Masahiro Kawahara

ORCiD: 0000-0003-2301-6171
Associate professor
Departmenet of Chemistry and Biotechnology
kawahara
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Education

2002, Ph.D., The University of Tokyo
1997, B.S., The University of Tokyo

Experience

2008-2015, Lecturer, The University of Tokyo
2006-2008, JSPS Postdoctoral Fellow for Research Abroad, UMass Medical School
2002-2008, Assistant Professor, The University of Tokyo
2001-2002, JSPS Research Fellows for Young Scientists

略歴

1997年 東京大学工学部化学生命工学科卒業
2001-02年 日本学術振興会特別研究員(DC2)
2002年 東京大学大学院工学系研究科化学生命工学専攻博士課程修了
2002-07年 東京大学大学院工学系研究科化学生命工学専攻助手
2006-08年 日本学術振興会海外特別研究員(米国マサチューセッツ大学医学部病理学科)
2007-08年 東京大学大学院工学系研究科化学生命工学専攻助教 2008-15年 東京大学大学院工学系研究科化学生命工学専攻講師

Cytokines control cellular growth and differentiation through binding to their cognate receptors expressed on the cell surface. We replaced ligand-binding domain of cytokine receptors with antibody variable regions, aiming at a system to control cellular fate in response to a cognate antigen.

我々の体内では,サイトカインと呼ばれるタンパク質が細胞膜表面にある受容体と結合することで,細胞の増殖や分化をコントロールしている。当研究グループではこの受容体のサイトカイン結合部位を,抗体の抗原結合部位(抗体可変領域VH、VL)に置換したキメラ受容体を作製し,外部から加える抗原の量によって人為的に細胞の運命を制御することを目指して研究を行ってきた。

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To date, we successfully controlled growth of wide variety of cell types including hematopoietic/non-hematopoietic cells and hybridoma cells by using hen egg lysozyme or fluorescein as an antigen. We are now applying this technology to gene therapy, elucidation of intracellular signal transduction and development of antibody selection system, which could direct medical, industrial and scientific applications.

現在までに,抗原としてニワトリ卵白リゾチーム(HEL),またはフルオレセインを用いて血球細胞,ハイブリドーマ細胞,非血球細胞といった幅広い細胞の増殖制御を行うことに成功した。現在,このキメラ受容体を用いて,遺伝子治療,物質生産コスト削減,細胞内シグナル伝達の解析,動物細胞を用いた抗体取得方法の開発といった医学,工学,理学にまたがる応用を目指して研究を進めている。

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D. Kashima

Ph.D. Student
Departmenet of Chemistry and Biotechnology

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日本生物工学会 東日本支部学生奨励賞を受賞。(2017年2月25日) 第68回日本生物工学会大会においてセルプロセッシング計測評価研究部会 優秀学生発表賞(「ホモ二量体化モジュールの導入による細胞内タンパク質間相互作用検出の高感度化」)を受賞。(2016年10月)

化学工学会 第81回年会にて優秀学生賞を受賞。(2016年3月13日)

R. Zhang

Master's course Student
Departmenet of Bioengineering

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K. Umene

Master's course Student
Departmenet of Chemistry and Biotechnology

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K. Tatphon

Master's course Student
Departmenet of Chemistry and Biotechnology

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The 29th Annual and International Meeting of the Japanese Association for Animal Cell Technology (JAACT2016 Kobe)においてBest Poster Presentation Awardを受賞。(2016年11月12日)

A. Eguchi

Master's course Student
Departmenet of Chemistry and Biotechnology

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The 29th Annual and International Meeting of the Japanese Association for Animal Cell Technology (JAACT2016 Kobe)においてBest Oral Presentation Awardを受賞。(2016年11月12日)

第68回日本生物工学会大会においてセルプロセッシング計測評価研究部会 優秀学生発表賞(「細胞死シグナルを利用したタンパク質間相互作用阻害分子選択法の開発」)を受賞。(2016年10月)

