Junmin Peng

Summary

Affiliation: Emory University
Country: USA

Publications

  1. pmc Identification and validation of eukaryotic aspartate and glutamate methylation in proteins
    Robert Sprung
    Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390 9038, USA
    J Proteome Res 7:1001-6. 2008
  2. ncbi request reprint Evaluation of proteomic strategies for analyzing ubiquitinated proteins
    Junmin Peng
    Department of Human Genetics, Center for Neurodegenerative Disease, School of Medicine, Emory University, Atlanta, GA 30322, USA
    BMB Rep 41:177-83. 2008
  3. ncbi request reprint Semiquantitative proteomic analysis of rat forebrain postsynaptic density fractions by mass spectrometry
    Junmin Peng
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    J Biol Chem 279:21003-11. 2004
  4. 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
  5. 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
  6. 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
  7. pmc Nuclear Akt associates with PKC-phosphorylated Ebp1, preventing DNA fragmentation by inhibition of caspase-activated DNase
    Jee Yin Ahn
    Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
    EMBO J 25:2083-95. 2006
  8. 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
  9. 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
  10. pmc Proteomic identification of novel proteins associated with Lewy bodies
    Qiangwei Xia
    Department of Human Genetics, The Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Front Biosci 13:3850-6. 2008

Research Grants

  1. Regulation of Ubiquitin Chain Topology
    Junmin Peng; Fiscal Year: 2005
  2. Quantitative approach to postsynaptic density proteome
    Junmin Peng; Fiscal Year: 2006
  3. A proteomics approach to ubiquitination
    Junmin Peng; Fiscal Year: 2007

