euclid Ave, St Louis, MO 63110, USA
    Brain Res Mol Brain Res 126:173-80. 2004

Research Grants

Collaborators

Detail Information

Publications27

  1. ncbi request reprint Activation of metabotropic glutamate receptor mGlu5 on nuclear membranes mediates intranuclear Ca2+ changes in heterologous cell types and neurons
    KAREN L O'MALLEY
    Department of Anatomy, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 278:28210-9. 2003
    ..Similarly, activation of mGlu5 receptors expressed on neuronal nuclei led to sustained Ca2+ oscillatory responses. These results suggest mGlu5 may mediate intranuclear signaling pathways...
  2. ncbi request reprint Targeted expression of BCL-2 attenuates MPP+ but not 6-OHDA induced cell death in dopaminergic neurons
    KAREN L O'MALLEY
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO 63108, USA
    Neurobiol Dis 14:43-51. 2003
    ..Thus, differential cell death pathways are associated with these cytotoxic signals in primary models of Parkinson's disease...
  3. pmc 6-OHDA generated ROS induces DNA damage and p53- and PUMA-dependent cell death
    Alison I Bernstein
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St, Louis, MO 63110, USA
    Mol Neurodegener 6:2. 2011
    ..abstract:..
  4. ncbi request reprint Functional metabotropic glutamate receptors on nuclei from brain and primary cultured striatal neurons. Role of transporters in delivering ligand
    Yuh Jiin I Jong
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 280:30469-80. 2005
    ..These studies demonstrated that mGlu5 receptors play a dynamic role in signaling both on and off the plasma membrane...
  5. ncbi request reprint Oxidative stress-triggered unfolded protein response is upstream of intrinsic cell death evoked by parkinsonian mimetics
    William A Holtz
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurochem 99:54-69. 2006
    ..Taken together, 6-OHDA-mediated cell death in dopaminergic cells proceeds via ROS-dependent UPR up-regulation which leads to an interaction with the intrinsic mitochondrial pathway and downstream caspase activation...
  6. pmc Activation of intracellular metabotropic glutamate receptor 5 in striatal neurons leads to up-regulation of genes associated with sustained synaptic transmission including Arc/Arg3.1 protein
    Vikas Kumar
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 287:5412-25. 2012
    ..Taken together, these data highlight the importance of intracellular mGluR5 in the cascade of events associated with sustained synaptic transmission...
  7. pmc Intracellular metabotropic glutamate receptor 5 (mGluR5) activates signaling cascades distinct from cell surface counterparts
    Yuh Jiin I Jong
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 284:35827-38. 2009
    ..Glutamate activation of intracellular mGluR5 serves an important role in the regulation of nuclear Ca(2+), transcriptional activation, and gene expression necessary for physiological processes such as synaptic plasticity...
  8. pmc Intracellular mGluR5 can mediate synaptic plasticity in the hippocampus
    Carolyn A Purgert
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, and Department of Psychiatry and Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St Louis, Missouri 63110
    J Neurosci 34:4589-98. 2014
    ..These data suggest a physiologically relevant and important role for intracellular mGluR5 in hippocampal synaptic plasticity. ..
  9. pmc Sequences located within the N-terminus of the PD-linked LRRK2 lead to increased aggregation and attenuation of 6-hydroxydopamine-induced cell death
    Neeraj Pandey
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri, USA
    PLoS ONE 7:e45149. 2012
    ..Finally, in support of the hypothesis that aggregates represent a self-protection strategy, aggregated N-terminal LRRK2 constructs significantly attenuated cell death induced by the PD-mimetic, 6-hydroxydopamine (6-OHDA)...
  10. ncbi request reprint Rat tyrosine hydroxylase promoter directs tetracycline-inducible foreign gene expression in dopaminergic cell types
    Mossa Gardaneh
    Department of Anatomy and Neurobiology, Washington University School of Medicine, Campus Box 8108, 660 S Euclid Ave, St Louis, MO 63110, USA
    Brain Res Mol Brain Res 126:173-80. 2004
    ..Taken together, these data suggest that targeted, inducible gene expression can be achieved in dopaminergic cell types...
  11. ncbi request reprint Wld(S) mice are protected against the Parkinsonian mimetic MPTP
    Daphne M Hasbani
    Department of Anatomy and Neurobiology, Washington University School of Medicine, Campus Box 8108, 660 S Euclid Ave, St Louis, MO 63110, USA
    Exp Neurol 202:93-9. 2006
    ..These results suggest new therapeutic avenues for Parkinson's disease...
  12. pmc Activated nuclear metabotropic glutamate receptor mGlu5 couples to nuclear Gq/11 proteins to generate inositol 1,4,5-trisphosphate-mediated nuclear Ca2+ release
    Vikas Kumar
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 283:14072-83. 2008
    ..Thus the nucleus can function as an autonomous organelle independent of signals originating in the cytoplasm, and nuclear mGlu5 receptors play a dynamic role in mobilizing Ca2+ in a specific, localized fashion...
  13. ncbi request reprint Nuclear localization of functional metabotropic glutamate receptor mGlu1 in HEK293 cells and cortical neurons: role in nuclear calcium mobilization and development
    Yuh Jiin I Jong
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurochem 101:458-69. 2007
    ....
  14. pmc The parkinsonian mimetic, MPP+, specifically impairs mitochondrial transport in dopamine axons
    Jeong Sook Kim-Han
    Department of Anatomy and Neurobiology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA
    J Neurosci 31:7212-21. 2011
