国立研究開発法人 国立成育医療研究センター National Center for Child Health and Development

代表: 03-3416-0181 / 予約センター(病院): 03-5494-7300
〈月~金曜日(祝祭日を除く)9時〜17時〉

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研究者・企業の方へ Scholar & Enterprise

研究者・企業の方へ Scholar & Enterprise

薬剤治療研究部

研究部紹介

小児難治性疾患における新たな薬物標的分子の探索や機能解析による創薬研究を行い、小児・妊婦(胎児)における薬物療法の確立を行っています。また、薬物の発生発達毒性の評価とその発現機序の検討を行い、小児・妊婦における安心・安全な薬物療法を科学的に検討しています。
いずれも、分子生物学的、分子細胞生物学的、生物化学的、組織学的、分子生理学的手法等を用い、多角的な観点から小児難治性疾患に対する基礎医学研究を行っています。


研究内容

1. 神経内分泌系による神経発達制御と神経発達障害に関する研究

    神経内分泌系、特に下垂体後葉ホルモンによる神経発達制御機構を明らかにし、下垂体ホルモン系の破綻による神経発達障害の発症機序について検討を行っています。

2. 下垂体における細胞分化機構、ホルモン産生機構に関する研究

    下垂体前葉のホルモン産生細胞の分化やホルモン産生・分泌に関して、特にmicroRNAによる遺伝子発現制御機構を中心に検討を行っています。   

3. 細胞を用いたin vitro薬物毒性試験法の開発および安全性評価

     肝細胞培養株の高機能化をめざし、in vitroでの肝毒性試験への応用を検討しています。また、ES/iPS細胞を用いた発生毒性試験法や肝細胞、神経細胞等を用いた組織特異的薬物毒性試験法の開発および薬物の安全性評価と薬物毒性発現機序の検討を行っています。

4. 新規病態モデル動物の開発

    モデル動物が現存しない疾患に関して、遺伝子改変技術等を応用し、疾患のモデル動物の開発を行い、創薬標的分子の探索や治療への橋渡し研究を行っています。


スタッフ

薬剤治療研究部

  • 田上 昭人(部長)

分子薬理研究室

実験薬理研究室

業績

2017

  1. Nakamura K, Velho G, Bouby N. Vasopressin and metabolic disorders: translation from experimental models to clinical use. J Intern Med. 2017
  2. Harada K, Kitaguchi T, Kamiya T, Kyaw Htet Aung, Nakamura K, Ohta K, Tsuboi T. (2017)Lysophosphatidylinositol-induced activation of the cation channel TRPV2 triggers glucagon-like peptide-1 secretion in enteroendocrine L cells. Journal of Biological Chemistry. 292, 10855-10864.
  3. Maekawa F, Nakamura K, Nakayama SF. Editorial: Chemicals in the Environment and Brain Development: Importance of Neuroendocrinological Approaches. Front Neurosci. (2017) Mar 21;11:133.
  4. Miyamoto Y, Torii T, Kawahara K, Hasegawa N, Tanoue A, Seki Y, Morimoto T, Funakoshi-Tago M, Tamura H, Homma K, Yamamoto M, Yamauchi J. (2017) Data on the effect of hypomyelinating leukodystrophy 6 (HLD6)-associated mutations on the TUBB4A properties. Data Brief. 11, 284-289.
  5. Torii T, Miyamoto Y, Kawahara K, Tanoue A, Seki Y, Morimoto T, Yamamoto M, Yamauchi J. (2017) Data supporting the role of Fyn in embryonic sciatic nerve fasciculation. Data Brief11, 358-363.

  6. Nakamura K, Aizawa K, Aung KH, Yamauchi J, Tanoue A(2017) Zebularine upregulates expression of CYP genes through inhibition of DNMT1 and PKR in HepG2 cells. Sci Rep7, 41093.

  7. Miyamoto Y, Torii T, Tanoue A, Kawahara K, Arai M, Tsumura H, Ogata T, Nagao M, Terada N, Yamamoto M, Takashima S, Yamauchi J(2017) Neuregulin-1 type III knockout mice exhibit delayed migration of Schwann cell precursors. Biochem Biophys Res Commun. S0006-291X(17)30540-5. 

2016

  1. Tomohiro Torii, and Junji Yamauchi (2016) Gas6-Tyro3 signaling is required for Schwann cell myelination and possible remyelination. Neural Regen. Res. 11, 215-216.

