Updated on 2023/03/10

写真a

 
NIIMI Tomoaki
 
Organization
Graduate School of Bioagricultural Sciences Department of Applied Biosciences Lecturer
Graduate School
Graduate School of Bioagricultural Sciences
Undergraduate School
School of Agricultural Sciences Department of Applied Biosciences
Title
Lecturer
Contact information
メールアドレス

Degree 1

  1. Ph. D. ( 1997.3   Nagoya University ) 

Research Areas 2

  1. Others / Others  / Applied Biochemistry

  2. Others / Others  / Applied Molecular Cell Biology

Current Research Project and SDGs 2

  1. 新奇骨誘導タンパク質NELL1の機能解析

  2. 基底膜蛋白質ラミニンの大量生産系の構築

Research History 6

  1. 名古屋大学大学院生命農学研究科講師

    2016.4

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    Country:Japan

  2. 名古屋大学大学院生命農学研究科助教

    2007.4 - 2015.3

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    Country:Japan

  3. 名古屋大学大学院生命農学研究科助手

    2004.4 - 2007.3

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    Country:Japan

  4. Researcher, Sekiguchi Biomatrix Signaling Project, ERATO, Japan Science and Technology Agency

    2001.3 - 2004.3

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    Country:Japan

  5. Visiting Fellow, National Cancer Institute

    1998.10 - 2001.2

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    Country:Japan

  6. Researcher, Nagoya University BioSciences Center

    1997.4 - 1998.9

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    Country:Japan

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Education 2

  1. Nagoya University   Graduate School, Division of Agriculture   Graduate program for Biochemical Regulation

    - 1997

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    Country: Japan

  2. Nagoya University   Faculty of Agriculture   Department of Food Science

    - 1991

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    Country: Japan

Professional Memberships 3

  1. 日本農芸化学会

  2. The Molecular Biology Society of JAPAN

  3. The Japanese Society for Matrix Biology and Medicine

 

Papers 54

  1. Conformational change of the hairpin-like structured Robo2 ectodomain allows NELL1/2 binding. Reviewed

    1. Miyaguchi, M., Nakanishi, Y., Maturana, A.D., Mizutani, K., and Niimi, T.

    Journal of Molecular Biology   Vol. 434   page: 167777   2022.10

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: DOI: 10.1016/j.jmb.2022.167777.

  2. Roles of Slit Ligands and Their Roundabout (Robo) Family of Receptors in Bone Remodeling. Invited Reviewed

    Advances in Experimental Medicine and Biology   Vol. 21   page: 143 - 154   2021

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    Language:English  

    DOI: 10.1007/5584_2020_586

    PubMed

  3. 骨形成を促進する新奇因子NELL1の骨誘導分子基盤の解明

    新美友章

    Precision Medicine   Vol. 4 ( 9 ) page: 884 - 886   2021.8

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    Authorship:Corresponding author   Language:Japanese  

  4. 骨形成を促進する新奇因子NELL1の骨誘導分子基盤の解明

    新美友章

    メディカル・サイエンス・ダイジェスト   Vol. 47 ( 2 ) page: 106 - 107   2021.2

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    Authorship:Corresponding author   Language:Japanese  

  5. RBM20 Regulates CaV1.2 Surface Expression by Promoting Exon 9*Inclusion of CACNA1C in Neonatal Rat Cardiomyocytes

    Morinaga Akihito, Ito Jumpei, Niimi Tomoaki, Maturana Andres D.

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   Vol. 20 ( 22 )   2019.11

  6. Robo2 contains a cryptic binding site for neural EGFL-like (NELL) protein 1/2. Reviewed

    Yamamoto N, Kashiwagi M, Ishihara M, Kojima T, Maturana AD, Kuroda S, Niimi T

    The Journal of biological chemistry   Vol. 294 ( 12 ) page: 4693 - 4703   2019.3

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1074/jbc.RA118.005819

    Web of Science

    PubMed

  7. Scaffold protein Enigma Homolog activates CREB whereas a short splice variant prevents CREB activation in cardiomyocytes.

    Ito, J., Iijima, M., Yoshimoto, N., Niimi, T., Kuroda, S., Maturana, A. D.

    Cell. Signal.   Vol. 27   page: 2425-2433   2015.12

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  8. Mapping the heparin-binding site of the osteoinductive protein NELL1 by site-directed mutagenesis. Reviewed

    Takahashi, K., Imai, A., Iijima, M., Yoshimoto, N., Maturana, A. D., Kuroda, S., and Niimi, T.

