Noriaki Shimizu

Last Updated :2021/03/02

Affiliations, Positions
Graduate School of Integrated Sciences for Life, Professor
Other Contact Details
TEL : (+81)82-424-6528 FAX : (+81)82-424-0759
My major interst is the genomic and chromosomal plasticity in a broad sense. More specifically, my research focuses on the extrachromosomal genetic element of genomic origin, and the gene amplification that was mediated by the above elements. Such research has implifcations on basic chromosome biology and cancer biology, and it might be applied to the inductrial recombinant protein production.

Basic Information

Major Professional Backgrounds

  • 1994/04/01, 1995/09/30, The Salk Institute for Biological Studies, Visiting Scientist
  • 1983/04/01, 1988/11/30, Yamanouchi Pharmaceutical Co. Ltd., Central Research Laboratories, Researcher
  • 1988/12, Faculty of Integrated Arts and Sciences, Assistant Professor
  • 1992/04, Faculty of INtegrated Arts and Sciences, Hiroshima University, Associate Professor
  • 2006/04, Graduate School of Biosphere Science, Hiroshima University, Associate Professor
  • 2007/04, Graduate School of Biosphere Science, Associate Professor
  • 2008/02, 2019/03/31, Graduate School of Biosphere Science, Professor

Educational Backgrounds

  • Kyoto University, Graduate School, Division of Natural Science, Japan, 1980/04, 1983/03
  • Kyoto University, Faculty of Agriculture, Japan, 1974/04, 1978/03

Academic Degrees

  • Master of Science, Kyoto University
  • Doctor of Science, Kyoto University

Research Fields

  • Agricultural sciences;Boundary agriculture;Applied molecular and cellular biology
  • Biology;Basic biology;Genetics / Chromosome dynamics
  • Biology;Biological Science;Cell biology

Research Keywords

  • Extrachromosomal Element
  • micronuclei
  • Gene Amplification
  • Tumour
  • recombinant protein production

Affiliated Academic Societies

  • The Molecular Biology Society of Japan, 1990
  • The Japanese Biochemical Society, 1989
  • Japanese Cancer Association, 2003
  • Japanese Association for Animal Cell Technology, 2009
  • The Society for Biotechnology, Japan, 2015

Educational Activity

Course in Charge

  1. 2020, Liberal Arts Education Program1, 4Term, Biological production and natural environment
  2. 2020, Liberal Arts Education Program1, 1Term, Experimental Methods and Laboratory Work in Chemistry I
  3. 2020, Liberal Arts Education Program1, 3Term, Experimental Methods and Laboratory Work in Chemistry I
  4. 2020, Liberal Arts Education Program1, 2Term, Experimental Methods and Laboratory Work in Chemistry II
  5. 2020, Liberal Arts Education Program1, 4Term, Experimental Methods and Laboratory Work in Chemistry II
  6. 2020, Undergraduate Education, 4Term, Introduction to Applied Biological Science II
  7. 2020, Undergraduate Education, 1Term, Mammalian Molecular Biology
  8. 2020, Undergraduate Education, Intensive, Laboratory Work in Biological Chemistry
  9. 2020, Undergraduate Education, Academic Year, Graduation Thesis
  10. 2020, Graduate Education (Master's Program) , 3Term, General molecular genetics
  11. 2020, Graduate Education (Master's Program) , 4Term, Practical molecular genetics
  12. 2020, Graduate Education (Master's Program) , 4Term, Applied Molecular Cell Biology II

