Research Topics
Genomes and Genes
| Lian LiSummaryAffiliation: Emory University Country: USA Publications
Research Grants
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Detail Information
Publications
The molecular machinery of synaptic vesicle exocytosisL Li
Department of Pharmacology, Center for Neurodegenerative Disease, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322 3090, USA
Cell Mol Life Sci 60:942-60. 2003..This review summarizes present knowledge about the molecular mechanisms by which these components mediate and/or regulate synaptic vesicle exocytosis...
Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseasesJoungil Choi
Department of Pharmacology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322, USA
J Biol Chem 281:10816-24. 2006..Our study provides new insights into the oxidative modifications of DJ-1 and indicates association of oxidative damage to DJ-1 with sporadic PD and AD...
Hypertonia-associated protein Trak1 is a novel regulator of endosome-to-lysosome traffickingElizabeth Webber
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322 4218, USA
J Mol Biol 382:638-51. 2008..Our findings support a role for Trak1 in the regulation of Hrs-mediated endosomal sorting and have important implications for understanding hypertonia associated with neurological disorders...
Spongiform neurodegeneration-associated E3 ligase Mahogunin ubiquitylates TSG101 and regulates endosomal traffickingBong Yoon Kim
Department of Pharmacology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA
Mol Biol Cell 18:1129-42. 2007..Our findings support a role for Mahogunin in a proteasome-independent ubiquitylation pathway and suggest a link between dysregulation of endosomal trafficking and spongiform neurodegeneration...
Proteomic analysis reveals Hrs ubiquitin-interacting motif-mediated ubiquitin signaling in multiple cellular processesJulia W Pridgeon
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA
FEBS J 276:118-31. 2009....
Phosphorylation of parkin by Parkinson disease-linked kinase PINK1 activates parkin E3 ligase function and NF-kappaB signalingDi Sha
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA
Hum Mol Genet 19:352-63. 2010..Our findings support a direct link between PINK1-mediated phosphorylation and parkin-mediated ubiquitin signaling and implicate the deregulation of the PINK1/parkin/NF-kappaB neuroprotective signaling pathway in the pathogenesis of PD...
Printor, a novel torsinA-interacting protein implicated in dystonia pathogenesisLisa M Giles
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
J Biol Chem 284:21765-75. 2009..Our findings suggest that printor is a new component of the DYT1 pathogenic pathway and provide a potential molecular target for therapeutic intervention in dystonia...
GRIF1 binds Hrs and is a new regulator of endosomal traffickingElizabeth Kirk
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA
J Cell Sci 119:4689-701. 2006..Our findings suggest that GRIF1 may also participate in microtubule-based transport of early endosomes by acting as an adaptor linking Hrs-containing endosomes to kinesin...
PINK1 protects against oxidative stress by phosphorylating mitochondrial chaperone TRAP1Julia W Pridgeon
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia, United States of America
PLoS Biol 5:e172. 2007..Our findings suggest a novel pathway by which PINK1 phosphorylates downstream effector TRAP1 to prevent oxidative-stress-induced apoptosis and implicate the dysregulation of this mitochondrial pathway in PD pathogenesis...
Mutations associated with Charcot-Marie-Tooth disease cause SIMPLE protein mislocalization and degradation by the proteasome and aggresome-autophagy pathwaysSamuel M Lee
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA
J Cell Sci 124:3319-31. 2011....
Parkinson disease protein DJ-1 converts from a zymogen to a protease by carboxyl-terminal cleavageJue Chen
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322 3090, USA
Hum Mol Genet 19:2395-408. 2010..Our findings support a role for DJ-1 protease in cellular defense against oxidative stress and have important implications for understanding and treating PD...
Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6James A Olzmann
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA
J Cell Biol 178:1025-38. 2007....
Neuroprotection by selective allosteric potentiators of the EP2 prostaglandin receptorJianxiong Jiang
Department of Pharmacology, Emory Chemical Biology Discovery Center, Emory University, Atlanta, GA 30322, USA
Proc Natl Acad Sci U S A 107:2307-12. 2010..Our results strongly reinforce the notion that activation of EP2 receptors by endogenous PGE(2) released in a cell-injury setting is neuroprotective...
Selective enrichment of DJ-1 protein in primate striatal neuronal processes: implications for Parkinson's diseaseJames A Olzmann
Department of Pharmacology, Emory University, Atlanta, Georgia 30322, USA
J Comp Neurol 500:585-99. 2007..Together, these findings indicate neuronal and synaptic expression of DJ-1 in primate subcortical brain regions and suggest a physiological role for DJ-1 in the survival and/or function of nigral-striatal neurons...