    FEBS Letters   Vol. 589   page: 4026-4032   2015.12

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  9. Intracellular trafficking of bio-nanocapsule-liposome complex: Identification of fusogenic activity in the pre-S1 region of hepatitis B virus surface antigen L protein. Reviewed

    Somiya, M., Sasaki, Y., Matsuzaki, T., Iijima, M., Yoshimoto, N., Niimi, T., Maturana, A. D., and Kuroda, S.

    J. Controll. Release   Vol. 212   page: 10-18   2015.8

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    Language:English   Publishing type:Research paper (scientific journal)  

  10. One-step scalable preparation method for non-cationic liposomes with high siRNA content. Reviewed

    Somiya, M., Yamaguchi, K., Liu, Q., Niimi, T., Maturana, A. D., Iijima, M., Yoshimoto, N., and Kuroda, S.

    Int. J. Pharm.   Vol. 490   page: 316-323   2015.7

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  11. Virosomes of hepatitis B virus envelope L proteins containing doxorubicin: synergistic enhancement of human liver-specific anti-tumor growth activity by radiotherapy. Reviewed

    Liu, Q., Jung, J., Somiya, M., Iijima, M., Yoshimoto, N., Niimi, T., Maturana, A. D., Shin, S. H., Jeong, S.-Y., Choi, E. K., and Kuroda, S.

    Int. J. Nanomedicine   Vol. 10   page: 4159-4172   2015.6

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  12. Oligomerization-induced conformational change in the C-terminal region of Nel-like molecule 1 (NELL1) protein is necessary for the efficient mediation of murine MC3T3-E1 cell adhesion and spreading. Reviewed

    Nakamura, Y., Hasebe, A., Takahashi, K., Iijima, M., Yoshimoto, N., Maturana, A. D., Ting, K., Kuroda, S., and Niimi, T.

    J. Biol. Chem.   Vol. 289   page: 9781-9794   2014.4

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  13. High-throughput de novo screening of receptor agonists with an automated single-cell analysis and isolation system.

    Yoshimoto, N., Tatematsu, K., Iijima, M., Niimi, T., Maturana, A. D., Fujii, I., Kondo, A., Tanizawa, K., and Kuroda, S.

      Vol. 4   page: 4242   2014

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  14. Cell surface-fluorescence immunosorbent assay for real-time detection of hybridomas with efficient antibody secretion at the single-cell level. Anal. Chem. Reviewed

    Kida, A., Iijima, M., Niimi, T., Maturana, A. D., Yoshimoto, N., and Kuroda, S.

    Anal. Chem.   Vol. 85   page: 1753-1759   2013

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  15. Exploring dynamics of molybdate in living animal cells by a genetically encoded FRET nanosensor. Reviewed

    Nakanishi, Y., Iida, S., Ueoka-Nakanishi, H., Niimi, T., Tomioka, R., and Maeshima, M.

    PLoS One.   Vol. 8   page: e58175   2013

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  16. An automated system for high-throughput single cell-based breeding. Reviewed

    Yoshimoto, N., Kida, A., Jie, X., Kurokawa, M., Iijima, M., Niimi, T., Maturana, A. D., Nikaido, I., Ueda, H. R., Tatematsu, K., Tanizawa, K., Kondo, A., Fujii, I., and Kuroda, S.

    Sci. Rep.   Vol. 3   page: 1191   2013

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  17. Nanocapsule-based probe for evaluating the orientation of antibodies immobilized on a solid phase. Reviewed

    Iijima, M., Yoshimoto, N., Niimi, T., Maturana, A. D., and Kuroda, S.

    Analyst.   Vol. 138   page: 3470-3477   2013

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  18. Bio-nanocapsules for signal enhancement of alkaline phosphatase-linked immunosorbent assays. Reviewed

    Iijima, M., Yamamoto, M., Yoshimoto, N., Niimi, T., and Kuroda, S.

    Biosci. Biotechnol. Biochem.   Vol. 77   page: 843-846   2013

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  19. Nano-visualization of oriented-immobilized IgGs on immunosensors by high-speed atomic force microscopy

    Iijima, M., Somiya, M., Yoshimoto, N., Niimi, T., and Kuroda, S. (2012). Nano-visualization of oriented-immobilized IgGs on immunosensors by high-speed atomic force microscopy.

