Nicholas T Seyfried

Summary

Affiliation: Emory University
Country: USA

Publications

  1. pmc A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease
    Nicholas T Seyfried
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA Electronic address
    Cell Syst . 2016
  2. pmc U1 small nuclear ribonucleoproteins (snRNPs) aggregate in Alzheimer's disease due to autosomal dominant genetic mutations and trisomy 21
    Chadwick M Hales
    Department of Neurology, Emory University School of Medicine, Atlanta 30322, Georgia
    Mol Neurodegener 9:15. 2014
  3. pmc Exploring the potential of the platelet membrane proteome as a source of peripheral biomarkers for Alzheimer's disease
    Laura E Donovan
    Department of Neurology and Center for Neurodegenerative Disease, Emory University School of Medicine, 615 Michael Street NE, Atlanta, Georgia 30322, USA
    Alzheimers Res Ther 5:32. 2013
  4. pmc Quantitative analysis of the detergent-insoluble brain proteome in frontotemporal lobar degeneration using SILAC internal standards
    Nicholas T Seyfried
    Department of Biochemistry, Center for Neurodegenerative Disease, School of Medicine, Emory University, Atlanta, Georgia 30322, USA
    J Proteome Res 11:2721-38. 2012
  5. pmc Tissue-type plasminogen activator mediates neuronal detection and adaptation to metabolic stress
    Fang Wu
    Department of Neurology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia, USA
    J Cereb Blood Flow Metab 33:1761-9. 2013
  6. pmc Analysis of a membrane-enriched proteome from postmortem human brain tissue in Alzheimer's disease
    Laura E Donovan
    Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA
    Proteomics Clin Appl 6:201-11. 2012
  7. pmc Multiplex SILAC analysis of a cellular TDP-43 proteinopathy model reveals protein inclusions associated with SUMOylation and diverse polyubiquitin chains
    Nicholas T Seyfried
    Department of Human Genetics, School of Medicine, Emory University, Atlanta, Georgia 30322, USA
    Mol Cell Proteomics 9:705-18. 2010
  8. pmc Asparaginyl endopeptidase cleaves TDP-43 in brain
    Jeremy H Herskowitz
    Department of Neurology, Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA
    Proteomics 12:2455-63. 2012
  9. pmc Coaggregation of RNA-binding proteins in a model of TDP-43 proteinopathy with selective RGG motif methylation and a role for RRM1 ubiquitination
    Eric B Dammer
    Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America
    PLoS ONE 7:e38658. 2012
  10. pmc Phosphoproteomic analysis reveals site-specific changes in GFAP and NDRG2 phosphorylation in frontotemporal lobar degeneration
    Jeremy H Herskowitz
    Department of Neurology, The Center for Neurodegenerative Diseases, Laboratory Medicine, and Proteomics Service Center, Emory University School of Medicine, Atlanta, Georgia 30322, United States
    J Proteome Res 9:6368-79. 2010