Y. Kakiuchi

Master's course Student
Departmenet of Bioengineering

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R. Kashimoto

Undergraduate Student
Departmenet of Chemistry and Biotechnology

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M. Kawakami

Undergraduate Student
Departmenet of Chemistry and Biotechnology

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OB/OG

T. D. Nguyen (BS, 2011.4~2012.3; MS, 2012.4~2014.3; PhD, 2014.4~2017.3)
H. NaKaBayashi (BS, 2010.4~2011.3; MS, 2011.4~2013.3; PhD, 2013.4~2016.3; Post-doc, 2016.4~2017.3)
S. Araki (BS, 2016.4~2017.3)
M. Kageoka (BS, 2013.4~2014.3; MS, 2014.4~2016.3)
S. Shin (BS, 2013.4~2014.3; MS, 2014.4~2016.3)
Y. Sumigama (BS, 2013.4~2014.3; MS, 2014.4~2016.3)
T. Wong (MS, 2013.10~2015.9)
T. Miura (BS, 2012.4~2013.3; MS, 2013.4~2015.3)
S. Ishizuka (BS, 2012.4~2013.3; MS, 2013.4~2015.3)
R. Kawade (BS, 2014.4~2015.3)
N. Hattori (BS, 2014.4~2015.3)
B. Sun (PhD, 2011.10~2014.9)
S. Mabe (BS, 2011.4~2012.3; MS, 2012.4~2014.3)
K. Saka (BS, 2011.4~2012.3; MS, 2012.4~2014.3)
S. Honda (BS, 2011.4~2012.3; MS, 2012.4~2014.3)
S. H. Lee (MS, 2011.4~2013.3)
Y. Ma (MS, 2011.4~2013.3)
R. Yoshida (MS, 2011.4~2013.3)
S. Aoyama (BS, 2011.4~2012.3)
Y. Teranishi (BS, 2009.4~2010.3; MS, 2010.4~2012.3)
Y. Tone (BS, 2009.4~2010.3; MS, 2010.4~2012.3)
K. Ogawa (BS, 2008.4~2009.3; MS, 2009.4~2011.3)
A. Touno (MS, 2009.4~2011.3)
H. Takasuka (MS, 2009.4~2011.3)
J. Teng (MS, 2008.4~2010.3)
T. Sogo (BS, 2002.4~2003.3; MS, 2003.4~2005.3; PhD, 2005.4~2009.4)
W. Liu (MS, 2004.4~2006.3; PhD, 2006.4~2009.3)
J. Hayashi (BS, 2006.4~2007.3; MS, 2007.4~2009.3)
Y. Mochida (BS, 2008.4~2009.3)
A. Hitomi (BS, 2007.4~2008.3)
J. Chen (MS, 2006.4~2008.3)
N. Suzuki (BS, 2006.4~2007.3)
K. Tanaka (MS, 2004.4~2007.3)
Y. Simo (BS, 2005.4~2006.3)
D. Kawaguchi (BS, 2003.4~2004.3)
H. Kimura (BS, 2001.4~2002.3; MS, 2002.4~2004.3)
E. Kaneko (BS, 2001.4~2002.3; MS, 2002.4~2004.3)

Y. Ogo (BS, 2002.4~2003.3)
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S. Ishii (MS, 2000.4~2002.3)
A. Natume (BS, 1999.4~2000.3; MS, 2000.4~2002.3)

Publications in 2016

  • H. Nakabayashi, S. Aoyama, M. Kawahara*, T. Nagamune, "Differentiation signalobody: Demonstration of antigen-dependent osteoclast differentiation from a progenitor cell line", J. Biosci. Biotechnol., 122, 357–363 (2016).
    PMID: 26979343
  • S. Lee, Y. Kaku, S. Inoue, T. Nagamune, M. Kawahara*, "Growth signalobody selects functional intrabodies in the mammalian cytoplasm", Biotechnol. J., 11, 565–573 (2016).
    26647155
  • T. Miura, T. Nagamune and M. Kawahara*, "SLigand-inducible dimeric antibody for selecting antibodies against a membrane protein based on mammalian cell proliferation", Biotechnol. Bioeng., 113, 1113–1123 (2016).
    26479395

Publications in 2015

  • R. Yoshida, T. Nagamune and M. Kawahara*, "Domain structure of growth signalobodies critically affects the outcome of antibody library selection", J. Biochem., 157, 497-506 (2015).
    PMID: 25616678
  • S. Honda, T. Nagamune and M. Kawahara*, "Selection of cDNA candidates that induce oligomerization of NLRP3 using a chimeric receptor approach", J. Biosci. Bioeng., 120, 223-230 (2015).
    PMID: 25641579