    Sci. Rep.   Vol. 2   page: 790   2012

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  20. NELL-1 promotes cell adhesion and differentiation via Integrin β1 Reviewed

    Shen, J., James, A. W., Chung, J., Lee, K., Zhang, J. B., Ho, S., Lee, K. S., Kim, T. M., Niimi, T., Kuroda, S., Ting, K., and Soo

    J. Cell. Biochem.   Vol. 113   page: 3620-3628   2012

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  21. The C-terminal region of NELL1 mediates osteoblastic cell adhesion through integrin α3β1 Reviewed

    Hasebe, A., Nakamura, Y., Tashima, H., Takahashi, K., Iijima, M., Yoshimoto, N., Ting, K., Kuroda, S., and Niimi, T.

    FEBS Lett.   Vol. 586   page: 2500-2506   2012

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  22. Engineered bio-nanocapsules, hepatitis B virus surface antigen L protein particles, for in vivo active targeting to splenic dendritic cells. Reviewed

    Matsuo, H., Yoshimoto, N., Iijima, M., Niimi, T., Jung, J., Jeon, S.-Y., Choi, E. K., Sewaki, T., Arakawa, T., and Kuroda, S.

    Int. J. Nanomedicine.   Vol. 7   page: 3341-3350   2012

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  23. Targeting of polyplex to human hepatic cells by bio-nanocapsules, hepatitis B virus surface antigen L protein particles Reviewed

    Somiya, M., Yoshimoto, N., Iijima, M., Niimi, T., Dewa, T., Jung, J., and Kuroda, S.

    Bioorg. Med. Chem.   Vol. 20   page: 3873-3879   2012

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  24. Hepatitis B virus envelope L protein-derived bio-nanocapsules: Mechanisms of cellular attachment and entry into human hepatic cells Reviewed

    Yamada, M., Oeda, A., Jung, J. Iijima, M., Yoshimoto, N., Niimi, T., Jeong, S.-Y., Choi, E. K., Tanizawa, K., and Kuroda, S.

    J. Control. Release   Vol. 160   page: 322-329   2012

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  25. Efficient production and characterization of recombinant human NELL1 protein in human embryonic kidney 293-F cells. Reviewed

    Hasebe, A., Tashima, H., Ide, T., Iijima, M., Yoshimoto, N., Ting, K., Kuroda, S., and Niimi, T.

    Mol. Biotechnol.   Vol. 51   page: 58-66   2012

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  26. Nanocapsules incorporating IgG Fc-binding domain derived from Staphylococcus aureus protein A for displaying IgGs on immunosensor chips Reviewed

    Iijima, M., Kadoya, H., Hatahira, S., Hiramatsu, S., Jung, G., Martin, A., Quinn, J., Jung, J., Jeong, S. Y., Choi, E. K., Arakawa, T., Hinako, F., Kusunoki, M., Yoshimoto, N., Niimi, T., Tanizawa, K., and Kuroda, S.

    Biomaterials   Vol. 32   page: 1455-1464   2011

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  27. Fluorophore-labeled nanocapsules displaying IgG Fc-binding domains for the simultaneous detection of multiple antigens. Reviewed

    Iijima, M., Matsuzaki, T., Yoshimoto, N., Niimi, T., Tanizawa, K., and Kuroda, S.

    Biomaterials   Vol. 32   page: 9011-9020   2011

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  28. Efficient and rapid purification of drug- and gene-carrying bio-nanocapsules, hepatitis B virus surface antigen L particles, from Saccharomyces cerevisiae Reviewed

    Jung, J., Iijima, M., Yoshimoto, N., Sasaki, M., Niimi, T., Tatematsu, K., Jeong, S.-Y., Choi, E. K., Tanizawa, K., and Kuroda, S.

    Protein Expr. Purif.   Vol. 78   page: 149-155   2011

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  29. Hepatic stellate cells stimulate HCC cell migration via laminin-5 production Reviewed

    Santamato, A., Fransvea, E., Dituri, F., Caligiuri, A., Quaranta, M., Niimi, T., Pinzani, M., Antonaci, S., and Giannelli, G.

    Clin. Sci.   Vol. 121   page: 159-168   2011

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  30. *The production of recombinant human laminin-332 in a Leishmania tarentolae expression system Reviewed

    Phan, H.P., Sugino, M. and Niimi, T.

