Yue Ming Li

Summary

Affiliation: Memorial Sloan-Kettering Cancer Center
Country: USA

Publications

  1. pmc An exo-cell assay for examining real-time gamma-secretase activity and inhibition
    Christopher C Shelton
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Mol Neurodegener 4:22. 2009
  2. pmc Soluble oligomers of the intramembrane serine protease YqgP are catalytically active in the absence of detergents
    Xiaojun Lei
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Biochemistry 47:11920-9. 2008
  3. ncbi request reprint Stereoselective synthesis of photoreactive peptidomimetic gamma-secretase inhibitors
    Jiong Chun
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Org Chem 69:7344-7. 2004
  4. pmc Structure of gamma-secretase and its trimeric pre-activation intermediate by single-particle electron microscopy
    Fabiana Renzi
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 286:21440-9. 2011
  5. pmc BMS-708,163 targets presenilin and lacks notch-sparing activity
    Christina J Crump
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States
    Biochemistry 51:7209-11. 2012
  6. pmc Activation and intrinsic gamma-secretase activity of presenilin 1
    Kwangwook Ahn
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065
    Proc Natl Acad Sci U S A 107:21435-40. 2010
  7. ncbi request reprint Presenilins and gamma-secretase inhibitors affect intracellular trafficking and cell surface localization of the gamma-secretase complex components
    Hong Wang
    The Fisher Center for Alzheimer s Disease Research and the Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York 10021, USA
    J Biol Chem 279:40560-6. 2004
  8. pmc Modulation of gamma-secretase specificity using small molecule allosteric inhibitors
    Christopher C Shelton
    Molecular Pharmacology and Chemistry Program and High Throughput Screening Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 106:20228-33. 2009
  9. ncbi request reprint The synthesis and preliminary biological evaluation of a novel steroid with neurotrophic activity: NGA0187
    Zihao Hua
    Laboratory for Bioorganic Chemistry, Sloan Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10021, USA
    J Org Chem 70:9849-56. 2005
  10. doi request reprint An APP inhibitory domain containing the Flemish mutation residue modulates gamma-secretase activity for Abeta production
    Yuan Tian
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    Nat Struct Mol Biol 17:151-8. 2010

Research Grants

  1. Regulation and function of gamma-secretase
    Yueming Li; Fiscal Year: 2007
  2. Regulation and function of gamma-secretase
    Yueming Li; Fiscal Year: 2009