Research Activities

Academic Papers

  1. ★, Repeat induces not only gene silencing, but also gene activation in mammalian cells, PLOS ONE, 15(6), 20200624
  2. ★, Double-strand breakage in the extrachromosomal double minutes triggers their aggregation in the nucleus, micronucleation, and morphological transformation, GENES CHROMOSOMES & CANCER, 59(3), 133-143, 202003
  3. ★, Targeted amplification of a sequence of interest in artificial chromosome in mammalian cells, Nucleic Acids Research, 47(11), 5998-6006, 20190620
  4. An efficient protein production system via gene amplification on a human artificial chromosome and the chromosome transfer to CHO cells, SCIENTIFIC REPORTS, 9, 20191118
  5. ★, Generation and maintenance of acentric stable double minutes from chromosome arms in inter-species hybrid cells, BMC MOLECULAR AND CELL BIOLOGY, 20, 20190320
  6. Phosphorylated SIRT1 associates with replication origins to prevent excess replication initiation and preserve genomic stability., Nucleic Acids Research, 45(13), 7807-7824, 20170727
  7. ★, Amplification of a transgene within a long array of replication origins favors higher gene expression in animal cells., PLoS ONE, 12(4), e0175585, 20170412
  8. ★, Epigenetic Repeat-Induced Gene Silencing in the Chromosomal and Extrachromosomal Contexts in Human Cells., PLoS ONE, 11(8), e0161288, 20160815
  9. ★, Cloning and characterization of a human genomic sequence that alleviate the repeat-induced gene silencing, PLOS ONE, 11(4), e0153338, 20160414
  10. ★, How a Replication Origin and Matrix Attachment Region Accelerate Gene Amplification under Replication Stress in Mammalian Cells, PLOS ONE, 9(7), e103439, 20140725
  11. ★, Dissection of the Beta-Globin Replication-Initiation Region Reveals Specific Requirements for Replicator Elements during Gene Amplification, PLOS ONE, 8(10), e77350, 20131004
  12. ★, Fusion of the Dhfr/Mtx and IR/MAR Gene Amplification Methods Produces a Rapid and Efficient Method for Stable Recombinant Protein Production, PLOS ONE, 7(12), e52990, 20121231
  13. ★, DNA replication occurs in all lamina positive micronuclei, but never in lamina negative micronuclei, MUTAGENESIS, 27(3), 323-327, 20120512
  14. ★, Efficient Recombinant Production in Mammalian Cells Using a Novel IR/MAR Gene Amplification Method, PLOS ONE, 7(7), e41787, 20120723
  15. High levels of human recombinant cyclooxygenase-1 expression in mammalian cells using a novel gene amplification method, PROTEIN EXPRESSION AND PURIFICATION, 80(1), 41-46, 20111111
  16. ★, Generation of Micronuclei during Interphase by Coupling between Cytoplasmic Membrane Blebbing and Nuclear Budding, PLOS ONE, 6(11), e27233, 20111102
  17. ★, Amplification of a plasmid bearing a mammalian replication initiation region in chromosomal and extrachromosomal contexts, Nucleic Acids Research, 39(3), 958-969, 20110211
  18. Molecular mechanisms of the origin of micronuclei from extrachromosomal elements, MUTAGENESIS, 26(1), 119-123, 20110111
  19. ★, Emergence of Micronuclei and Their Effects on the Fate of Cells under Replication Stress, PLOS ONE, 5(4), e10089, 20100408
  20. Age-dependent increase in lysosome-associated membrane protein 1 and early-onset behavioral deficits in APPSL transgenic mouse model of Alzheimer's disease, NEUROSCIENCE LETTERS, 469(2), 273-277, 20100122
  21. ★, How transcription proceeds in a large artificial heterochromatin in human cells, Nucleic Acids Research, 37(2), 393-404, 20090209
  22. ★, Episomal High Copy Number Maintenance of Hairpin-capped DNA Bearing a Replication Initiation Region in Human Cells, The Journal of Biological Chemistry, 284(36), 24320-24327, 20090904
  23. Extrachromosomal Double Minutes and Chromosomal Homogeneously Staining Regions as Probes for Chromosome Research, CYTOGENETIC AND GENOME RESEARCH, 124, 312-326, 2009
  24. ★, Micronuclei bearing acentric extrachromosomal chromatin are transcriptionally competent and may perturb the cancer cell phenotype., Molecular Cancer Research, 5(7), 695-704, 20070702
  25. ★, Nonselective DNA damage induced by a replication inhibitor results in the selective elimination of extrachromosomal double minutes from human cancer cells, Genes Chromosomes & Cancer, 46(10), 865-874, 200701