    Protein Expr. Purif.   Vol. 68   page: 79-84   2009

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  31. Novel Culture System of Mesenchymal Stromal Cells from Human Subcutaneous Adipose Tissue Reviewed

    Iwashima, S., Ozaki, T., Maruyama, S., Saka, Y., Kobori, M., Omae, K., Yamaguchi, H., Niimi, T., Toriyama, K., Kamei, Y., Torii, S., Murohara, T., Yuzawa, Y., Kitagawa, Y. and Matsuo, S.

    Stem Cells Dev.   Vol. 18   page: 533-543   2009

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  32. Expression of secretoglobin3A2 (SCGB3A2) in primary pulmonary carcinomas Reviewed

    Tachihara-Yoshikawa, M., Ishida, T., Watanabe, K., Sugawara, A., Kanazawa, K., Kanno, R., Suzuki, T., Niimi, T., Kimura, S. and Munakata, M.

    Fukushima J. Med. Sci.   Vol. 54   page: 61-72   2008

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  33. *Expression and chain assembly of human laminin-332 in an insect cell-free translation system Reviewed

    Phan, H.-P., Ezure, T., Ito, M., Kadowaki, T., Kitagawa, Y., and Niimi, T.

    Biosci. Biotechnol. Biochem.   Vol. 72   page: 1847-1852   2008

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  34. Cryptic fragment alpha4 LG4-5 derived from laminin alpha4 chain inhibits de novo adipogenesis by modulating the effect of fibroblast growth factor-2 Reviewed

    Yamashita, H., Goto, C., Tajima, R., Koparal, A. T., Kobori, M., Ohki, K., Shitara, K., Narita, R., Toriyama, K., Torii, S., Niimi, T., and Kitagawa, Y.

    Develop. Growth Differ.   Vol. 50   page: 97-107   2008

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  35. *Transcriptional activation of the human claudin-18 gene promoter through two AP-1 motifs in PMA-stimulated MKN45 gastric cancer cells Reviewed

    Yano, K., Imaeda, T., and Niimi, T.

    Am. J. Physiol. Gastrointest. Liver Physiol.   Vol. 294   page: G336-G343   2008

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  36. The Sp family of transcription factors regulates the human laminin alpha 1 gene in JAR choriocarcinoma cells Reviewed

    Niimi, T., Hayashi, Y., Sekiguchi, K., and Kitagawa, Y.

    Biochim. Biophys. Acta.   Vol. 1759   page: 573-579   2006

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  37. Identification and expression of alternative splice variants of the mouse Ppp1r3b gene in lung epithelial cells Reviewed

    Niimi, T., Kurotani, R., Kimura, S., and Kitagawa, Y.

    Biochem. Biophys. Res. Commun.   Vol. 349   page: 588-596   2006

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  38. Induction of uteroglobin-related protein 2 (Ugrp2) gene expression by the Th2 cytokines IL-4 and IL-13 Reviewed

    Yamada, A., Sheikh, F., Niimi, T., DeMayo, F. J., Keegan, A. D., Donnelly, R. P., Kimura, S.

    J. Immunol.   Vol. 175   page: 5708-5715   2005

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  39. SOX7 and SOX17 regulate the parieetal endoderm-specific enhancer activity of mouse laminin a1 gene Reviewed

    Niimi, T., Hayashi, Y., Futaki, S., and Sekiguchi, K.

    J. Biol. Chem   Vol. 279 ( 36 ) page: 38055-38061   2004

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  40. Identification of an upstream enhancer in the mouse laminin alpha1 gene defining its high level of expression in parietal endoderm cells Reviewed

    Niimi, T. Hayashi, Y., and Sekiguchi, K.

    J. Biol. Chem.   Vol. 14   page: 9332-9338   2003

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  41. A polymorphism in the human UGRP1 gene promoter that regulates transcription is associated with an increased risk of asthma Reviewed

    Niimi, T., Munakata, M., Keck-Waggoner, C. L., Popescu, N. C., Levitt, R. C., Hisada, M., and Kimura, S.

    Am. J. Hum. Genet.   Vol. 70   page: 718-725   2002

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  42. Cloning, expression, and chromosomal localization of the mouse gene (Scgb3a1, alias Ugrp2) that encodes a member of the novel uteroglobin-related protein gene family Reviewed

    Niimi, T., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Srisodsai, A., Zimonjic, D. B., Keck-Waggoner, C. L., Popescu, N. C., and Kimura, S.