Cancer and virus leads by HTS, chemical design and SEA data miningPahk Thepchatri
Chemical Biology Discovery Center, 1510 Clifton Road, Emory University, Atlanta, GA 30322, USA
Curr Top Med Chem 9:1159-71. 2009..In parallel with HTS, a unique component of the Emory virtual screening (VS) effort, namely, substructure enrichment analysis (SEA) program has been utilized in several cases...
Oxidative modifications and aggregation of Cu,Zn-superoxide dismutase associated with Alzheimer and Parkinson diseasesJoungil Choi
Department of Pharmacology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322-3090, USA
J Biol Chem 280:11648-55. 2005..This work suggests that AD, PD, and ALS may share a common or overlapping pathogenic mechanism(s) that could potentially be targeted by similar therapeutic strategies...
Ubiquitination of alpha-synuclein by Siah-1 promotes alpha-synuclein aggregation and apoptotic cell deathJames T Lee
Department of Pharmacology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322 3090, USA
Hum Mol Genet 17:906-17. 2008..Our findings suggest that Siah-1-mediated alpha-synuclein ubiquitination may play a critical role in Lewy body formation and PD pathogenesis...
Parkin-mediated ubiquitin signalling in aggresome formation and autophagyLih Shen Chin
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA
Biochem Soc Trans 38:144-9. 2010..The present review summarizes the current knowledge of the aggresome-autophagy pathway, its regulation by parkin-mediated Lys(63)-linked polyubiquitination, and its dysfunction in neurodegenerative diseases...
TorsinA protein degradation and autophagy in DYT1 dystoniaLisa M Giles
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322 3090, USA
Autophagy 5:82-4. 2009....
Distinct growth factor-induced dynamic mass redistribution (DMR) profiles for monitoring oncogenic signaling pathways in various cancer cellsYuhong Du
Departments of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
J Recept Signal Transduct Res 29:182-94. 2009..5). This technology is applicable to other oncogenic pathways for the discovery of novel therapeutic agents for the treatment of various cancers...
Synthesis and SAR study of N-(4-hydroxy-3-(2-hydroxynaphthalene-1-yl)phenyl)-arylsulfonamides: heat shock protein 90 (Hsp90) inhibitors with submicromolar activity in an in vitro assayThota Ganesh
Chemical Biology Discovery Center, Emory University, 1510 Clifton Road, Atlanta, GA 30322, USA
Bioorg Med Chem Lett 18:4982-7. 2008..In this report, we present a new and general method for the synthesis of a variety of analogs around this scaffold, and discuss their structure-activity relationships...
A dual-readout F2 assay that combines fluorescence resonance energy transfer and fluorescence polarization for monitoring bimolecular interactionsYuhong Du
Department of Pharmacology and Emory Chemical Biology Discovery Center, Emory University School of Medicine, Atlanta, Georgia, USA
Assay Drug Dev Technol 9:382-93. 2011..This strategy can be generally extended to other FP-based assays and is expected to enrich primary HTS information and enhance the hit quality of HTS campaigns...
The ubiquitin-proteasome system in spongiform degenerative disordersBRANDI R WHATLEY
Department of Pharmacology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA
Biochim Biophys Acta 1782:700-12. 2008....
Dystonia-associated mutations cause premature degradation of torsinA protein and cell-type-specific mislocalization to the nuclear envelopeLisa M Giles
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322 3090, USA
Hum Mol Genet 17:2712-22. 2008....
Oxidative modifications and down-regulation of ubiquitin carboxyl-terminal hydrolase L1 associated with idiopathic Parkinson's and Alzheimer's diseasesJoungil Choi
Department of Pharmacology, Center for Neurodegenerative Disease, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
J Biol Chem 279:13256-64. 2004..Together, these results provide evidence supporting a direct link between oxidative damage to the neuronal ubiquitination/de-ubiquitination machinery and the pathogenesis of sporadic AD and PD...
Familial Parkinson's disease-associated L166P mutation disrupts DJ-1 protein folding and functionJames A Olzmann
Departments of Pharmacology, Biochemistry, and Neurology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322 3090, USA
J Biol Chem 279:8506-15. 2004..Together these findings provide insights into the molecular mechanism by which loss-of-function mutations in DJ-1 lead to Parkinson's disease...
