Michael K Lee

Summary

Affiliation: Johns Hopkins University
Country: USA

Publications

  1. ncbi request reprint Parkinson's disease alpha-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death
    Lee J Martin
    Division of Neuropathology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 2196, USA
    J Neurosci 26:41-50. 2006
  2. ncbi request reprint Inclusion body formation and neurodegeneration are parkin independent in a mouse model of alpha-synucleinopathy
    Rainer von Coelln
    Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 26:3685-96. 2006
  3. pmc Human alpha-synuclein-harboring familial Parkinson's disease-linked Ala-53 --> Thr mutation causes neurodegenerative disease with alpha-synuclein aggregation in transgenic mice
    Michael K Lee
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 2196, USA
    Proc Natl Acad Sci U S A 99:8968-73. 2002
  4. pmc Ubiquitin proteasome system stress underlies synergistic killing of ovarian cancer cells by bortezomib and a novel HDAC6 inhibitor
    Martina Bazzaro
    Department of Pathology, The Johns Hopkins University, Baltimore, Maryland 21231, USA
    Clin Cancer Res 14:7340-7. 2008
  5. pmc Synphilin-1 attenuates neuronal degeneration in the A53T alpha-synuclein transgenic mouse model
    Wanli W Smith
    Division of Neurobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Hum Mol Genet 19:2087-98. 2010
  6. pmc Resistance to MPTP-neurotoxicity in α-synuclein knockout mice is complemented by human α-synuclein and associated with increased β-synuclein and Akt activation
    Bobby Thomas
    Neuroregeneration and Stem Cell Programs, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
    PLoS ONE 6:e16706. 2011
  7. ncbi request reprint Alpha-synuclein phosphorylation enhances eosinophilic cytoplasmic inclusion formation in SH-SY5Y cells
    Wanli W Smith
    Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 25:5544-52. 2005
  8. ncbi request reprint Abeta deposition is associated with enhanced cortical alpha-synuclein lesions in Lewy body diseases
    Olga Pletnikova
    Department of Pathology Neuropathology, Johns Hopkins University School of Medicine, Ross Building 558, Baltimore, MD 21205, USA
    Neurobiol Aging 26:1183-92. 2005
  9. pmc Aggregation promoting C-terminal truncation of alpha-synuclein is a normal cellular process and is enhanced by the familial Parkinson's disease-linked mutations
    Wenxue Li
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 102:2162-7. 2005
  10. ncbi request reprint Amyloid pathology is associated with progressive monoaminergic neurodegeneration in a transgenic mouse model of Alzheimer's disease
    Ying Liu
    Department of Pathology, Johns Hopkins University, Baltimore, Maryland 21205, USA
    J Neurosci 28:13805-14. 2008