Collaborators

Detail Information

Publications35

  1. pmc A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease
    Nicholas T Seyfried
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA Electronic address
    Cell Syst . 2016
    ..This multi-network analysis reveals protein- and disease-specific pathways involved in the etiology, initiation, and progression of AD...
  2. pmc U1 small nuclear ribonucleoproteins (snRNPs) aggregate in Alzheimer's disease due to autosomal dominant genetic mutations and trisomy 21
    Chadwick M Hales
    Department of Neurology, Emory University School of Medicine, Atlanta 30322, Georgia
    Mol Neurodegener 9:15. 2014
    ..However little is known about snRNP biology in early onset AD due to autosomal dominant genetic mutations or trisomy 21 in Down syndrome. Therefore we investigated snRNP biochemical and pathologic features in these disorders...
  3. pmc Exploring the potential of the platelet membrane proteome as a source of peripheral biomarkers for Alzheimer's disease
    Laura E Donovan
    Department of Neurology and Center for Neurodegenerative Disease, Emory University School of Medicine, 615 Michael Street NE, Atlanta, Georgia 30322, USA
    Alzheimers Res Ther 5:32. 2013
    ..Given parallels between neuron and platelet biology, we hypothesized platelet membrane-associated protein changes may differentiate patients clinically defined with probable AD from noncognitive impaired controls...
  4. pmc Quantitative analysis of the detergent-insoluble brain proteome in frontotemporal lobar degeneration using SILAC internal standards
    Nicholas T Seyfried
    Department of Biochemistry, Center for Neurodegenerative Disease, School of Medicine, Emory University, Atlanta, Georgia 30322, USA
    J Proteome Res 11:2721-38. 2012
    ..However, in a subset of FTLD cases, PSF was aberrantly localized to the cytoplasm of oligodendrocytes. These data raise the possibility that PSF directed RNA processes in oligodendrocytes are altered in neurodegenerative disease...
  5. pmc Tissue-type plasminogen activator mediates neuronal detection and adaptation to metabolic stress
    Fang Wu
    Department of Neurology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia, USA
    J Cereb Blood Flow Metab 33:1761-9. 2013
    ..These data indicate that the release of neuronal tPA or treatment with rtPA activate a cell signaling pathway in the synaptic space that promotes the detection and adaptation to metabolic stress. ..
  6. pmc Analysis of a membrane-enriched proteome from postmortem human brain tissue in Alzheimer's disease
    Laura E Donovan
    Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA
    Proteomics Clin Appl 6:201-11. 2012
    ..This study aims to validate a method to identify new proteins that could be involved in the pathogenesis of AD and potentially serve as disease biomarkers...
  7. pmc Multiplex SILAC analysis of a cellular TDP-43 proteinopathy model reveals protein inclusions associated with SUMOylation and diverse polyubiquitin chains
    Nicholas T Seyfried
    Department of Human Genetics, School of Medicine, Emory University, Atlanta, Georgia 30322, USA
    Mol Cell Proteomics 9:705-18. 2010
    ....
  8. pmc Asparaginyl endopeptidase cleaves TDP-43 in brain
    Jeremy H Herskowitz
    Department of Neurology, Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA
    Proteomics 12:2455-63. 2012
    ..Moreover, these data highlight the utility of combining proteomic strategies in vitro and in vivo to provide insight into TDP-43 biology that will fuel the design of more detailed models of disease pathogenesis...
  9. pmc Coaggregation of RNA-binding proteins in a model of TDP-43 proteinopathy with selective RGG motif methylation and a role for RRM1 ubiquitination
    Eric B Dammer
    Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America
    PLoS ONE 7:e38658. 2012
    ..Together, these findings define some of the aggregation partners of TDP-43, and suggest that TDP-43 ubiquitination influences TDP-43 oligomerization...
  10. pmc Phosphoproteomic analysis reveals site-specific changes in GFAP and NDRG2 phosphorylation in frontotemporal lobar degeneration
    Jeremy H Herskowitz
    Department of Neurology, The Center for Neurodegenerative Diseases, Laboratory Medicine, and Proteomics Service Center, Emory University School of Medicine, Atlanta, Georgia 30322, United States
    J Proteome Res 9:6368-79. 2010
    ..These data highlight the utility of combining proteomic and phosphoproteomic strategies to characterize post-mortem human brain tissue...
  11. pmc Polyubiquitin linkage profiles in three models of proteolytic stress suggest the etiology of Alzheimer disease
    Eric B Dammer
    Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Biol Chem 286:10457-65. 2011
    ..We conclude that different polyUb linkages play distinct roles under the three proteolytic stress conditions, and protein folding capacity in the heat shock responsive pathway might be more affected in Alzheimer disease...
  12. doi request reprint Changes in the detergent-insoluble brain proteome linked to amyloid and tau in Alzheimer's Disease progression
    Chadwick M Hales
    Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA
    Proteomics 16:3042-3053. 2016