Publications in 2014

  • S. Yamahira, S. Yamaguchi,*, M. Kawahara and T. Nagamune*, "Collagen Surfaces Modified with Photo-Cleavable Polyethylene Glycol-Lipid Support Versatile Single-Cell Arrays of Both Non-adherent and Adherent Cells", Macromol. Biosci., 14, 1670-1676 (2014).
    PMID: 25195937
  • S. Mabe, T. Nagamune and M. Kawahara*, "Detecting protein-protein interactions based on kinase-mediated growth induction of mammalian cells", Sci. Rep., 4, 6127 (2014).
    PMID: 25135216
  • Y. Ma, T. Nagamune and M. Kawahara*, "Split focal adhesion kinase for probing protein–protein interactions", Biochem. Eng. J., 90, 272-278 (2014).
  • B. Sun, M. Kawahara and T. Nagamune*, "Modeling tandem AAG8-MEK inhibition in melanoma cells", Cancer Med., 3, 710-718 (2014).
    PMID: 24634165
  • B. Sun, M. Kawahara, S. Ehata and T. Nagamune*, "AAG8 promotes carcinogenesis by activating STAT3", Cell Signal., 26, 1863-1869 (2014).
    PMID: 24726897
  • M. Kawahara*, A. Hitomi and T. Nagamune "S-Fms signalobody enhances myeloid cell growth and migration", Biotechnol. J., 9, 954-961 (2014).
    PMID: 24376185
  • M. Kawahara*, A. Hitomi and T. Nagamune, "Antigen-responsive regulation of cell motility and migration via the signalobodies based on c-Fms and c-Mpl", Biotechnol. Prog., 30, 411-417 (2014).
    PMID: 24375974
  • R. Yoshida, M. Kawahara*, and T. Nagamune, "A novel platform for antibody library selection in mammalian cells based on a growth signalobody", Biotechnol. Bioeng., 111, 1170-1179 (2014).
    PMID: 24338724
  • K. Saka, M. Kawahara*, and T. Nagamune, "Quantitative control of intracellular signaling activity through chimeric receptors incorporating multiple identical tyrosine motifs", Biotechnol. Bioeng., 111, 948-955 (2014).
    PMID: 24222636

Publications in 2013

  • K. Saka, M. Kawahara*, J. Teng, M. Otsu, H. Nakauchi and T. Nagamune, "Top-down motif engineering of a cytokine receptor for directing ex vivo expansion of hematopoietic stem cells", J. Biotechnol., 168, 659-665(2013).
    PMID: 24070902
  • K. Ogawa, M. Kawahara*, and T. Nagamune, "Construction of unnatural heterodimeric receptors based on IL-2 and IL-6 receptor subunits", Biotechnol. Prog., 29, 1512-1518 (2013).
    PMID: 23926072
  • K. Saka, M. Kawahara* and T.Nagamune, "Reconstitution of a cytokine receptor scaffold utilizing multiple different tyrosine motifs", Biotechnol. Bioeng., 110, 3197-3204 (2013).
    PMID: 23775041
  • Y. Tone, M. Kawahara*, J. Hayashi and T. Nagamune, "Cell fate conversion by conditionally switching the signal-transducing domain of signalobodies", Biotechnol. Bioeng., 110, 3219-3226 (2013).
    PMID: 23794462
  • Y. Tone, M. Kawahara*, D. Kawaguchi, H. Ueda and T. Nagamune, "Death signalobody: Inducing conditional cell death in response to a specific antigen", Hum. Gene Ther. Methods., 24, 141-150 (2013).
    PMID: 23470213
  • H. Nakabayashi, M. Kawahara*, K. Tanaka and T. Nagamune, "Construction of antibody/insulin receptor chimera for growth induction of mammalian cells", Cytotechnology, 65, 945-953 (2013).
    PMID: 23615961
  • T. Inagaki, T. Yoshimi, S. Kobayashi, M. Kawahara and T. Nagamune*, " Analysis of cellular phenotype during in vitro immunization of murine splenocytes for generating antigen-specific immunoglobulin ", J. Biosci. Bioeng., 115, 339-345 (2013).
    PMID: 23177212

Publications in 2012

  • M. Kawahara and T. Nagamune*, " Engineering of mammalian cell membrane proteins ", Current Opin. Chem. Eng., 1, 411-417 (2012).
  • K. Saka, M. Kawahara*, H. Ueda and T. Nagamune, " Activation of target signal transducers utilizing chimeric receptors with signaling-molecule binding motifs ", Biotechnol. Bioeng., 109, 1528-1537 (2012).
    PMID: 22228507
  • E. Kaneko, M. Kawahara*, H. Ueda and T. Nagamune, " Growth control of genetically modified cells using an antibody/c-Kit chimera ", J. Biosci. Bioeng., 113, 641-646 (2012).
    PMID: 22227120

Publications in 2011

  • M. Kawahara*, J. Chen, T. Sogo, J. Teng, M. Otsu, M. Onodera, H. Nakauchi, H. Ueda and T. Nagamune, " Growth promotion of genetically modified hematopoietic progenitors using an antibody/c-Mpl chimera ", Cytokine, 55, 402-408 (2011).
    PMID: 21700475
  • M. Kawahara, H. Ueda, and T.Nagamune, "Engineering cytokine receptors to control cellular functions", Biochem. Eng. J., 48, 283-294 (2010).