    ..Since these drugs also rescued processes from degeneration, these findings emphasize the need to develop therapeutics aimed at axons as well as cell bodies to preserve "normal" circuitry and function as long as possible...
  15. pmc MPP+-induces PUMA- and p53-dependent, but ATF3-independent cell death
    Alison I Bernstein
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Toxicol Lett 219:93-8. 2013
    ..These studies revealed that PUMA and p53, but not ATF3, are required for MPP(+)-induced cell death, suggesting that UPR activation is parallel to the induction of MPP(+)-induced cell death...
  16. pmc WldS but not Nmnat1 protects dopaminergic neurites from MPP+ neurotoxicity
    Jo Ann V Antenor-Dorsey
    Department of Anatomy and Neurobiology, Washington University School of Medicine, Saint Louis, MO 63110, USA
    Mol Neurodegener 7:5. 2012
    ..Here, we used dissociated dopaminergic cultures to test the hypothesis that catalytically active Nmnat1 protects dopaminergic neurons from toxin-mediated axonal injury...
  17. ncbi request reprint Cell stress induced by the parkinsonian mimetic, 6-hydroxydopamine, is concurrent with oxidation of the chaperone, ERp57, and aggresome formation
    Jeong Sook Kim-Han
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Antioxid Redox Signal 9:2255-64. 2007
    ..Understanding the signaling mechanisms associated with parkinsonian mimetics, as well as their temporal induction, may aid in designing better interventions in models of PD...
  18. pmc The Parkinsonian mimetic, 6-OHDA, impairs axonal transport in dopaminergic axons
    Xi Lu
    Department of Biomedical Engineering, Washington University in Saint Louis, 1 Brookings Drive, Campus Box 1097, St, Louis, MO 63130, USA
    Mol Neurodegener 9:17. 2014
    ..The results from the study suggest that ROS-mediated transport dysfunction occurs early and plays a significant role in inducing axonal degeneration in response to 6-OHDA treatment. ..
  19. ncbi request reprint Alpha-synuclein protects naive but not dbcAMP-treated dopaminergic cell types from 1-methyl-4-phenylpyridinium toxicity
    Penny J Jensen
    Washington University School of Medicine, Anatomy and Neurobiology Department, St Louis, Missouri 63110, USA
    J Neurochem 86:196-209. 2003
    ..These results suggest that the normal physiological role for alpha-synuclein may change during development...
  20. ncbi request reprint Dopamine depletion does not protect against acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in vivo
    Daphne M Hasbani
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 25:9428-33. 2005
    ..These results suggest that DA does not contribute to acute MPTP toxicity in vivo...
  21. pmc Location-dependent signaling of the group 1 metabotropic glutamate receptor mGlu5
    Yuh Jiin I Jong
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri
    Mol Pharmacol 86:774-85. 2014
    ..Further elucidation of the site(s) of action of these drugs may determine which signal pathways mediate therapeutic efficacy. ..
  22. pmc A microdevice platform for visualizing mitochondrial transport in aligned dopaminergic axons
    Xi Lu
    Department of Biomedical Engineering, Washington University, St Louis, MO 63130, USA
    J Neurosci Methods 209:35-9. 2012
    ..The methodology and device that we have described here will allow further study of the role of mitochondrial transport defects play in major neurodegenerative diseases...
  23. pmc Reduced striatal dopamine underlies the attention system dysfunction in neurofibromatosis-1 mutant mice
    Jacquelyn A Brown
    Department of Neurology, Washington University School of Medicine, St Louis, MO, USA
    Hum Mol Genet 19:4515-28. 2010
    ..Collectively, these data establish abnormal DA homeostasis as the primary biochemical defect underlying the attention system dysfunction in Nf1 GEM relevant to children with NF1...
  24. ncbi request reprint Microarray expression profiling identifies early signaling transcripts associated with 6-OHDA-induced dopaminergic cell death
    William A Holtz
    Washington University School of Medicine, Anatomy and Neurobiology Department, St Louis, MO 63110, USA
    Antioxid Redox Signal 7:639-48. 2005
    ..Taken together, these data support the notion that oxidative stress and protein dysfunction play a role in Parkinson's disease, as well as provide a time course for many of the molecular events associated with 6-OHDA neurotoxicity...
  25. pmc Comprehensive functional characterization of murine infantile Batten disease including Parkinson-like behavior and dopaminergic markers
    Joshua T Dearborn
    Department of Internal Medicine, Washington University in St Louis School of Medicine, St Louis, MO, USA
    Sci Rep 5:12752. 2015
    ..Results from this study demonstrate quantifiable changes in behavioral functions during progression of murine INCL and suggest that Parkinson-like motor/sensorimotor deficits in Cln1(-/-) mice are not mediated by dopamine deficiency. ..
  26. pmc Functional G protein-coupled receptors on nuclei from brain and primary cultured neurons
    Yuh Jiin I Jong
    Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid Ave, Saint Louis, MO, 63110, USA
    Methods Mol Biol 1234:113-21. 2015
    ..Here we describe how to isolate nuclei that are free from plasma membrane and cytoplasmic contamination yet still exhibit physiological properties following receptor activation. ..
  27. pmc Reassessment of the role of aromatic amino acid hydroxylases and the effect of infection by Toxoplasma gondii on host dopamine
    Zi T Wang
    Department of Molecular Microbiology, School of Medicine, Washington University in St Louis, St Louis, Missouri, USA
    Infect Immun 83:1039-47. 2015
    ..Additionally, our findings suggest alternative roles for the AHH enzymes in T. gondii, since AAH1 is essential for growth in nondopaminergic cells. ..