Collaborators

Detail Information

Publications29

  1. pmc An exo-cell assay for examining real-time gamma-secretase activity and inhibition
    Christopher C Shelton
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Mol Neurodegener 4:22. 2009
    ....
  2. pmc Soluble oligomers of the intramembrane serine protease YqgP are catalytically active in the absence of detergents
    Xiaojun Lei
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Biochemistry 47:11920-9. 2008
    ..Therefore, this work not only provides a unique system for elucidating the reaction mechanism of rhomboid but also will facilitate the characterization of other intramembrane proteases as well as non-protease membrane proteins...
  3. ncbi request reprint Stereoselective synthesis of photoreactive peptidomimetic gamma-secretase inhibitors
    Jiong Chun
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Org Chem 69:7344-7. 2004
    ..Two routes leading from 19 to compounds 2 and 3 are evaluated. The application of 3 as an activity-based probe has been demonstrated by localizing gamma-secretase activity in the plasma membrane of intact cells...
  4. pmc Structure of gamma-secretase and its trimeric pre-activation intermediate by single-particle electron microscopy
    Fabiana Renzi
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 286:21440-9. 2011
    ..Comparison with the structure of a trimeric pre-activation intermediate suggested that the incorporation of PEN-2 might contribute to the maturation of the active site architecture...
  5. pmc BMS-708,163 targets presenilin and lacks notch-sparing activity
    Christina J Crump
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States
    Biochemistry 51:7209-11. 2012
    ..Furthermore, BMS-708,163 blocks the binding of four different active site-directed GSI photoaffinity probes. We therefore report that this compound acts as a nonselective γ-secretase inhibitor...
  6. pmc Activation and intrinsic gamma-secretase activity of presenilin 1
    Kwangwook Ahn
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065
    Proc Natl Acad Sci U S A 107:21435-40. 2010
    ..Thus, we conclusively establish that activated PS is catalytically competent and the bimolecular interaction of PS1 and PEN2 can convert the PS1 zymogen to an active protease...
  7. ncbi request reprint Presenilins and gamma-secretase inhibitors affect intracellular trafficking and cell surface localization of the gamma-secretase complex components
    Hong Wang
    The Fisher Center for Alzheimer s Disease Research and the Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York 10021, USA
    J Biol Chem 279:40560-6. 2004
    ....
  8. pmc Modulation of gamma-secretase specificity using small molecule allosteric inhibitors
    Christopher C Shelton
    Molecular Pharmacology and Chemistry Program and High Throughput Screening Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 106:20228-33. 2009
    ..Furthermore, this class of selective inhibitors provides the basis for development of Alzheimer disease therapeutic agents...
  9. ncbi request reprint The synthesis and preliminary biological evaluation of a novel steroid with neurotrophic activity: NGA0187
    Zihao Hua
    Laboratory for Bioorganic Chemistry, Sloan Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10021, USA
    J Org Chem 70:9849-56. 2005
    ..A preliminary evaluation of its ability to stimulate the neurite outgrowth was also evaluated with PC12 cell...
  10. doi request reprint An APP inhibitory domain containing the Flemish mutation residue modulates gamma-secretase activity for Abeta production
    Yuan Tian
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    Nat Struct Mol Biol 17:151-8. 2010
    ....
  11. pmc Dual role of alpha-secretase cleavage in the regulation of gamma-secretase activity for amyloid production
    Yuan Tian
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    J Biol Chem 285:32549-56. 2010
    ..This work reveals an unforeseen role for α-secretase in generating an endogenous γ-secretase inhibitor that down-regulates the production of Aβ. Deregulation of this feedback mechanism may contribute to the pathogenesis of AD...
  12. pmc Processing of Notch and amyloid precursor protein by gamma-secretase is spatially distinct
    Leonid Tarassishin
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 101:17050-5. 2004
    ..Furthermore, the fact that inhibitors first target gamma-secretase in the plasma membrane for Notch processing, and not for APP, will have important implications for drug development to treat Alzheimer's disease and cancer...
  13. pmc Familial Alzheimer disease presenilin-1 mutations alter the active site conformation of γ-secretase
    De Ming Chau
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    J Biol Chem 287:17288-96. 2012
    ....
  14. pmc Stereo-controlled synthesis of novel photoreactive gamma-secretase inhibitors
    Guangli Yang
    Organic Synthesis Core Facility, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
    Bioorg Med Chem Lett 19:922-5. 2009
    ..Compounds 2 and 3 are potent gamma-secretase inhibitors and directly interact with presenilin-1, a catalytic subunit of gamma-secretase...
  15. ncbi request reprint Total synthesis as a resource in drug discovery: the first in vivo evaluation of panaxytriol and its derivatives
    Heedong Yun
    Department of Chemistry, Columbia University, 3000 Broadway, New York, New York, 10027, USA
    J Org Chem 70:10375-80. 2005
    ..Finally, preliminary in vitro evaluation of panaxytriol indicates that it possesses neurotrophic activity...
  16. pmc A miniaturized 1536-well format gamma-secretase assay
    Christopher C Shelton
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Assay Drug Dev Technol 7:461-70. 2009