    Cytogenet. Genome Res.   Vol. 97   page: 120-127   2002

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  43. claudin-18, a novel downstream target gene for the T/EBP/NKX2.1 homeodomain transcription factor, encodes lung-and stomach-specific isoforms through alternative splicing Reviewed

    Niimi, T., Nagashima, K., Ward, J. M., Minoo, P., Zimonjic, D. B., Popescu, N. C., and Kimura, S.

    Mol. Cell. Biol.   Vol. 21   page: 7380-7390   2001

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  44. UGRP1, a uteroglobin/clara cell secretory protein-related protein, is a novel lung-enriched downstream target gene for the T/EBP?NKX2.1 homeodomain transcription factor Reviewed

    Niimi, T., Keck-Waggoner, C. L., Popescu, N. C., Zhou, Y., Levitt, R. C., and Kimura, S.

    Molecular Endocrinology   Vol. 15   page: 2021-2036   2001

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  45. Differential expression of mRNAs encoding laminin chain variants during in vitro development of mouse blastocysts Reviewed

    Azimi, M., Niimi, T., Yoshida, N., and Kitagawa, Y.

    Cytotechnology   Vol. 31   page: 183-191   1999

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  46. A drosophila gene encoding multiple splice variants of Kazal-type serine protease inhibitor-like proteins with potential destinations of mitochondria, cytosol and the secretory pathway Reviewed

    Niimi, T., Yookoyama, H., Goto, A., Beck, K., and Kitagawa, Y.

    Eur. J. Biochem.   Vol. 266   page: 282-292   1999

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  47. Brachyury (T) expression in embryonal carcinoma P19 cells resembles its expression in primitive streak and tail-bud but not that in notochord Reviewed

    Yamaguchi, H., Niimi, T., Kitagawa, Y., and Miki, K.

    Develop. Growth Differ.   Vol. 41   page: 253-264   1999

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  48. Distinct roles of mouse laminin beta1 long arm domains for alpha1beta1gamma1 trimer formation Reviewed

    Niimi, T. and Kitagawa, Y.

    FEBS Letters   Vol. 400   page: 71-74   1997

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  49. 多様なラミニン分子の形成機構

    新美友章、熊谷知乃、北川泰雄

    生体の科学   Vol. 48   page: 260-267   1997

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  50. Differentiation-dependent expression of laminin-8 (alpha4beta1gamma1) mRNAs in mouse 3T3-L1 adipocytes Reviewed

    Niimi, T., Kumagai, C., Okano, M., and Kitagawa, Y.

    Matrix Biology   Vol. 16   page: 223-230   1997

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  51. Expression of the long arm sequence of mouse laminin alpha1, beta1, or gamma1 chain in COS1 cells and assembly of monkey-mouse hybrid laminin Reviewed

    Niimi, T., Miki, K., and Kitagawa, Y.

    J. Biochem   Vol. 121   page: 854-861   1997

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  52. alpha-へリックス鎖間会合の特異性と互換性-ラミニン異型体の形成機構を中心に-

    北川泰雄、新美友章、熊谷知乃、岡野正樹

    生物物理   Vol. 35   page: 63-69   1995

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  53. Regulated expression of an osteonectin variant in bovine aortic endothelial cells Reviewed

    Jeon, H., Niimi, T., Taniguchi, Y., Miki, K., and Kitagawa, Y.

    Biosci. Biotech. Biochem.   Vol. 58 ( 10 ) page: 1889-1891   1994

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  54. The protective role of polyphenols in cytotoxicity of hydrogen peroxide Reviewed

    Nakayama, T., Niimi, T., Osawa, T., and Kawakishi, S.

    Mutation Research   Vol. 281   page: 77-80   1992

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Books 6

  1. Leishmania tarentolae for the production of multi-subunit complexes, Advances in Experimental Medicine and Biology.

    Niimi, T.( Role: Contributor)

    Springer  2016 

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    Language:English Book type:Scholarly book

  2. Recombinant protein production in the eukaryotic protozoan parasite Leishmania tarentolae: A review. In: Recombinant Gene Expression: Reviews and Protocols, Third Edition, Methods in Molecular Biology.