  2. Aung KH, Kyi-Tha-Thu C, Sano K, Nakamura K, Tanoue A, Nohara K, Kakeyama M, Tohyama C, Tsukahara S, Maekawa F. Prenatal exposure to arsenic impairs behavioral flexibility and cortical structure in mice. Front. Neurosci., 2016. doi: 10.3389/fnins.2016.00137.

  3. Naoko Niimi, Masami Tsukamoto, Shizuka Takaku, Junji Yamauchi, Emiko Kawakami, Hiroko Yanagisawa, Kazuhiko Watabe, Kazunori Utsunomiy, and Kazunori Sango (2016) Involvement of oxidative stress and impaired lysosomal degradation in amiodarone-induced schwannopathy. Eur. J. Neurosci. in press

  4. Magdalena Sobczak, Vira Chumak, Pawel Pomorski, Emilia Wojtera, Lukasz Majewski, Jolanta Nowak, Junji Yamauchi, and Maria Jolanta Redowicz (2016) Interaction of myosin VI and its binding partner DOCK7 plays an important role in NGF-stimulated protrusion formation in PC12 cells. Biochim. Biophys. Acta (BBA) Mol. Cell Res. 1863 1589-1560

  5. Yuki Miyamoto, Tomohiro Torii, Kazuko Kawahara, Akito Tanoue, and Junji Yamauchi* (2016) Dock8 interacts with Nck1 in mediating Schwann cell precursor migration. Biochem. Biophys. Rep. 6, 113-123

  6. Yuki Miyamoto, Moe Tamano, Tomohiro Torii, Kazuko Kawahara, Kazuaki Nakamura, Akito Tanoue, Shuji Takada, and Junji Yamauchi* (2016) Data supporting the role of Fyn in initiating myelination in the peripheral nervous system. Data Brief 7:1098-105

  7. Yuki Miyamoto, Megumi Funakoshi-Tago, Nanami Hasegawa, Takahiro Eguchi, Akito Tanoue, Hiroomi Tamura, and Junji Yamauchi* (2016) Data supporting mitochondrial morphological changes by spastic paraplegia (SPG) 13-associated HSPD1 mutants. Data Brief 6, 482-488

  8. Kohji Nishimura, Erika Matsunami, Shohei Yoshida, Shuhei Kohata, Junji Yamauchi, Mitsuo Jisaka, Tsutomu Nagaya, Kazushige Yokota, and Tsuyoshi Nakagawa (2016) The tyrosine-sorting motif of the Arabidopsis vacuolar sorting receptor VSR4, which is involved in the interaction between VSR4 and AP1M2, 1-adaptin type 2, of clathrin adaptor complex 1 subunits, participates in the post-Golgi sorting of VSR4.
    Biosci. Biotech. Biochem. 80, 694-705

2015

  1. Tomohiro Torii, and Junji Yamauchi (2015) A new signalsome containing cytohesin-2 and CCDC120 controls neurite outgrowth. Med. Res. Arch. 2, 19:.

  2. Aung KH, Tsukahara S, Maekawa F, Nohara K, Nakamura K, Tanoue A. Role of Environmental Chemical Insult in Neuronal Cell Death and Cytoskeleton Damage. Biol Pharm Bull. 2015;38(8):1109-12.

  3. Kohji Nishimura, Syouta Ishikawa, Erika Matsunami, Junji Yamauchi, Keiichi Homma, Christine Faulker, Karl Oparka, Mitsuo Jisaka, Tsutomu Nagaya, Kazushige Yokota, and Tsuyoshi Nakagawa (2015) New Gateway compatible vectors for a high-throughput protein-protein interaction analysis by a bimolecular fluorescence complementation (BiFC) assay and their application to an Arabidopsis clathrin structure analysis. Biosci. Biotech. Biochem. 79, 1995-2006

  4. Tomohiro Torii, Yuki Miyamoto, Masahiro Yamamoto, Katsuya Ohbuchi, Hideki Tsumura, Kazuko Kawahara, Akito Tanoue, Hiroyuki Sakagami, and Junji Yamauchi (2015) Data supporting Arf6 regulation of Schwann cell differentiation and myelination. Data Brief 5, 388-395