Research Grants

Collaborators

Detail Information

Publications26

  1. ncbi request reprint Parkinson's disease alpha-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death
    Lee J Martin
    Division of Neuropathology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 2196, USA
    J Neurosci 26:41-50. 2006
    ..Thus, A53T mutant mice develop intraneuronal inclusions, mitochondrial DNA damage and degeneration, and apoptotic-like death of neocortical, brainstem, and motor neurons...
  2. ncbi request reprint Inclusion body formation and neurodegeneration are parkin independent in a mouse model of alpha-synucleinopathy
    Rainer von Coelln
    Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 26:3685-96. 2006
    ....
  3. pmc Human alpha-synuclein-harboring familial Parkinson's disease-linked Ala-53 --> Thr mutation causes neurodegenerative disease with alpha-synuclein aggregation in transgenic mice
    Michael K Lee
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 2196, USA
    Proc Natl Acad Sci U S A 99:8968-73. 2002
    ..Further, alpha-Syn-dependent neurodegeneration is associated with abnormal accumulation of detergent-insoluble alpha-Syn...
  4. pmc Ubiquitin proteasome system stress underlies synergistic killing of ovarian cancer cells by bortezomib and a novel HDAC6 inhibitor
    Martina Bazzaro
    Department of Pathology, The Johns Hopkins University, Baltimore, Maryland 21231, USA
    Clin Cancer Res 14:7340-7. 2008
    ....
  5. pmc Synphilin-1 attenuates neuronal degeneration in the A53T alpha-synuclein transgenic mouse model
    Wanli W Smith
    Division of Neurobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Hum Mol Genet 19:2087-98. 2010
    ..These studies demonstrate that synphilin-1 can diminish the severity of alpha-synucleinopathy and play a neuroprotective role against A53T alpha-synuclein toxicity in vivo...
  6. pmc Resistance to MPTP-neurotoxicity in α-synuclein knockout mice is complemented by human α-synuclein and associated with increased β-synuclein and Akt activation
    Bobby Thomas
    Neuroregeneration and Stem Cell Programs, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
    PLoS ONE 6:e16706. 2011
    ..Together these findings provide new mechanistic insights on the role α-synuclein in modulating neurodegenerative phenotypes by regulation of Akt-mediated cell survival signaling in vivo...
  7. ncbi request reprint Alpha-synuclein phosphorylation enhances eosinophilic cytoplasmic inclusion formation in SH-SY5Y cells
    Wanli W Smith
    Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 25:5544-52. 2005
    ..These results indicate that phosphorylation of alpha-synuclein at S129 may be important for the formation of inclusions in PD and related alpha synucleinopathies...
  8. ncbi request reprint Abeta deposition is associated with enhanced cortical alpha-synuclein lesions in Lewy body diseases
    Olga Pletnikova
    Department of Pathology Neuropathology, Johns Hopkins University School of Medicine, Ross Building 558, Baltimore, MD 21205, USA
    Neurobiol Aging 26:1183-92. 2005
    ..This suggests that Abeta enhances the development of cortical alpha-synuclein lesions in cases of PD...
  9. pmc Aggregation promoting C-terminal truncation of alpha-synuclein is a normal cellular process and is enhanced by the familial Parkinson's disease-linked mutations
    Wenxue Li
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 102:2162-7. 2005
    ..Collectively, our results indicate that the biology behind the generation and accumulation of alpha-SynDeltaC is likely to have relevance for the initiation and the progression of alpha-Syn aggregation in vivo...
  10. ncbi request reprint Amyloid pathology is associated with progressive monoaminergic neurodegeneration in a transgenic mouse model of Alzheimer's disease
    Ying Liu
    Department of Pathology, Johns Hopkins University, Baltimore, Maryland 21205, USA
    J Neurosci 28:13805-14. 2008
    ..Our results show that a transgenic mouse model of Abeta pathology develops progressive MAergic neurodegeneration occurring in AD cases...
  11. ncbi request reprint Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase
    Joanna L Jankowsky
    Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Hum Mol Genet 13:159-70. 2004
    ..These data suggest that PS1 variants do not simply alter the preferred cleavage site for gamma-secretase, but rather that they have more complex effects on the regulation of gamma-secretase and its access to substrates...
  12. pmc Neurodegenerative phenotypes in an A53T α-synuclein transgenic mouse model are independent of LRRK2
    João Paulo L Daher
    Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Hum Mol Genet 21:2420-31. 2012
    ..These observations fail to provide support for a pathophysiological interaction of LRRK2 and α-synuclein in vivo, at least within neurons of the mouse hindbrain...
  13. pmc Endoplasmic reticulum stress is important for the manifestations of α-synucleinopathy in vivo
    Emanuela Colla
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 32:3306-20. 2012
    ..Attenuating chronic ERS could be an effective therapy for PD and other α-synucleinopathies...
  14. ncbi request reprint Antiapoptotic property of human alpha-synuclein in neuronal cell lines is associated with the inhibition of caspase-3 but not caspase-9 activity
    Wenxue Li
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurochem 93:1542-50. 2005
    ..We conclude that Hualpha-Syn modulates the activity of cleaved caspase-3 product in neuronal cell lines...
  15. ncbi request reprint Stabilization of alpha-synuclein protein with aging and familial parkinson's disease-linked A53T mutation
    Wenxue Li