  26. ★, Dissection of mammalian replicators by a novel plasmid stability assay, Journal of Cellular Biochemistry, 101(3), 552-565, 2007
  27. Regulation of c-myc through intranuclear localization of its RNA subspecies., Biochemical and Biophysical Reseach Communications, 358(3), 806-810, 20070706
  28. ★, Interconversion of Intra- and Extra-chromosomal Sites of Gene Amplification by Modulation of Gene Expression and DNA Methylation., Journal of Cellular Biochemistry, 102, 515-529, 20070327
  29. Suppression of replication fork progression in low-dose-specic p53-dependent S-phase DNA damage checkpoint, Oncogene, 25(44), 5921-5932, 20060928
  30. A hyper-dynamic equilibrium between promoter-bound and nucleoplasmic dimers controls NF-kB-dependent gene activity., The EMBO Journal, 25, 798-810, 20060222
  31. ★, When, where and how the bridge breaks: anaphase bridge breakage plays a crucial role in gene amplification and HSR generation, Experimental Cell Research, 302(2), 233-243, 20050115
  32. ★, Tracking of microinjected DNA in live cells reveals the intracellular behavior and elimination of extrachromosomal genetic material., Nucleic Acids Research, 33(19), 6296-6307, 20051101
  33. Mechanism of Gene Amplification Mediated by an Extrachromosomal Circular Molecule having a Mammalian Replication Initiation Region., International Journal of Molecular Medicine, 14(4), S18-S18, 20040401
  34. ★, Macroscopic folding and replication of the homogeneously staining region in late S phase leads to the appearance of replication bands in mitotic chromosome, Journal of Cell Science, 117(22), 5303-5312, 20041101
  35. ★, Amplification of plasmids containing a mammalian replication initiation region is mediated by controllable conflict between replication and transcription, Cancer Research, 63(17), 5281-5290, 20030901
  36. ★, Plasmids with a mammalian replication origin and a matrix attachment region initiate the event similar to gene amplification, Cancer Research, 61(19), 6987-6990, 20011001
  37. ★, Replication timing of amplified genetic regions relates to intranuclear localization but not to genetic activity or G/R band, Experimental Cell Research, 268(2), 201-210, 20010815
  38. ★, Selective elimination of acentric double minutes from cancer cells through the extrusion of micronuclei, Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis, 448(1), 81-90, 20000314
  39. ★, Induced detachment of acentric chromatin from mitotic chromosomes lead to their Cytoplasmic localization at G1 and the micronucleation by lamin rearganization at S- phase, Journal of Cell Science, 111, 3275-3285, 20000401
  40. ★, DNA replication-dependent Intranuclear Relocation of Double Minute Chromatin, Journal of Cell Science, 11, 3275-3285, 19980401
  41. Survival by Mac-l-Mediated abherence and Anoikis in Phorbal Ester-treated HL-60 cells, The Journal of Biological Chemistry, 273(25), 15345-15351, 19980401
  42. ★, Selective Entrapment of Extrachromosomally Amplified DNA by Nuclear Budding and Micronucleation during S-phase, The Journal of Cell Biology, 140, 1307-1320, 19980401
  43. Involvement of Mac-l-Mediated Adherence and Sphingosine-l-Phosphate in Survival of Phorbol Ester-treated U937 cells, Biochemical and Biophysical Research Communications, 244(3), 745-750, 19980401
  44. ★, Selective capture of acentric fragments by micronuclei provides a rapid method for purifying extrachromosomally amplified DNA, Nature genetics, 12(1), 65-71, 19960401
  45. ★, Loss of Amplified c-myc Genes in the Spontaneously Differentiated HL-60 Cells, Cancer Research, 54, 3561-3567, 19940401
  46. A Gene Coding for a Zinc Finger Protein is Induced during 12-0-Tetradecanoylphorbol-13-acetate-stimulated HL-60 Cell Differentiation, J. Biochem., 111, 272-277, 19920401
  47. Determination of Transcriptional Activities of Typical Gene Promoters in HL-60 Cells, J. Biochem., 111, 103-108, 19920401
  48. Expression of a Novel Immediate Early Gene during 12-0-Tetradecanoylphorbol-13-acetate-induced Macrophagic Differentiation of HL-60 Cells, J. Biol. Chem., 266, 12157-12161, 19910401
  49. Molecular Cloning and Expression in Escherichia coli of the cDNA Coding for Rat Lipocortin I (Calpactin II), Gene, 65, 141-147, 19880401
  50. 2',5'-Oligoadenylate Synthetase Activity in Lymphocytes from Normal Mouse, J. Biol. Chem., 254, 12034-12037, 19790401

