Jang Ho Cha

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. pmc Altered white matter microstructure in the corpus callosum in Huntington's disease: implications for cortical "disconnection"
    H Diana Rosas
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
    Neuroimage 49:2995-3004. 2010
  2. pmc Genome-wide significance for a modifier of age at neurological onset in Huntington's disease at 6q23-24: the HD MAPS study
    Jian Liang Li
    Department of Neurology, Boston University School of Medicine, Boston, MA, USA
    BMC Med Genet 7:71. 2006
  3. pmc Altered neurotransmitter receptor expression in transgenic mouse models of Huntington's disease
    J H Cha
    Department of Neurology, Massachusetts General Hospital, Boston 02114, USA
    Philos Trans R Soc Lond B Biol Sci 354:981-9. 1999
  4. pmc Transcriptional signatures in Huntington's disease
    Jang Ho J Cha
    MassGeneral Institute for Neurodegenerative Disease, 114 16th Street B114 2000, Charlestown, MA 02129 4404, USA
    Prog Neurobiol 83:228-48. 2007
  5. pmc Finding diamonds in the rubble
    Jang Ho J Cha
    Exp Neurol 205:1-4. 2007
  6. doi Environmental enrichment reduces neuronal intranuclear inclusion load but has no effect on messenger RNA expression in a mouse model of Huntington disease
    Caroline L Benn
    Mass General Institute for Neurodegenerative Disease, Charlestown, Massachusetts, USA
    J Neuropathol Exp Neurol 69:817-27. 2010
  7. ncbi Dopamine release is impaired in a mouse model of DYT1 dystonia
    Aygul Balcioglu
    MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
    J Neurochem 102:783-8. 2007
  8. ncbi Diffusion-weighted magnetic resonance imaging abnormalities in Bartonella encephalopathy
    Aneesh B Singhal
    Department of Neurology, Massachusetts General Hospital, Biogen, Inc MAP, Boston, USA
    J Neuroimaging 13:79-82. 2003
  9. doi Mechanisms of distribution of mouse beta-galactosidase in the adult GM1-gangliosidosis brain
    M L D Broekman
    Department of Neurology, Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Gene Ther 16:303-8. 2009
  10. ncbi Glutamate receptor dysregulation in the hippocampus of transgenic mice carrying mutated human amyloid precursor protein
    J H Cha
    Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
    Neurobiol Dis 8:90-102. 2001