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 2196, USA
    J Neurosci 24:7400-9. 2004
    ....
  16. pmc Myosin II co-chaperone general cell UNC-45 overexpression is associated with ovarian cancer, rapid proliferation, and motility
    Martina Bazzaro
    Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA
    Am J Pathol 171:1640-9. 2007
    ..In sum, these findings implicate elevated GC UNC-45 protein expression in ovarian carcinoma proliferation and metastasis...
  17. pmc Accumulation of toxic α-synuclein oligomer within endoplasmic reticulum occurs in α-synucleinopathy in vivo
    Emanuela Colla
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 32:3301-5. 2012
    ..These results indicate that αS oligomers with toxic conformation accumulate in ER, and αS oligomer-dependent ER stress is pathologically relevant for PD...
  18. pmc Passive (amyloid-β) immunotherapy attenuates monoaminergic axonal degeneration in the AβPPswe/PS1dE9 mice
    Ying Liu
    Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
    J Alzheimers Dis 23:271-9. 2011
    ..Our results demonstrate that lowering of Aβ levels via passive Aβ immunotherapy ameliorates ongoing degenerative processes, supporting a causal link between Aβ and neurodegeneration...
  19. pmc Differential regulation of small heat shock proteins in transgenic mouse models of neurodegenerative diseases
    Jiou Wang
    Department of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Room 558, Baltimore, MD 21205, USA
    Neurobiol Aging 29:586-97. 2008
    ..The transgenes in these mice are expressed highly in astrocytes and thus our results suggest a role for small heat shock proteins in protecting activated glial cells such as astrocytes in neurodegenerative diseases...
  20. ncbi request reprint Axonal transport of human alpha-synuclein slows with aging but is not affected by familial Parkinson's disease-linked mutations
    Wenxue Li
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 2196, USA
    J Neurochem 88:401-10. 2004
    ..Because the rate of axonal transport affects the stability and accumulation of proteins in axons, age-dependent-slowing alpha-Syn is a likely contributor to axonal aggregation of alpha-Syn in alpha-synucleinopathy...
  21. ncbi request reprint Ubiquitin-proteasome system stress sensitizes ovarian cancer to proteasome inhibitor-induced apoptosis
    Martina Bazzaro
    Department of Pathology, The Johns Hopkins School of Medicine, Cancer Research Building 2, 1550 Orleans Street, Baltimore, MD 21231, USA
    Cancer Res 66:3754-63. 2006
    ..In sum, elevated proliferation and metabolic rate resulting from malignant transformation of the epithelium stresses the UPS and renders ovarian carcinoma more sensitive to apoptosis in response to proteasomal inhibition...
  22. ncbi request reprint Association of DJ-1 and parkin mediated by pathogenic DJ-1 mutations and oxidative stress
    Darren J Moore
    Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Hum Mol Genet 14:71-84. 2005
    ..These data potentially link DJ-1 and parkin in a common molecular pathway at multiple levels that may have important implications for understanding the pathogenesis of inherited and sporadic PD...
  23. ncbi request reprint Accumulation of proteolytic fragments of mutant presenilin 1 and accelerated amyloid deposition are co-regulated in transgenic mice
    David R Borchelt
    Department of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Ave, Baltimore, MD 21205, USA
    Neurobiol Aging 23:171-7. 2002
    ....
  24. ncbi request reprint Wild-type and mutant alpha-synuclein induce a multi-component gene expression profile consistent with shared pathophysiology in different transgenic mouse models of PD
    Renee M Miller
    Center for Aging and Developmental Biology, Aab Institute for Biomedical Research, Rochester, NY 14642, USA
    Exp Neurol 204:421-32. 2007
    ..Analysis of mutant alpha-synuclein mice at a time point when pathology is advanced reveals several new candidate genes that may play a role in neuronal demise and/or protein accumulation...
  25. ncbi request reprint Lysine 63-linked ubiquitination promotes the formation and autophagic clearance of protein inclusions associated with neurodegenerative diseases
    Jeanne M M Tan
    Neurodegeneration Research Lab, National Neuroscience Institute, Singapore, Singapore
    Hum Mol Genet 17:431-9. 2008
    ..Collectively, our results provide a novel mechanistic route that underlies the life cycle of an inclusion body. Harnessing this pathway may offer innovative approaches in the treatment of neurodegenerative disorders...
  26. ncbi request reprint Locomotor hyperactivity and alterations in dopamine neurotransmission are associated with overexpression of A53T mutant human alpha-synuclein in mice
    Erica L Unger
    Huck Institutes for the Life Sciences, The Pennsylvania State University, University Park, 201 Life Sciences Building, University Park, PA 16802, USA
    Neurobiol Dis 21:431-43. 2006
    ..Thus, expression of A53T mutant human alpha-synuclein in mice results in adult-onset hyperactivity associated with D1 receptor and dopamine transporter-mediated alterations in dopamine neurotransmission...

Research Grants3

  1. Preclinical Evaluation of Celastrol, an Inducer of HSP, in alpha-Syn Tg mice
    Michael Lee; Fiscal Year: 2007
    ..We will determine whether increase in heat shock proteins, via administration of novel compound celastrol, can prevent neurodegeneration in mammalian animal models that are directly relevant to PD. ..
  2. Conditional Uch-L1 knockout mice
    Michael Lee; Fiscal Year: 2005
    ..The IoxP-targeted Uch1 mice will be mated to pTH-Cre transgenic mice to silence Uch-L1 expression only in the dopaminergic and noradrenergic neurons. ..