    ..This validated assay can readily be used for primary screening against large chemical libraries searching for novel inhibitors of gamma-secretase activity that may represent potential therapeutics for AD and a variety of neoplasms...
  17. pmc A novel high throughput 1536-well Notch1 γ -secretase AlphaLISA assay
    De Ming Chau
    Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA
    Comb Chem High Throughput Screen 16:415-24. 2013
    ....
  18. pmc Development of clickable active site-directed photoaffinity probes for γ-secretase
    Christina J Crump
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Bioorg Med Chem Lett 22:2997-3000. 2012
    ....
  19. pmc Characterization of an atypical gamma-secretase complex from hematopoietic origin
    Lisa Placanica
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Biochemistry 49:2796-804. 2010
    ..These data underscore the need for studying endogenous gamma-secretase to fully understand of the biology of gamma-secretase and its complexity as a molecular target for the development of disease therapeutics...
  20. ncbi request reprint Total synthesis of (+/-)-jiadifenin and studies directed to understanding its SAR: probing mechanistic and stereochemical issues in palladium-mediated allylation of enolate-like structures
    David A Carcache
    Laboratory for Bioorganic Chemistry, Sloan Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10021, USA
    J Am Chem Soc 128:1016-22. 2006
    ..While in the particular case at hand, we find very little difference in stereochemical outcome as one partitions between the inter- and intramolecular pathways, the techniques employed are applicable to other systems...
  21. pmc High-throughput identification of inhibitors of human mitochondrial peptide deformylase
    Christophe Antczak
    High Throughput Screening Core Facility, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Biomol Screen 12:521-35. 2007
    ....
  22. doi request reprint The processing of human rhomboid intramembrane serine protease RHBDL2 is required for its proteolytic activity
    Xiaojun Lei
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    J Mol Biol 394:815-25. 2009
    ....
  23. pmc Pen2 and presenilin-1 modulate the dynamic equilibrium of presenilin-1 and presenilin-2 gamma-secretase complexes
    Lisa Placanica
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    J Biol Chem 284:2967-77. 2009
    ....
  24. pmc A dimeric Smac/diablo peptide directly relieves caspase-3 inhibition by XIAP. Dynamic and cooperative regulation of XIAP by Smac/Diablo
    Zhonghua Gao
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Biol Chem 282:30718-27. 2007
    ..We also show that XIAP homotrimerizes via its C-terminal Ring domain, making its inhibitory activity toward caspase-3 more susceptible to Smac...
  25. pmc Development and mechanism of γ-secretase modulators for Alzheimer's disease
    Christina J Crump
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, United States
    Biochemistry 52:3197-216. 2013
    ..Various models are proposed and discussed. Despite the progress of GSM research, many outstanding issues remain to be investigated to achieve the ultimate goal of developing GSMs as effective AD therapies. ..
  26. ncbi request reprint {gamma}-Secretase Substrate Concentration Modulates the Abeta42/Abeta40 Ratio: IMPLICATIONS FOR ALZHEIMER DISEASE
    Ye Ingrid Yin
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021 and Department of Biology, Rensselaer Polytechnic Institute, Troy, New York 12180
    J Biol Chem 282:23639-44. 2007
    ..Therefore, strategies lowering the Abeta42/Abeta40 ratio through partial reduction of gamma-secretase substrate production may introduce a practical therapeutic modality for treatment of AD...
  27. ncbi request reprint Total synthesis of (-)-scabronine G, an inducer of neurotrophic factor production
    Stephen P Waters
    Laboratory for Bioorganic Chemistry and Laboratory of Biochemistry and Pharmacology, Sloan Kettering Institute for Cancer Research, New York, New York 10021, USA
    J Am Chem Soc 127:13514-5. 2005
    ..Scabronine G and its more potent methyl ester (also prepared) display activity as nonpeptidyl inducers of nerve growth factor production...
  28. pmc gamma-Secretase inhibitors abrogate oxaliplatin-induced activation of the Notch-1 signaling pathway in colon cancer cells resulting in enhanced chemosensitivity
    Raymond D Meng
    Department of Medicine, Division of Solid Tumor Oncology, Laboratory of New Drug Development, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Cancer Res 69:573-82. 2009
    ..Therefore, combining GSIs with chemotherapy may represent a novel approach for treating metastatic colon cancers by mitigating the development of chemoresistance...
  29. pmc Gender- and age-dependent gamma-secretase activity in mouse brain and its implication in sporadic Alzheimer disease
    Lisa Placanica
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America
    PLoS ONE 4:e5088. 2009
    ..In addition, deceased Notch gamma-secretase activity may also contribute to neurodegeneration. Therefore, this study implicates altered gamma-secretase activity and specificity as a possible mechanism of sporadic AD during aging...

Research Grants5

  1. Regulation and function of gamma-secretase
    Yueming Li; Fiscal Year: 2007
    ..Moreover, these investigations will facilitate the development of potent and specific inhibitors of gamma-secretase for potential AD therapies. ..
  2. Regulation and function of gamma-secretase
    Yueming Li; Fiscal Year: 2009
    ..Moreover, these investigations will facilitate the development of potent and specific inhibitors of gamma-secretase for potential AD therapies. ..