Research Grants

Collaborators

Detail Information

Publications29

  1. pmc Altered white matter microstructure in the corpus callosum in Huntington's disease: implications for cortical "disconnection"
    H Diana Rosas
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
    Neuroimage 49:2995-3004. 2010
    ..Our findings provide evidence for early degeneration of commissural pyramidal neurons in the neocortex, loss of cortico-cortical connectivity, and functional compromise of associative cortical processing...
  2. pmc Genome-wide significance for a modifier of age at neurological onset in Huntington's disease at 6q23-24: the HD MAPS study
    Jian Liang Li
    Department of Neurology, Boston University School of Medicine, Boston, MA, USA
    BMC Med Genet 7:71. 2006
    ....
  3. pmc Altered neurotransmitter receptor expression in transgenic mouse models of Huntington's disease
    J H Cha
    Department of Neurology, Massachusetts General Hospital, Boston 02114, USA
    Philos Trans R Soc Lond B Biol Sci 354:981-9. 1999
    ..These results suggest that (i) receptor decreases precede, and therefore might contribute to, the development of clinical symptoms, and (ii) altered transcription of specific genes might be a key pathological mechanism in HD...
  4. pmc Transcriptional signatures in Huntington's disease
    Jang Ho J Cha
    MassGeneral Institute for Neurodegenerative Disease, 114 16th Street B114 2000, Charlestown, MA 02129 4404, USA
    Prog Neurobiol 83:228-48. 2007
    ..In the future, gene expression profiling will be used as a readout in clinical trials aimed at correcting transcriptional dysregulation in Huntington's disease...
  5. pmc Finding diamonds in the rubble
    Jang Ho J Cha
    Exp Neurol 205:1-4. 2007
  6. doi Environmental enrichment reduces neuronal intranuclear inclusion load but has no effect on messenger RNA expression in a mouse model of Huntington disease
    Caroline L Benn
    Mass General Institute for Neurodegenerative Disease, Charlestown, Massachusetts, USA
    J Neuropathol Exp Neurol 69:817-27. 2010
    ..Thus, the therapeutic effects of environmental enrichment likely contribute to decreasing aggregated polyglutamine protein levels without exerting strong effects on gene expression...
  7. ncbi Dopamine release is impaired in a mouse model of DYT1 dystonia
    Aygul Balcioglu
    MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
    J Neurochem 102:783-8. 2007
    ..The defect in DA release as observed may contribute to the abnormalities in motor learning as previously documented in this transgenic mouse model, and may contribute to the clinical symptoms of the human disorder...
  8. ncbi Diffusion-weighted magnetic resonance imaging abnormalities in Bartonella encephalopathy
    Aneesh B Singhal
    Department of Neurology, Massachusetts General Hospital, Biogen, Inc MAP, Boston, USA
    J Neuroimaging 13:79-82. 2003
    ..In patients with unexplained, refractory seizures, the presence of DWI abnormalities warrants a search for unusual infectious or inflammatory disorders, like Bartonella encephalitis...
  9. doi Mechanisms of distribution of mouse beta-galactosidase in the adult GM1-gangliosidosis brain
    M L D Broekman
    Department of Neurology, Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Gene Ther 16:303-8. 2009
    ..In addition, we found evidence of axonal transport of vector-encoded mRNA...
  10. ncbi Glutamate receptor dysregulation in the hippocampus of transgenic mice carrying mutated human amyloid precursor protein
    J H Cha
    Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
    Neurobiol Dis 8:90-102. 2001
    ..These data suggest that mutant APP overexpression or age-related amyloid deposition produce a subtle specific alteration in hippocampal glutamate receptors with aging...
  11. pmc Huntingtin modulates transcription, occupies gene promoters in vivo, and binds directly to DNA in a polyglutamine-dependent manner
    Caroline L Benn
    Department of Neurology and Center for Interdisciplinary Informatics, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, Massachusetts 02129 4404, USA
    J Neurosci 28:10720-33. 2008
    ..Together, these findings suggest mutant Htt modulates gene expression through abnormal interactions with genomic DNA, altering DNA conformation and transcription factor binding...
  12. doi Altered histone monoubiquitylation mediated by mutant huntingtin induces transcriptional dysregulation
    Mee Ohk Kim
    MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Neurosci 28:3947-57. 2008
    ..These findings also provide a rationale for targeting histone monoubiquitylation for therapy in HD...
  13. ncbi Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage
    Alexandre Kuhn
    Ecole Polytechnique Federale de Lausanne EPFL, 1015 Lausanne, Switzerland
    Hum Mol Genet 16:1845-61. 2007
    ....
  14. ncbi Histones associated with downregulated genes are hypo-acetylated in Huntington's disease models
    Ghazaleh Sadri-Vakili
    Department of Neurology, MassGeneral Institute for NeurodegenerativeDisease, Massachusetts General Hospital, B114 2000, 114 16th Street, Charlestown, MA 02129 4404, USA
    Hum Mol Genet 16:1293-306. 2007
    ..Nevertheless, treatment with HDAC inhibitors corrects mRNA abnormalities through modification of histone proteins and may prove to be of therapeutic value in HD...
  15. ncbi Increased huntingtin protein length reduces the number of polyglutamine-induced gene expression changes in mouse models of Huntington's disease
    Edmond Y W Chan
    Center for Molecular Medicine and Therapeutics, Department of Medical Genetics, Children s and Women s Hospital, University of British Columbia, Vancouver, British Columbia, Canada, V5H 4H4
    Hum Mol Genet 11:1939-51. 2002
    ..Furthermore, our findings suggest that short N-terminal fragments of mutant htt might be responsible for the gene expression alterations observed in human HD brain...
  16. ncbi Histone deacetylase inhibitors: a novel therapeutic approach to Huntington's disease (complex mechanism of neuronal death)
    Ghazaleh Sadri-Vakili
    Massachusetts General Hospital, MassGeneral Institute for Neurodegenerative Disease, 114 16th Street B114 2001, Charlestown, MA 02129 4404, USA
    Curr Alzheimer Res 3:403-8. 2006