    ..Thus, proteins that cross-correlate with both Aβ and tau, including specific U1 snRNPs, may have potential mechanistic roles in linking Aβ plaques to tau tangle pathology during AD progression...
  13. pmc Aggregates of small nuclear ribonucleic acids (snRNAs) in Alzheimer's disease
    Chadwick M Hales
    Center for Neurodegenerative Disease, Emory University, Atlanta, GA Department of Neurology, Emory University School of Medicine, Atlanta, GA
    Brain Pathol 24:344-51. 2014
    ..In combination with our previous results, these findings demonstrate that aggregates of U1 snRNA and U1 small nuclear ribonucleoproteins represent a new pathological hallmark of AD. ..
  14. pmc Pharmacologic inhibition of ROCK2 suppresses amyloid-β production in an Alzheimer's disease mouse model
    Jeremy H Herskowitz
    Center for Neurodegenerative Disease, and Departments of Neurology, Cell Biology, and Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, Medicinal Chemistry, Translational Research Institute, The Scripps Research Institute, Jupiter, Florida 33458, Department of Pathology, University of Washington, Seattle, Washington 98104, Departments of Pathology and Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, and Unit of Clinical and Translational Neuroscience and Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, Maryland 21224
    J Neurosci 33:19086-98. 2013
    ..Collectively, these findings highlight ROCK2 as a mechanism-based therapeutic target to combat Aβ production in AD. ..
  15. pmc Neuron enriched nuclear proteome isolated from human brain
    Eric B Dammer
    Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Proteome Res 12:3193-206. 2013
    ..These comparative proteomic data sets also reveal a number of transcription and splicing factors that are selectively enriched in a cell-type-specific manner in human brain. ..
  16. pmc CSF complement 3 and factor H are staging biomarkers in Alzheimer's disease
    William T Hu
    Department of Neurology, Emory University School of Medicine, 615 Michael Street, 505 F, Atlanta, GA, 30322, USA
    Acta Neuropathol Commun 4:14. 2016
    ..We hypothesized that levels of C3 and associated factor H (FH) can potentially distinguish between mild cognitive impairment (MCI) and dementia stages of AD, but we also found their levels to be influenced by age and disease status...
  17. pmc Abnormal gephyrin immunoreactivity associated with Alzheimer disease pathologic changes
    Chadwick M Hales
    From the Department of Neurology CMH, HR, AIL, JJL, TSW, Center for Neurodegenerative Disease CMH, HR, NTS, EBD, DMD, MG, AIL, JJL, TSW, Departments of Biochemistry NTS and Human Genetics EBD, TSW, and Pathology and Laboratory Medicine MG, Emory University School of Medicine, Atlanta, Georgia Department of Pathology, University of Washington, Seattle, Washington TJM Departments of Pathology and Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland JCT National Institute of Aging, National Institutes of Health, Bethesda, Maryland MT and Atlanta Veterans Administration Medical Center, Atlanta, Georgia TSW
    J Neuropathol Exp Neurol 72:1009-15. 2013
    ..Because gephyrin is involved in synaptic organization and synaptic dysfunction is an early event in AD, these findings point to its possible role in the pathogenesis of AD. ..
  18. pmc Aberrant septin 11 is associated with sporadic frontotemporal lobar degeneration
    Yair M Gozal
    Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA
    Mol Neurodegener 6:82. 2011
    ....
  19. pmc ATRIP Deacetylation by SIRT2 Drives ATR Checkpoint Activation by Promoting Binding to RPA-ssDNA
    Hui Zhang
    Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA
    Cell Rep 14:1435-47. 2016
    ....
  20. pmc Delta-secretase cleaves amyloid precursor protein and regulates the pathogenesis in Alzheimer's disease
    Zhentao Zhang
    Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Nat Commun 6:8762. 2015
    ..Blockade of APP cleavage by AEP in mice alleviates pathological and behavioural deficits. Thus, AEP acts as a δ-secretase, contributing to the age-dependent pathogenic mechanisms in AD. ..
  21. pmc Quantitative phosphoproteomics of Alzheimer's disease reveals cross-talk between kinases and small heat shock proteins
    Eric B Dammer
    Department of Biochemistry, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA, USA
    Proteomics 15:508-19. 2015
    ..We further identified a network of phosphorylated kinases, which coenriched with phosphorylated small HSPs. This supports a hypothesis that a number of kinases are regulating and/or regulated by the small HSP folding network. ..
  22. pmc Rho kinase II phosphorylation of the lipoprotein receptor LR11/SORLA alters amyloid-beta production
    Jeremy H Herskowitz
    Department of Neurology, The Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Biol Chem 286:6117-27. 2011
    ..These findings provide direct evidence that LR11 is phosphorylated in vivo and indicate that ROCK2 phosphorylation of LR11 may enhance LR11 mediated processing of APP and amyloid production...
  23. pmc Aggregation properties of the small nuclear ribonucleoprotein U1-70K in Alzheimer disease
    Ian Diner
    From the Departments of Biochemistry and the Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322
    J Biol Chem 289:35296-313. 2014