Collaborators

Detail Information

Publications48

  1. pmc Identification and validation of eukaryotic aspartate and glutamate methylation in proteins
    Robert Sprung
    Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390 9038, USA
    J Proteome Res 7:1001-6. 2008
    ..The substrate proteins identified here provide a stepping stone for future biochemical characterization of protein methylation pathways...
  2. ncbi request reprint Evaluation of proteomic strategies for analyzing ubiquitinated proteins
    Junmin Peng
    Department of Human Genetics, Center for Neurodegenerative Disease, School of Medicine, Emory University, Atlanta, GA 30322, USA
    BMB Rep 41:177-83. 2008
    ..Here I review the advances and caveats of these strategies, emphasizing caution in the validation of ubiquitinated proteins and in the interpretation of raw data...
  3. ncbi request reprint Semiquantitative proteomic analysis of rat forebrain postsynaptic density fractions by mass spectrometry
    Junmin Peng
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    J Biol Chem 279:21003-11. 2004
    ..Thus this proteomic study reveals crucial information about molecular abundance as well as molecular diversity in the PSD, and provides a basis for further studies on the molecular mechanisms of synaptic function and plasticity...
  4. 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...
  5. 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...
  6. 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
    ....
  7. pmc Nuclear Akt associates with PKC-phosphorylated Ebp1, preventing DNA fragmentation by inhibition of caspase-activated DNase
    Jee Yin Ahn
    Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
    EMBO J 25:2083-95. 2006
    ..Moreover, knocking down of Akt diminishes the antiapoptotic effect of Ebp1 in the nucleus. Thus, nuclear Akt might contribute to suppressing apoptosis through interaction with Ebp1...
  8. 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...
  9. 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...
  10. pmc Proteomic identification of novel proteins associated with Lewy bodies
    Qiangwei Xia
    Department of Human Genetics, The Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Front Biosci 13:3850-6. 2008
    ....
  11. pmc Stable isotope labeling with amino acids in Drosophila for quantifying proteins and modifications
    Ping Xu
    Department of Human Genetics, Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Proteome Res 11:4403-12. 2012
    ..Together, the data demonstrate the application of the SILAC principle in D. melanogaster, facilitating the integration of powerful fly genomics with emerging proteomics...
  12. 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...
  13. 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...
  14. pmc Phosphoproteomic analysis of human brain by calcium phosphate precipitation and mass spectrometry
    Qiangwei Xia
    Department of Human Genetics, The Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Proteome Res 7:2845-51. 2008
    ..A majority of sites were not described previously. This study demonstrates the feasibility of combining calcium phosphate precipitation with mass spectrometry for phosphoproteome analysis of postmortem human brain tissue...
  15. pmc Proteomics analysis reveals novel components in the detergent-insoluble subproteome in Alzheimer's disease
    Yair M Gozal
    Department of Neurology, Emory University, Atlanta, Georgia 30322, USA
    J Proteome Res 8:5069-79. 2009
    ....
  16. pmc Human BRE1 is an E3 ubiquitin ligase for Ebp1 tumor suppressor
    Zhixue Liu
    Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
    Mol Biol Cell 20:757-68. 2009
    ..It is robustly phosphorylated and localized in the nucleus of primary gliomas, correlating with hBre1 subcellular residency. Thus, hBre1 inhibits Ebp1's tumor suppressive activity through mediating its polyubiquitination and degradation...
  17. 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
    ....
  18. pmc Loss of LR11/SORLA enhances early pathology in a mouse model of amyloidosis: evidence for a proximal role in Alzheimer's disease
    Sara E Dodson
    Center for Neurodegenerative Disease, Emory University, Atlanta, Georgia 30322, USA
    J Neurosci 28:12877-86. 2008
    ..The results of the current study support the hypothesis that control of LR11 expression may exert critical effects on Alzheimer's disease susceptibility in humans...
  19. ncbi request reprint Relative and absolute quantification of postsynaptic density proteome isolated from rat forebrain and cerebellum
    Dongmei Cheng
    Department of Human Genetics, Center for Neurodegenerative Disease, Emory University, Atlanta, Georgia 30322, USA
    Mol Cell Proteomics 5:1158-70. 2006
    ..Overall this study delineates a crucial molecular difference between forebrain and cerebellar PSDs and provides a quantitative framework for measuring the molecular stoichiometry of the PSD...
  20. pmc Proteomic analysis of hippocampal dentate granule cells in frontotemporal lobar degeneration: application of laser capture technology
    Yair M Gozal
    Department of Neurology, School of Medicine, Emory University, Atlanta, GA, USA
    Front Neurol 2:24. 2011
    ..Application of LCM is a valuable tool in the molecular analysis of complex tissues, and its application in the proteomic characterization of neurodegenerative disorders such as FTLD-U may be used to identify proteins altered in disease...
  21. pmc Galectin-3 is a candidate biomarker for amyotrophic lateral sclerosis: discovery by a proteomics approach
    Jian Ying Zhou
    Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Proteome Res 9:5133-41. 2010