Publications in 2009

  • M. Kawahara, I.A. York, A. Hearn, D. Farfan and K.L. Rock* "Analysis of the role of tripeptidyl peptidase II in MHC class I antigen presentation in vivo", J. Immunol., 183, 6069-6077 (2009).
    PMID: 19841172
  • "Tanaka, K., Kawahara, M., Ueda, H. and Nagamune, T., "Selection and growth regulation of genetically modified cells with hapten-specific antibody/receptor tyrosine kinase chimera", Biotechnol. Prog., 25, 1138-1145 (2009).
    PMID: 19569211
  • Liu, W., Kawahara, M., Ueda, H. and Nagamune, T., "The influence of domain structures on the signal transduction of chimeric receptors derived from the erythropoietin receptor", J. Biochem., 145, 575-584 (2009).
    PMID: 19155265
  • Sogo, T., Kawahara, M., Ueda, H., Otsu, M., Onodera, M., Nakauchi, H. and Nagamune, T., "T cell growth control using hapten-specific antibody/interleukin-2 receptor chimera", Cytokine, 46, 127-136 (2009).
    PMID: 19223197

Publications in 2008

  • Liu, W., Kawahara, M., Ueda, H. and Nagamune, T.,"Construction of a fluorescein-responsive chimeric receptor with strict ligand dependency", Biotechnol. Bioeng., 101, 975-984 (2008).
    PMID: 18500765
  • Kawahara, M., Shimo, Y., Sogo, T., Hitomi, A., Ueda, H. and Nagamune, T.,“Antigen-mediated migration of murine pro-B Ba/F3 cells via an antibody/receptor chimera", J. Biotechnol., 133, 154-161(2008).
    MID: 17961783
  • Sogo, T., Kawahara, M., Tsumoto, K., Kumagai, I., Ueda, H. and Nagamune, T., "Selective expansion of genetically modified T cells using an antibody/interleukin-2 receptor chimera", J. Immunol. Methods, 337, 16-23 (2008).
    PMID: 18589435

Publications in 2007

  • Kawahara, M., Inoue,T., Ren, X., Sogo, T., Yamada, H., Katoh, M., Ueda, H., Oshimura, M. and Nagamune, T., "Antigen-mediated growth control of hybridoma cells via a human artificial chromosome", Biochemica et Biophysica Acta - GENERAL SUBJECTS-, 1770, 206-212 (2007).
    PMID: 17184921
  • Kawahara, M., Ueda, H., Tsumoto, K., Kumagai, I. and Nagamune, T., "Mimicry of erythropoietin and interleukin-6 signaling by an antibody/cytokine receptor chimera in murine myeloid 32D cells", J. Biochem., 141, 563-571 (2007).
    PMID: 17442704

Publications in 2006

  • Kawahara, M., Ogo, Y., Tsumoto, K., Kumagai, I., Ueda , H. and Nagamune, T., "Growth control of hybridoma cells with an artificially induced EpoR-gp130 heterodimer", Cytotechnology, 52, 171-179(2006).
    PMID: 19002875
  • Yamada, H., Kunisato, A., Kawahara, M., Tahimic, C. G. T., Ren, X., Ueda, H., Nagamune, T., Katoh, M., Inoue, T., Nishikawa, M. and Oshimura, M. (2006), "Exogenous Gene Expression and Growth Regulation of Hematopoietic Cells via a Novel Human Artificial Chromosome", J. Hum. Genet. 51, 147-150.
    PMID: 16333524

Publications in 2004

  • Pihkala, P., Kawahara, M., Ueda, H., and Nagamune, T. (2004) "An antigen-mediated selection system for mammalian cells that produce glycosylated single-chain Fv." Biochem. Biophys. Res. Commun. 324, 1165-1172.
    PMID: 15504336
  • Kaneko, E., Kawahara, M., Tsumoto, K., Kumagai, I., Ueda, H., and Nagamune, T. (2004) "Antigen-mediated genetically modified cell amplification (AMEGA) with single vector transduction." J. Chem. Eng. Jpn. 37, 1259-1264.
  • Kimura, H., Kawahara, M., Tomlinson, I.M., Ueda, H., and Nagamune, T. (2004) "Cell proliferation switch responsive to fluorescein dimer." Animal Cell Technology: Basic & Applied Aspects (Yagasaki, K., Ed.), 13., Kluwer Academic Publishers, Dordrecht, 335-339.
  • Kawahara, M., Ogo, Y., Ueda, H., and Nagamune, T. (2004) "Improved growth response of antibody/receptor chimera attained by the engineering of transmembrane domain." Protein Eng. Des. Sel. 17, 715-719.
    PMID: 15548567
  • Kawahara, M., Ishii, S., Tsumoto, K., Kumagai, I., Ueda, H. & Nagamune, T.(2004) "Reversal of antigen-dependent signaling by two mutation in antibody/receptor chimera: implication of inverse agonism in cytokine receptor superfamily" Biochem. Pharmacol. 68(3), 539-548.
    PMID: 15242820
  • Kawahara, M., Ueda, H., Tsumoto, K., Kumagai, I. & Nagamune, T.(2004)"AMEGA: antigen-mediated genetically modified cell amplification." J. Immunol. Methods. 284 (1-2) 187-194.
    PMID: 14736429
  • Kawahara, M., Kimura, H., Ueda, H. & Nagamune, T.(2004)"Selection of genetically modified cell population using hapten-specific antibody/receptor chimera." Biochem. Biophys. Res. Commun. 315, 132-138.
    PMID: 15013436