    Niimi, T.( Role: Sole author)

    Humana Press  2012 

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    Language:English

  3. Expression of multi-subunit proteins in Leishmania tarentolae. In: Recombinant Gene Expression: Reviews and Protocols, Third Edition, Methods in Molecular Biology.

    Sugino, M. and Niimi, T. ( Role: Joint author)

    Humana Press  2012 

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    Language:Japanese

  4. 細胞外マトリックス-基礎と臨床 「基底膜に存在する糖タンパク質」

    熊谷知乃、新美友章、北川泰雄( Role: Joint author)

    愛智出版  2000 

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    Language:Japanese

  5. Extracellular Matrix-Cellular Interaction: Molecules to Diseases"Role of interchain disulfide-bonding in dimer-trimer switch during laminin heterotrimer assembry."

    kitagawa, Y., Niimi, T., and Kumagai, C.( Role: Joint author)

    Japan Sci. Soc. Press, Tokyo/ S. Karger, Basel  1998 

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    Language:English

  6. Animal Cell Technology; Basic & Applied Aspects"Laminin chains expressed in human keratinocytes, mouse 3T3-L1 adipocytes and mouse embryonal carcinoma F9."

    Niimi, T., Kumagai, C., Azimi, M., and Kitagawa, Y.( Role: Joint author)

    Kluwe Academic Publisher, Dordrecht  1997 

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    Language:English

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Presentations 1

  1. 骨分化誘導タンパク質NELL1の新奇受容体候補Robo2の構造特性解析

    宮口昌樹、中西洋一、新美友章

    第44回日本分子生物学会年会  2021.12 

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    Event date: 2021.12

    Language:Japanese   Presentation type:Poster presentation  

    Venue:パシフィコ横浜  

Research Project for Joint Research, Competitive Funding, etc. 1

  1. タイトジャンクション構成蛋白質・クローディン-18a2を指標にした胃癌の新しい分子標的療法の開発

    2006.4 - 2007.3

    上原記念生命科学財団 

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    Grant type:Competitive

KAKENHI (Grants-in-Aid for Scientific Research) 6

  1. 新規シグナル伝達系・NELL-Roboシグナルの骨形成における作用機序の解明

    Grant number:20H02948  2020.4 - 2024.3

    科学研究費助成事業  基盤研究(B)

    新美 友章, 水谷 公彦

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\17550000 ( Direct Cost: \13500000 、 Indirect Cost:\4050000 )