  5. Yuki Miyamoto, Tomohiro Torii, Shuji Takada, Nobuhiko Ohno, Yurika Saitoh, Kazuaki Nakamura, Akihito Ito, Toru Ogata, Nobuo Terada, Akito Tanoue, and Junji Yamauchi (2015) Involvement of the Tyro3 receptor and its intracellular partner Fyn signaling in Schwann cell myelination. Mol. Biol. Cell 26, 3489-3503

  6. Tomohiro Torii, Yuki Miyamoto, Masahiro Yamamoto, Katsuya Ohbuchi, Hideki Tsumura, Kazuko Kawahara, Akito Tanoue, Hiroyuki Sakagami, and Junji Yamauchi* (2015) Arf6 mediates Schwann cell differentiation and myelination. Biochem. Biophys. Res. Commun. 465, 450-457

  7. Yu Tezuka, Natsumi Herai, Yui Inomata, Keisuke Kagami, Junji Yamauchi, Hideo Nishigori, and Atsushi Sanbe (2015) Upregulation of inorganic pyrophosphatase 1 as a JNK phosphatase in hypothyroid embryonic chick cerebellum. Life Sci. 128, 94–100

  8. Miyamoto Y, Eguchi T, Kawahara K, Hasegawa N, Nakamura K, Funakoshi-Tago M, Tanoue A, Tamura H, Yamauchi J. Hypomyelinating leukodystrophy-associated missense mutation in HSPD1 blunts mitochondrial dynamics. Biochemical and Biophysical Research Communications, 2015, 462, 275-81.

  9. Nakamura K, Nakabayashi K, Kyaw Htet Aung, Aizawa K, Hori N, Yamauchi J, Hata K, Tanoue A. DNA methyltransferase inhibitor zebularine induces human cholangiocarcinoma cell death through alteration of DNA methylation status. PLoS ONE 2015, 10(3): e0120545. doi:10.1371/journal.pone.0120545. 

  10. Torii T, Ohno N, Miyamoto Y, Kawahara K, Saitoh Y, Nakamura K, Takashima S, Sakagami H, Tanoue A, Yamauchi J. Arf6 guanine-nucleotide exchange factor cytohesin-2 regulates myelination in nerves. Biochemical and Biophysical Research Communications, 2015, 460, 819-25.

2014

  1. Tomohiro Torii, Yuki Miyamoto, Junji Yamauchi, and Akito Tanoue (2014) Pelizaeus-Merzbacher disease: cellular pathogenesis and pharmacologic therapies. Pediatr. Int. 56, 659-666