Research Grants6

  1. MODULATION OF DOPAMINE AUTORECEPTOR FUNCTION BY COCAINE
    KAREN O MALLEY; Fiscal Year: 2001
    ..Taken together these studies will significantly extend our ongoing efforts to understand the complex receptor/presynaptic effector interactions involved in the reinforcing and behavioral sensitization effects of cocaine. ..
  2. Signaling By Nuclear G-Protein Coupled Receptors
    KAREN O MALLEY; Fiscal Year: 2005
    ..Direct nuclear calcium regulation represents a novel signaling strategy by which intracellular receptors such as mGlu5 may play a pivotal role in generating and shaping intracellular Ca2+ signals ..
  3. Metabotropic Receptors: Structure/Function/Regulation
    KAREN O MALLEY; Fiscal Year: 2006
    ..We anticipate that these investigations of mGluR dimerization will deepen our understanding of neural communication and signal transduction, processes that underlie brain function and dysfunction. ..
  4. TRANSCRIPTIONAL CONTROL OF NEUROENDOCRINE GENES
    KAREN O MALLEY; Fiscal Year: 2007
    ..Knowledge gained from these studies may offer new routes for therapeutic intervention. ..
  5. Functional Consequences of Nuclear mGlu5 Receptor Activation
    KAREN O MALLEY; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  6. MECHANISMS OF NEURONAL DEATH IN PARKINSON'S DISEASE
    KAREN O MALLEY; Fiscal Year: 2008
    ..If so, novel therapies can be targeted to the elucidated control points in order to stop or slow disease progression. ..