    ..The challenge is to validate our biomarker candidate proteins as true biomarkers for ALS that will be useful for diagnosis and/or monitoring disease activity in future clinical trials...
  22. pmc Neuroprotective actions of PIKE-L by inhibition of SET proteolytic degradation by asparagine endopeptidase
    Zhixue Liu
    Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA
    Mol Cell 29:665-78. 2008
    ..Moreover, AEP also mediated stroke-provoked SET cleavage and cell death in brain. Thus, AEP might be one of the proteinases activated by acidosis triggering neuronal injury during neuroexcitotoxicity or ischemia...
  23. pmc Systematical optimization of reverse-phase chromatography for shotgun proteomics
    Ping Xu
    Department of Human Genetics, Center for Neurodegenerative Diseases, Emory University, Atlanta, Georgia 30322, USA
    J Proteome Res 8:3944-50. 2009
    ..After full optimization, 1012 proteins (clustered in 806 groups) with an estimated protein false discovery rate of approximately 3% were identified in 1 microg of yeast lysate in a single 160-min LC-MS/MS run...
  24. pmc Huntingtin-associated protein 1 interacts with Ahi1 to regulate cerebellar and brainstem development in mice
    Guoqing Sheng
    Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA
    J Clin Invest 118:2785-95. 2008
    ..These findings provide insight into the pathogenesis of Joubert syndrome and demonstrate the critical role of the Ahi1-Hap1 complex in early brain development...
  25. pmc Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating intragenic H3K4me2 methylation
    Rui Fang
    Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women s Hospital, 221 Longwood Avenue, Boston, MA 02115, USA
    Mol Cell 39:222-33. 2010
    ..These data provide a possible molecular mechanism linking LSD2 to transcriptional regulation after initiation...
  26. ncbi request reprint Merger of laser capture microdissection and mass spectrometry: a window into the amyloid plaque proteome
    Yair M Gozal
    Department of Human Genetics, Center for Neurodegenerative Diseases, School of Medicine, Emory University, Atlanta, 30322, USA
    Methods Enzymol 412:77-93. 2006
    ..Finally, the data were corroborated by independent experiments using the approach of immunohistochemistry. Taken together, the merger of LCM and MS is a powerful tool to probe the proteome of any given pathological lesions...
  27. 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...
  28. ncbi request reprint A proteomics approach to understanding protein ubiquitination
    Junmin Peng
    Department of Cell Biology, 240 Longwood Avenue, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Biotechnol 21:921-6. 2003
    ..The methodology described here provides a general tool for the large-scale analysis and characterization of protein ubiquitination...
  29. pmc Structural basis of SETD6-mediated regulation of the NF-kB network via methyl-lysine signaling
    Yanqi Chang
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    Nucleic Acids Res 39:6380-9. 2011
    ..Given the restriction of Rubisco to plant species, this particular appearance of the protein lysine methyltransferase has been evolutionarily well conserved...
  30. ncbi request reprint Proteomic characterization of postmortem amyloid plaques isolated by laser capture microdissection
    Lujian Liao
    Department of Human Genetics, Center for Neurodegenerative Disease, Enory University School of Medicine, Atlanta, GA 30322, USA
    J Biol Chem 279:37061-8. 2004
    ..Overall, our results revealed for the first time the sub-proteome of amyloid plaques that is important for further studies on disease biomarker identification and molecular mechanisms of AD pathogenesis...
  31. ncbi request reprint Evaluation of multidimensional chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) for large-scale protein analysis: the yeast proteome
    Junmin Peng
    Department of Cell Biology, and Taplin Biological Mass Spectrometry Facility, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    J Proteome Res 2:43-50. 2003
    ..New criteria are proposed to decrease false-positives to less than 1% and to greatly reduce the need for manual interpretation while permitting more proteins to be identified...
  32. pmc Nuclear accumulation of stress response mRNAs contributes to the neurodegeneration caused by Fragile X premutation rCGG repeats
    Abrar Qurashi
    Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA
    PLoS Genet 7:e1002102. 2011
    ..Together these findings suggest that abnormal nuclear accumulation of these mRNAs, likely as a result of impaired nuclear export, could contribute to FXTAS pathogenesis...
  33. pmc Characterization of polyubiquitin chain structure by middle-down mass spectrometry
    Ping Xu
    Department of Human Genetics, Center for Neurodegenerative Diseases, Emory University, Atlanta, Georgia 30322, USA
    Anal Chem 80:3438-44. 2008
    ..g., forked chains) is also discussed. Together, this middle-down MS strategy provides a novel complementary method for studying the length and linkages of complex polyUb chain structures...
  34. pmc Regulation of estrogen receptor alpha by the SET7 lysine methyltransferase
    Krithika Subramanian
    Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA
    Mol Cell 30:336-47. 2008
    ..These findings raise the possibility that generation, recognition, and removal of modifications within the ER hinge region generate "ER modification cassettes" that yield distinct patterns for signaling downstream events...
  35. pmc Dissecting the ubiquitin pathway by mass spectrometry
    Ping Xu
    Department of Human Genetics, Center for Neurodegenerative Disease, Emory University, Atlanta, GA 30322, USA
    Biochim Biophys Acta 1764:1940-7. 2006
    ....