Staring, a novel E3 ubiquitin-protein ligase that targets syntaxin 1 for degradationLih Shen Chin
Department of Pharmacology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322 3090, USA
J Biol Chem 277:35071-9. 2002..These findings suggest that Staring is a novel E3 ubiquitin-protein ligase that targets syntaxin 1 for degradation by the ubiquitin-proteasome pathway...
Charcot-Marie-Tooth disease-linked protein SIMPLE functions with the ESCRT machinery in endosomal traffickingSamuel M Lee
Department of Pharmacology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322
J Cell Biol 199:799-816. 2012..Our findings indicate a function of SIMPLE as a regulator of endosomal trafficking and provide evidence linking dysregulated endosomal trafficking to CMT pathogenesis...
Protein misfolding and clearance in demyelinating peripheral neuropathies: Therapeutic implicationsSamuel M Lee
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA USA
Commun Integr Biol 5:107-10. 2012..These studies suggest that targeting protein quality control systems involved in cytoprotection against CMT-associated misfolded proteins could have therapeutic benefits for treating demyelinating CMT...
Discovery of aminoquinolines as a new class of potent inhibitors of heat shock protein 90 (Hsp90): Synthesis, biology, and molecular modelingThota Ganesh
Chemical Biology Discovery Center, 1510 Clifton Road, Emory University, Atlanta, GA 30322, USA
Bioorg Med Chem 16:6903-10. 2008..These compounds represent a new class of Hsp90 inhibitors with simple chemical structures...
Nitric oxide-dependent proteasomal degradation of cytochrome P450 2B proteinsChoon Myung Lee
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
J Biol Chem 283:889-98. 2008..These data are consistent with the hypothesis that NO-dependent CYP2B ubiquitination and proteasomal degradation are dependent on protein modification by reactive nitrogen species...
Hrs interacts with SNAP-25 and regulates Ca(2+)-dependent exocytosisJ Kwong
Department of Pharmacology, Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
J Cell Sci 113:2273-84. 2000..Moreover, overexpression of Hrs in PC12 cells inhibits Ca(2+)-dependent exocytosis. These results suggest that Hrs is involved in regulation of neurosecretion through interaction with SNAP-25...
Ubiquitin C-terminal hydrolase l1 in tumorigenesisJennifer Hurst-Kennedy
Department of Pharmacology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA
Biochem Res Int 2012:123706. 2012..In this paper, we provide an overview of the evidence supporting the involvement of UCH-L1 in tumor development and discuss the potential mechanisms of action of UCH-L1 in oncogenesis...
Huntingtin-associated protein 1 interacts with hepatocyte growth factor-regulated tyrosine kinase substrate and functions in endosomal traffickingYankun Li
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322 3090, USA
J Biol Chem 277:28212-21. 2002..These findings implicate, for the first time, the involvement of HAP1 in the regulation of vesicular trafficking from early endosomes to the late endocytic compartments...
Regulation of synaptophysin degradation by mammalian homologues of seven in absentiaTiffany C Wheeler
Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA
J Biol Chem 277:10273-82. 2002..Our findings indicate that Siah proteins function as E3 ubiquitin-protein ligases to regulate the ubiquitination and degradation of synaptophysin...
Research Grants
- Characterization of a neuronal ubiquitination machineryLian Li; Fiscal Year: 2007..abstract_text> ..
- Mechanisms of Endosome-to-Lysosome Trafficking in BrainLian Li; Fiscal Year: 2007..abstract_text> ..
- Ubiquitin-mediated proteolysis at synaptic terminalsLian Li; Fiscal Year: 2007..These studies should advance our understanding of protein degradation at synaptic terminals, and provide a basis for the development of therapeutic strategies for treating malfunctions of the nervous system. ..
- Pathogenic Mechanisms of Environmental Toxicants in Parkinson's DiseaseLian Li; Fiscal Year: 2010..The results of the proposed studies will promote the discovery of new therapies for preventing and treating this devastating illness. ..
- The PINK1 Mitochondrial Signaling PathwayLian Li; Fiscal Year: 2010..The results of the proposed studies will provide fundamental information needed for the development of effective therapeutics to treat numerous mitochondrial diseases in human. ..
- NOVEL PROTEINS IN NEUROTRANSMITTER RELEASELian Li; Fiscal Year: 2001....
- MOLECULAR GENETIC ANALYSIS OF SYNAPTIC TRANSMISSIONLian Li; Fiscal Year: 2002....
- The PINK1 Mitochondrial Signaling PathwayLian Li; Fiscal Year: 2009..The results of the proposed studies will provide fundamental information needed for the development of effective therapeutics to treat numerous mitochondrial diseases in human. ..