Publications in 2003

  • Kawahara, M.,Ueda, H.,Morita, S.,Tsumoto, K.,Kumagai, I. & Nagamune, T.(2003)"Bypassing antibiotic selection positivescreening of genetically modified cells with an antigen-dependent proliferation switch" Nucleic Acids Res. 31 (7) e32.
    PMID: 12655020

Publications in 2002

  • Kawahara, M., Ueda, H., Tsumoto, K., Kumagai, I., Mahoney, W. & Nagamune, T.(2002) "Selection of highly productive mammalian cells based on an inducible growth advantage using an antibody/receptor chimera." J. Biosci. Bioeng. 93 (4), 399-404.
    PMID: 16233221
  • Kawahara, M.,Ueda, H.,Tsumoto, K.,Kumagai, I.,Mahoney, W., and Nagamune, T.(2002) ACS SYMPOSIUM SERIES 830,140-151,Biological System Engineering chapter11 "Antigen-mediated genetically modified cell amplification."

Publications in 2001

  • Kawahara, M., Natsume, A., Terada, S., Kato, K., Tsumoto, K., Kumagai, I., Miki, M., Mahoney, W., Ueda, H. & Nagamune, T. (2001). "Replacing factor dependency with that for lysozyme: Affordable culture of IL-6 dependent hybridoma by transfecting artificial cell surface receptor." Biotechnol. Bioeng. 74(5), 416-423.
    PMID: 11427943
  • Kawahara, M., Ueda, H., Tsumoto, K., Kumagai, I., Mahoney, W. & Nagamune, T. (2001). "A growth signal with an artificially induced erythropoietin receptor-gp130 cytoplasmic domain heterodimer." J. Biochem. 130(2), 305-312.
    PMID: 11481050

Publications in 2000

  • H. Ueda*, M. Kawahara, T. Aburatani, K. Tsumoto, K. Todokoro, E. Suzuki, H. Nishimura, P.A. Schueler, G. Winter, W. C. Mahoney, I. Kumagai and T.Nagamune, " Cell-growth control by monomeric antigen; the cell surface expression of lysozyme-specific Ig V-domains fused to truncated Epo receptor ", J. Immunol. Methods, 241 (1-2), 159-170 (2000).
    PMID: 10915858

Books and Proceedings

  • Kawahara, M., Inoue, T., Ren, X., Sogo, T., Yamada, H., Katoh, M., Ueda, H., Oshimura, M. and Nagamune, T. "Growth control of mammalian cells via a human artificial chromosome harboring a chimeric receptor.", Proceedings of the 21st Annual and International Meeting of the Japanese Association for Animal Cell Technology (JAACT), November 24-27, 2008, Fukuoka, Japan, Animal Cell Technology: Basic & Applied Aspects, vol.16, pp 253-258 (2010).
  • Liu, W., Kawahara, M., Ueda, H., and Nagamune, T. "The characteristic of chimeric receptors based on erythropoietin receptor.", Proceedings of the 21st Annual and International Meeting of the Japanese Association for Animal Cell Technology (JAACT), November 24-27, 2008, Fukuoka, Japan, Animal Cell Technology: Basic & Applied Aspects, vol.16, pp. 265-270 (2010).
  • Kawahara, M., Ueda, H., Tsumoto, K., Todokoro, K., Mahoney, W., Kumagai, I., and Nagamune, T.,"Monovalent antigen activates antibody/cytokine receptor chimera and controls hematopoietic cell growth", Animal Cell Technology: Challenges for the 21st Century(JAACT/ESACT), R.Sasaki et al.(Eds), Kluwer Academic Publishers, 255-259(1999).