    ..In this review we discuss a number of studies that use HDAC inhibitors as therapeutic agents in HD models. These studies demonstrate that HDAC inhibitors are a promising therapeutic approach for the treatment of HD...
  17. ncbi Sp1 is up-regulated in cellular and transgenic models of Huntington disease, and its reduction is neuroprotective
    Zhihua Qiu
    Massachusetts General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Charlestown, MA 02129, USA
    J Biol Chem 281:16672-80. 2006
    ..Our data suggest that enhancement of transcription factor Sp1 contributes to the pathology of HD and demonstrates that its suppression is beneficial...
  18. ncbi Inhibition of tryptophan hydroxylase activity and decreased 5-HT1A receptor binding in a mouse model of Huntington's disease
    George J Yohrling IV
    Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Neurochem 82:1416-23. 2002
    ..The presymptomatic inhibition of TPH activity in the R6/2 mice may help explain the functional consequences of HD and provide insights into new targets for pharmacotherapy...
  19. ncbi Motor dysfunction and gliosis with preserved dopaminergic markers in human alpha-synuclein A30P transgenic mice
    Teresa Gomez-Isla
    Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA
    Neurobiol Aging 24:245-58. 2003
    ..Thus, high expression of mutant human alpha-synuclein resulted in a progressive motor and widespread CNS gliotic phenotype independent of dopaminergic dysfunction in the Tg5093 line...
  20. ncbi Decreased association of the transcription factor Sp1 with genes downregulated in Huntington's disease
    Alice S Chen-Plotkin
    MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital B114 2000, 114 16th Street, Charlestown, MA 02129 4404, USA
    Neurobiol Dis 22:233-41. 2006
    ..Moreover, the altered binding seen with Sp1 is not found with another transcription factor, NF-Y. These findings suggest that mutant huntingtin dissociates Sp1 from target promoters, inhibiting transcription of specific genes...
  21. ncbi Contribution of nuclear and extranuclear polyQ to neurological phenotypes in mouse models of Huntington's disease
    Caroline L Benn
    King s College London, Medical and Molecular Genetics, GKT School of Medicine, UK
    Hum Mol Genet 14:3065-78. 2005
    ..However, our data suggest that cytoplasmic mutant exon 1 htt, if present, contributes to disease progression...
  22. ncbi Mutant huntingtin increases nuclear corepressor function and enhances ligand-dependent nuclear hormone receptor activation
    George J Yohrling
    Department of Neurology, Center for Aging, Genetics, and Neurodegeneration, Massachusetts General Hospital, Charlestown 02129, USA
    Mol Cell Neurosci 23:28-38. 2003
    ..In vitro binding data shows that TR binds to HD53Q in the presence of ligand. Taken together these data suggest that Htt may function as a transcriptional coactivator of nuclear hormone receptors...
  23. ncbi Analysis of cellular, transgenic and human models of Huntington's disease reveals tyrosine hydroxylase alterations and substantia nigra neuropathology
    George J Yohrling
    Department of Neurology, Center for Aging, Genetics, and Neurodegeneration, Massachusetts General Hospital, 114 16th Street, B114 2000, Charlestown, MA 02129 4404, USA
    Brain Res Mol Brain Res 119:28-36. 2003
    ..These findings implicate abnormalities in dopamine neurotransmission in HD and may provide new insights into targets for pharmacotherapy...
  24. pmc A genome scan for modifiers of age at onset in Huntington disease: The HD MAPS study
    Jian Liang Li
    Department of Neurology, Boston University School of Medicine, and Bioinformatics Program, School of Public Health, Boston University, Boston, MA, USA
    Am J Hum Genet 73:682-7. 2003
    ..Suggestive evidence for linkage was found at 4p16 (LOD=1.93), 6p21-23 (LOD=2.29), and 6q24-26 (LOD=2.28), which may be useful for investigation of genes that modify age at onset of HD...
  25. doi 50bp deletion in the promoter for superoxide dismutase 1 (SOD1) reduces SOD1 expression in vitro and may correlate with increased age of onset of sporadic amyotrophic lateral sclerosis
    Wendy J Broom
    Day Neuromuscular Research Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    Amyotroph Lateral Scler 9:229-37. 2008
    ..Our findings suggest the hypothesis that this deletion reduces expression of the SOD1 gene and that levels of the SOD1 protein may modify the phenotype of SALS within selected populations...
  26. ncbi Neurotransmitter receptor analysis in transgenic mouse models
    Caroline L Benn
    Mass General Institute for Neurodegenerative Disease and Department of Neurolofy, Massachusetts General Hospital, Charlestown, USA
    Methods Mol Biol 277:231-60. 2004
    ..With receptor binding and ISH, one can obtain quantitative region-specific assessments of neurotransmitter receptor alteration, a key pathologic event in HD pathogenesis...
  27. ncbi Chromatin immunoprecipitation technique for study of transcriptional dysregulation in intact mouse brain
    Melissa W Braveman
    Mass General Institute for Neurodegenerative Disease and Department of Neurology, Massachusetts General Hospital, Charlestown, USA
    Methods Mol Biol 277:261-76. 2004
    ..ChIP applied to whole-mouse brain can thus offer a window into mechanisms of transcriptional dysregulation...
  28. pmc The paradigm of Huntington's disease: therapeutic opportunities in neurodegeneration
    Julie Leegwater-Kim
    Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129 4404, USA
    NeuroRx 1:128-38. 2004
    ..HD thus continues to serve as a paradigmatic disorder, with basic bench research generating clinically relevant insights and stimulating the development of therapeutic human trials...
  29. ncbi Mechanisms of disease: Histone modifications in Huntington's disease
    Ghazaleh Sadri-Vakili
    MassGeneral Institute for Neurodegenerative Disease, Boston, MA, USA
    Nat Clin Pract Neurol 2:330-8. 2006
    ..In addition, we discuss how these histone modifications not only lead to pathogenesis, but might also provide a novel therapeutic strategy for treating this devastating disease...

Research Grants9

  1. RECEPTOR GENE TRANSCRIPTION IN HUNTINGTONS DISEASE
    Jang Ho Cha; Fiscal Year: 2002
    ....
  2. RECEPTOR GENE TRANSCRIPTION IN HUNTINGTON'S DISEASE
    Jang Ho Cha; Fiscal Year: 2007
    ..Such fundamental mechanistic information is critical to the eventual development of effective therapy for HD. ..