    ..Our results support a hypothesis that aberrant forms of U1-70K in AD can directly sequester soluble forms of U1-70K into insoluble aggregates. ..
  24. pmc Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation
    Ping Xu
    Department of Human Genetics, Center for Neurodegenerative Diseases, Emory University, Atlanta, GA 30322, USA
    Cell 137:133-45. 2009
    ..Ubc6 primarily synthesizes K11-linked chains, and K11 linkages function in the ERAD pathway. Thus, unconventional polyubiquitin chains are critical for ubiquitin-proteasome system function...
  25. pmc Consequences of impaired purine recycling on the proteome in a cellular model of Lesch-Nyhan disease
    Eric B Dammer
    Department of Biochemistry, Emory University, Atlanta, GA, USA
    Mol Genet Metab 114:570-9. 2015
    ..Other pathways were not anticipated, disclosing previously unknown connections with purine metabolism and novel insights into the pathogenesis of LND. ..
  26. pmc Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in Alzheimer's disease
    Zhentao Zhang
    1 Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA 2 Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
    Nat Med 20:1254-62. 2014
    ..Together, these observations indicate that AEP acts as a crucial mediator of tau-related clinical and neuropathological changes. Inhibition of AEP may be therapeutically useful for treating tau-mediated neurodegenerative diseases. ..
  27. pmc Expression, purification and proteomic analysis of recombinant histone H4 acetylated at lysine 16
    Satish Kallappagoudar
    Department of Biology, Emory University, Atlanta, GA 30322, USA
    Proteomics 13:1687-91. 2013
    ..coli and on preventing the premature decay of the H4 mRNA. These modifications to the original procedure render it easily applicable to the generation of any covalently modified histone H4 isoform...
  28. pmc The Evolutionarily-conserved Polyadenosine RNA Binding Protein, Nab2, Cooperates with Splicing Machinery to Regulate the Fate of pre-mRNA
    Sharon Soucek
    Graduate Program in Biochemistry, Cell, and Developmental Biology, Emory University School of Medicine, Atlanta, GA, USA Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA
    Mol Cell Biol . 2016
    ....
  29. pmc Osteopontin Is a Blood Biomarker for Microglial Activation and Brain Injury in Experimental Hypoxic-Ischemic Encephalopathy
    Yikun Li
    Department of Pediatrics, Emory University School of Medicine, and Children s Healthcare of Atlanta, Atlanta, GA 30322
    Eneuro 4:. 2017
    ..Plasma OPN levels at 48 h post-HI also parallel the severity of brain damage at 7-d recovery. Together, these results suggest that OPN may be a prognostic blood biomarker in HIE through monitoring brain microglial activation...
  30. pmc Pseudomonas aeruginosa EftM Is a Thermoregulated Methyltransferase
    Joshua P Owings
    From the Department of Pediatrics, Division of Pulmonology, Allergy Immunology, Cystic Fibrosis and Sleep and the Emory Children s Center for Cystic Fibrosis Research, Emory University and Children s Healthcare of Atlanta, Atlanta, Georgia 30322, The Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia 22908
    J Biol Chem 291:3280-90. 2016
    ..Collectively, our results show that EftM is a thermolabile, SAM-dependent methyltransferase that directly trimethylates lysine 5 of EF-Tu in P. aeruginosa. ..
  31. pmc Systematic approach for validating the ubiquitinated proteome
    Nicholas T Seyfried
    Department of Human Genetics, Center for Neurodegenerative Diseases, Emory University, Atlanta, Georgia 30322, USA
    Anal Chem 80:4161-9. 2008
    ..A second independent analysis indicated that the method can be simplified by excising fewer than ten gel bands. Therefore, this strategy establishes criteria necessary for the interpretation of ubiquitinated proteins...
  32. pmc Cellular O-Glycome Reporter/Amplification to explore O-glycans of living cells
    Matthew R Kudelka
    Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA
    Nat Methods 13:81-6. 2016
    ..Furthermore, when coupled with computational modeling, CORA can be used for predictions about the diversity of the human O-glycome and offers new opportunities to identify novel glycan biomarkers for human diseases. ..
  33. pmc Stress induces p38 MAPK-mediated phosphorylation and inhibition of Drosha-dependent cell survival
    Qian Yang
    Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi an, Shaanxi 710038, China Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA Electronic address
    Mol Cell 57:721-34. 2015
    ..In contrast, increase in Drosha attenuates stress-induced death. These findings reveal a critical regulatory mechanism by which stress engages p38 MAPK pathway to destabilize Drosha and inhibit Drosha-mediated cellular survival. ..
  34. pmc SIRT2 directs the replication stress response through CDK9 deacetylation
    Hui Zhang
    Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA
    Proc Natl Acad Sci U S A 110:13546-51. 2013
    ....
  35. pmc Tissue-type plasminogen activator regulates the neuronal uptake of glucose in the ischemic brain
    Fang Wu
    Department of Neurology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Neurosci 32:9848-58. 2012
    ..Our data indicate that tPA activates a cell signaling pathway that allows neurons to sense and adapt to oxygen and glucose deprivation...