    骨形成を促進する働きのあるタンパク質NELL1とその受容体Robo2が結合する仕組みの解明、NELL1とRobo2の結合により誘導される下流のシグナル伝達経路(NELL-Roboシグナル)の同定を通して、NELL-Roboシグナルが骨組織形成で果たす役割を解明し、NELL1およびRobo2遺伝子やこれらの組換えタンパク質を用いた新奇骨形成因子の創成のための基盤研究を行う。
    乳児期に頭頂骨の骨と骨のつなぎ目が早期に癒合することで知られる頭蓋骨縫合早期癒合症(狭頭症)の原因遺伝子のひとつであるNELL1は、頭蓋顔面の骨格形成に関わる分泌タンパク質をコードしており、その骨形成作用に基づいた骨再生治療への応用が試みられている。しかし、NELL1による骨形成作用の分子基盤、特に細胞表面受容体と下流のシグナル伝達機構は不明な点が多く、臨床応用する際のボトルネックとなっている。本研究では、我々が新たに発見したNELL1 の新奇受容体Roundabout (Robo) 2 と下流のシグナル伝達経路(NELL1-Robo2シグナル)の骨形成における役割を解明することにより、組換えNELL1 タンパク質を利用した骨再生治療の基盤研究を行うことを目的とした。
    昨年度は、Fluorescence resonance energy transfer (FRET) の変化を指標にしたRobo2 の構造解析実験を行い、酸性条件でのFRET測定に適した蛍光タンパク質の選定、およびセンサータンパク質の最適化を経て、酸性条件におけるRobo2の細胞外領域の推定構造を得た。今後、複数の実験系を用いて、この推定構造を確かめる必要があるが、Robo2の新奇受容体としてNELL1が働く分子基盤の一端が解明されたことで本研究成果は重要である。
    京都大学との共同研究であるRobo2細胞外領域の結晶構造解析実験では、タンパク質の大量発現系の構築と精製および結晶化の条件検討を行い、次年度以降に成果が得られることを期待している。
    NELL1の新奇受容体として同定したRobo2は、pH 7付近の生理的条件下においてはNELL1の結合部位がマスクされていて結合できないが、pH 5~6付近の酸性条件下では、Robo2の細胞外領域のコンフォメーション変化により、NELL1が結合できるようになる。蛍光共鳴エネルギー移動(FRET)解析により、酸性条件下におけるRobo2の推定構造を取得し、NELL1-Robo2シグナルが働く分子基盤の一端を解明した。研究の進捗状況はおおむね順調であるが、現在、上記の推定構造が正しいことを証明するべく実験を進めている。
    NELL1-Robo2シグナルの役割の解明を目指して、NELL1がRobo2に結合する仕組みを明らかにする。NELL1はRobo2と酸性条件下で結合することがわかっており、それはpH変化に伴うRobo2の構造変化に起因する。今後は、FRET解析により得たRobo2細胞外領域の推定構造が正しいかどうかを他の複数の実験系を用いて解析を進める予定である。また、分担研究者である京都大学大学院農学研究科の水谷公彦先生との共同研究により、Robo2の細胞外領域の結晶構造解析を開始したが、構造解析に最適な条件を検討中であり、本年度中の解析を目指す。
    昨年、米国の研究グループにより、NELL2とRobo3の結合部位の結晶構造が報告された。Robo3はRobo2のようなヘアピン構造を取りにくいため、NELL1-Robo2の結合とは状況が異なるが、NELL1/2がRobo2/3に結合する部分のアミノ酸はかなり保存されており、NELL1がRobo2に結合する仕組みを解明するのに大変参考になる論文であった。そこで本年度は、NELL1-Robo2の結合の仕組みをアミノ酸レベルでも解析を進める。
    昨年度は、前駆骨芽細胞の酸性条件培養法の確立を試みたが、培地の作製方法の検討で終えたので、本年度は本格的に培養を開始し、酸性条件におけるNELL1-Robo2シグナルの解明に着手する。

  2. Elucidation of the molecular basis of the bone-inducing factor NELL1

    Grant number:17K01946  2017.4 - 2021.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Niimi Tomoaki

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    Authorship:Principal investigator 

    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

    The NELL1 gene was originally identified in craniosynostosis patients as being specifically upregulated within prematurely fusing sutures. Because of its potent osteoinductive activity, NELL1 protein may be useful for bone regeneration therapy. However, there is little knowledge regarding NELL1 receptors and NELL1-mediated signaling pathways. IAs a result of exploring the NELL1 receptor and elucidating the signal transduction mechanism, we identified Roundabout 2 (Robo2), which is mainly expressed in mesenchymal cells, as a novel receptor for NELL1. Furthermore, we elucidated the mode of ligand-receptor binding only under acidic conditions and suggested that it may act as a new bone formation signal.

  3. NELL1タンパク質を利用した新規骨形成因子の創成

    2014.4 - 2017.3

    科学研究費補助金  基盤研究(C)

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    Authorship:Principal investigator 

  4. 酵母で量産したヒト型ラミニンによる再生医療の新展開

    2007.3 - 2010.3

    科学研究費補助金  基盤研究(S)

    新美友章

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    Authorship:Principal investigator 

  5. 酵母で量産したヒト型ラミニンによる再生医療の新展開

    2006.4 - 2007.3

    科学研究費補助金  基盤研究(S)

    北川泰雄

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    Authorship:Coinvestigator(s) 

  6. 肺および甲状腺特異的転写因子Nkx2.1とその下流遺伝子による器官形成と機能調節

    2005.4 - 2007.3

    科学研究費補助金  若手研究(B),課題番号:17780250

    新美 友章

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    Authorship:Principal investigator 

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Teaching Experience (On-campus) 7

  1. 分子細胞生物学特論II

    2021

  2. 分子細胞生物学特論II

    2020

  3. 生物情報処理演習

    2019

  4. 分子細胞生物学特論II

    2019

  5. 基礎セミナーA

    2019

  6. 分子細胞生物学特論II

    2018

  7. 生物情報処理演習

    2018

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Academic Activities 1

  1. 日本農芸化学会中部支部庶務幹事

    Role(s):Planning, management, etc.

    2020.4 - 2022.3

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    Type:Academic society, research group, etc.