Publications such as books

  1. 2013/04, Brenner's Encyclopedia of Genetics, 2nd edition, Elsevier, 2013, 4, Others

Invited Lecture, Oral Presentation, Poster Presentation

  1. Recombinant protein production in CHO cells using the IR/MAR-amplification based technology, Noriaki Shimizu, Yoshio Araki, Chiemi Noguchi and Tetsuro Hamafuji, The 25th Annual and International Meeting of the Japanese Association for Animal Cell Technology (JAACT 2012), 2012/11/30, Without Invitation, English, Japanese Association for Animal Cell Technology, Nagoya
  2. Application of the Novel and Convenient IR/MAR Gene Amplification Technology to the Production of Recombinant Protein Pharmaceuticals 22nd ESACT (European Society for Animal Cell Technology) meeting at Vienna, Austria, Yoshio Araki, Chiemi Noguchi, Noriaki Shimizu, Tetsuro Hamafuji, Hiroshi Nose and Daisuke Miki, 22nd ESACT (European Society for Animal Cell Technology) meeting, 2011/11, Without Invitation, English, ESACT (European Society for Animal Cell Technology)
  3. Novel, Convenient and Efficient "IR/MAR Gene Amplification Method" for the Production of Recombinant Protein in Animal Cells, Noriaki Shimizu, 10th PEACe (Protein Expression in Animal Cell) conference, 2011/09/25, With Invitation, English, Cascais, Portugal
  4. Gene Amplification in Chromosomal and Extrachromosomal Context, Noriaki Shimizu, The 57th NIBB conference, "Dynamic Genome", 2010/10/15, With Invitation, English, National Institute of Basic Biology (NIBB)
  5. The palindrome at the extrachromosomal and the intrachromosomal context in mammalian cells., Noriaki Shimizu, FASEB Summer Research Conference, 2010/07/10, With Invitation, English, Federation of American Society of Experimental Biology (FASEB), Steamboat, Colorado

Social Activities

History as Peer Reviews of Academic Papers

  1. 2015, Cellular & Molecular Biology Letters, Others, Reviewer, 1
  2. 2014, BMC Biotechnology, Others, Reviewer, 1
  3. 2014, Journal of Molecular Biology, Others, Reviewer, 1
  4. 2013, Science, Others, Reviewer, 1
  5. 2011, Human Molecular Genetics, Others, Reviewer, 1
  6. 2011, Nucleic Acids Research, Others, Reviewer, 1
  7. 2009, Experimental Cell Research, Others, Reviewer, 1
  8. 2006, Oncogene, Others, Reviewer, 1
  9. 2002, Cancer Research, Others, Reviewer, 1
  10. 2015, Mutation Research, Others, Reviewer, 1
  11. 2015, PlosONE, Others, Reviewer, 1