  36. ncbi request reprint Proteomic analysis of ubiquitin conjugates in yeast
    Junmin Peng
    Department of Human Genetics, Center for Neurodegenerative Diseases, Emory University, Atlanta, Georgia, USA
    Methods Enzymol 399:367-81. 2005
    ..The method provides a generic approach for biochemical characterization of ubiquitinated proteins and can be extended to analyze targets of ubiquitin-like molecules...
  37. pmc SOX4 interacts with plakoglobin in a Wnt3a-dependent manner in prostate cancer cells
    Yu Heng Lai
    Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
    BMC Cell Biol 12:50. 2011
    ..Thus, the identification of additional SOX4 binding partners is essential for elucidating the mechanism of SOX4-mediated effects in cancer progression...
  38. doi request reprint At the crossroads of ubiquitin signaling and mass spectrometry
    Eric Dammer
    Department of Human Genetics, Center for Neurodegenerative Diseases, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA
    Expert Rev Proteomics 7:643-5. 2010
    ..The First Conference on Proteomics of Protein Degradation & Ubiquitin Pathways in Vancouver, Canada, covers the latest progress in key topics of the field and fosters collaborative interactions among researchers...
  39. ncbi request reprint ELMOD2 is an Arl2 GTPase-activating protein that also acts on Arfs
    J Bradford Bowzard
    Department of Biochemistry, Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Biol Chem 282:17568-80. 2007
    ....
  40. ncbi request reprint Neuronal morphogenesis is regulated by the interplay between cyclin-dependent kinase 5 and the ubiquitin ligase mind bomb 1
    Eun Ah Choe
    Department of Human Genetics, Center for Neurodegenerative Diseases, School of Medicine, Emory University, Atlanta, Georgia 30322, USA
    J Neurosci 27:9503-12. 2007
    ..The data strongly support that the negative interplay between Mib1 and p35/CDK5 may integrate the activities of multiple pathways during neuronal development...
  41. doi request reprint Clinical proteomics in neurodegenerative diseases
    Jian Ying Zhou
    Department of Human Genetics, Center for Neurodegenerative Disease, Emory University, Atlanta, GA, USA
    Proteomics Clin Appl 1:1342-50. 2007
    ....
  42. ncbi request reprint Nucleophosmin/B23, a nuclear PI(3,4,5)P(3) receptor, mediates the antiapoptotic actions of NGF by inhibiting CAD
    Jee Yin Ahn
    Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, Georgia 30322, USA
    Mol Cell 18:435-45. 2005
    ..Moreover, B23 mutants that can not associate with PI(3,4,5)P(3) fail to prevent DNA fragmentation. Thus, the nuclear B23-PI(3,4,5)P(3) complex regulates the antiapoptotic activity of NGF in the nucleus...
  43. pmc Prolyl 4-hydroxylation regulates Argonaute 2 stability
    Hank H Qi
    Department of Pathology, Harvard Medical School, New Research Building 854, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
    Nature 455:421-4. 2008
    ..These findings identify hydroxylation as a post-translational modification important for Ago2 stability and effective RNA interference...
  44. ncbi request reprint Automation of nanoscale microcapillary liquid chromatography-tandem mass spectrometry with a vented column
    Lawrence J Licklider
    Taplin Biological Mass Spectrometry Facility, Harvard Medical School, Boston, Massachusetts 02115, USA
    Anal Chem 74:3076-83. 2002
    ..The procedures for constructing and using a V-column require minimal changes in current methods and equipment for nano-LC-MS analyses using columns of 100-microm diameter and smaller...
  45. pmc Proteomics of gliomas: initial biomarker discovery and evolution of technology
    Juliya Kalinina
    Laboratory of Molecular Neuro Oncology, Departments of Neurosurgery, Hematology and Medical Oncology, School of Medicine, and Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA
    Neuro Oncol 13:926-42. 2011
    ....
  46. pmc The deubiquitinating enzyme ataxin-3, a polyglutamine disease protein, edits Lys63 linkages in mixed linkage ubiquitin chains
    Brett J Winborn
    Department of Neurology, University of Michigan, Ann Arbor, Michigan 48108, USA
    J Biol Chem 283:26436-43. 2008
    ..These findings establish ataxin-3 as a novel DUB that edits topologically complex chains...
  47. pmc Lysine propionylation and butyrylation are novel post-translational modifications in histones
    Yue Chen
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Mol Cell Proteomics 6:812-9. 2007
    ....
  48. ncbi request reprint Cdk5-mediated inhibition of the protective effects of transcription factor MEF2 in neurotoxicity-induced apoptosis
    Xiaoming Gong
    The Liver Research Center, Department of Medicine, Rhode Island Hospital, Brown University School of Medicine, Providence, Rhode Island 02903, USA
    Neuron 38:33-46. 2003
    ..Our studies reveal a nuclear pathway by which neurotoxin/Cdk5 induces neuronal apoptosis through inhibiting prosurvival nuclear machinery...

Research Grants3

  1. Regulation of Ubiquitin Chain Topology
    Junmin Peng; Fiscal Year: 2005
    ..Our studies will lead to the development of general proteomic tools for polyUb chain topology and better understanding of the diversity and function of polyUb chains. ..
  2. Quantitative approach to postsynaptic density proteome
    Junmin Peng; Fiscal Year: 2006
    ..This tool will allow quick evaluation of the PSD proteomic changes in various samples ranging from neuronal cell cultures to animal models of neurological disease and drug abuse. ..
  3. A proteomics approach to ubiquitination
    Junmin Peng; Fiscal Year: 2007
    ..Once established, the method will be highly useful for profiling ubiquitinated proteome in mammalian samples including clinical tumor tissues. ..