  2. Torii T, Miyamoto Y, Tago K, Sango K, Nakamura K, Sanbe A, Tanoue A, Yamauchi J. Arf6 guanine-nucleotide exchange factor cytohesin-2 binds to CCDC120 and is transported along neurites to mediate neurite growth. J Biol Chem. 2014, 289, 33887-903.
  3. Torii T, Miyamoto Y, Takada S, Tsumura H, Arai M, Nakamura K, Ohbuchi K, Yamamoto M, Tanoue A, Yamauchi J. In vivo knockdown of ErbB3 in mice inhibits Schwann cell precursor migration. Biochem Biophys Res Commun. 2014, 452, 782-8.
  4. Suemizu H, Nakamura K, Kawai K, Higuchi Y, Kasahara M, Fujimoto J, Tanoue A, Nakamura M. Hepatocytes buried in the cirrhotic livers of biliary atresia patients proliferate and function in the liver of uPA-NOG mice. Liver Transplantation. 2014, 20, 1127-37.
  5. Miyamoto Y, Torii T, Eguchi T, Nakamura K, Tanoue A, Yamauchi J. Hypomyelinating leukodystrophy-associated missense mutant of FAM126A/hyccin/DRCTNNB1A aggregates in the endoplasmic reticulum. JOURNAL OF CLINICAL NEUROSCIENCE. 2014 21, 1033-9.
  6. Akama T, Luo Y, Sellitti DF, Kawashima A, Tanigawa K, Yoshihara A, Ishido Y, Nakamura K, Tanoue A, Suzuki K: Thyroglobulin increases thyroid cell proliferation via the suppression of specific microRNAs. Molecular Endocrinology. 2014 Jan; 30:me20131266.
  7. Miyamoto Y, Yamamori N, Torii T, Tanoue A, Yamauchi J. Rab35, acting through ACAP2 switching off Arf6, negatively regulates oligodendrocyte differentiation and myelination. Moecular Biology of the Cell. 2014 May; 25(9): 1532-1542 論文掲載号の表紙に採用された。
  8. Enosawa S, Horikawa R, Yamamoto A, Sakamoto S, Shigeta T, Nosaka S, Fujimoto J, Nakazawa A, Tanoue A, Nakamura K, Umezawa A, Matsubara Y, Matsui A, Kasahara M:Hepatocyte transplantation using the living donor reduced-graft in a baby with ornithine transcarbamylase deficiency: A novel source for hepatocytes. Liver Transplantation. 2014; 20:391-393.
  9. Suemizu H, Nakamura K, Kawai K, Higuchi Y, Kasahara M, Fujimoto J, Tanoue A, Nakamura M. Hepatocytes buried in the cirrhotic livers of patients with biliary atresia proliferate and function in the livers of urokinase-type plasminogen activator-NOG mice. Liver Transplantation. 2014; 20: 1127-1137.
  10. Miyamoto Y, Torii T, Eguchi T, Nakamura K, Tanoue A, Yamauchi J. Hypomyelinating leukodystrophy-associated missense mutant of FAM126A/hyccin/DRCTNNB1A aggregates in the endoplasmic reticulum. Journal of Clinical Neuroscience. 2014 Jun;21(6):1033-1039 
  11. Torii T, Miyamoto Y, Takada S, Tsumura H, Arai M, Nakamura K, Ohbuchi K, Yamamoto M, Tanoue A, Yamauchi J:In vivo knockdown of ErbB3 in mice inhibits Schwann cell precursor migration. Biochemical and Biophysical Research Communications. 2014;452:782-788.
  12. Degang Y, Nakamura K, Akama T, Ishido Y, Luo Y, Ishii N, Suzuki K. Leprosy as a model of immunity. Future Microbiology 2014, 9(1):43-54.
  13. Torii T, Miyamoto Y, Tago K, Sango K, Nakamura K, Sanbe A, Tanoue A, Yamauchi J:Arf6 Guanine Nucleotide Exchange Factor Cytohesin-2 Binds to CCDC120 and Is Transported Along Neurites to Mediate Neurite Growth. The Journal of Biological Chemistry 2014; 289(49): 33887-33890

2013

  1. Yasuoka Y, Kobayashi M, Sato Y, Zhou M, Abe H, Okamoto H, Nonoguchi H, Tanoue A, Kawahara K: The intercalated cells of the mouse kidney OMCDis are the target of the vasopressin V1a receptor axis for urinary acidification. Clinical and Experimental nephrology. 2013; 17: 783-792.
  2. Tezuka Y, Okada M, Tada Y, Yamauchi J, Nishigori H, Sanbe A:Regulation of neurite growth by inorganic pyrophosphatase 1 via JNK dephosphorylation. PLoS One, 2013 Apr 23; 8:e616492. 
  3. Terada N, Saitoh Y, Ohno N, Komada M, Yamauchi J, Ohno S: Involvement of Src in the membrane skeletal complex, MPP6-4.1G, in Schmidt-Lanterman incisures of mouse myelinated nerve fibers in PNS.   Histochemistry and Cell Biology 2013 Aug;140(2):213-22
  4. Miyamoto Y, Torii T, Nakamura K, Takashima S, Sanbe A, Tanoue A, Yamauchi J: Signaling through Arf6 guanine-nucleotide exchange factor cytohesin-1 regulates migration in Schwann cells. Cellular Signaling  2013; 25: 1379-1387.
  5. Torii T, Miyamoto Y, Onami N, Tsumura H, Nemoto N, Kawahara K, Kato M, Kotera J, Nakamura K, Tanoue A, Yamauchi J: In vivo expression of the Arf6 guanine-nucleotide exchange factor cytohesin-1 in mice exhibits enhanced myelin thickness in nerves. Journal of Molecular Neuroscience. 2013; 51, 522-531
  6. Nakamura K, Aizawa K, Yamauchi J, Tanoue A: Hyperforin inhibits cell growth and differentiation in mouse embryonic stem cells. Cell Proliferation. 2013 46, 529-537. 
  7. Sanbe A, Marunouchi T, Abe A, Tezuka Y, Okada M, Aoki S, Tsumura H, Yamauchi J, Tanonaka K, Nishigori H, Tanoue A:Phenotype of cardiomyopathy in cardiac-specific heat shock protein B8 K141N transgenic mouse The Journal of Biological Chemistry. 2013;288:8910-8921
  8. Nakamura K, Tanoue A.  Etiology of biliary atresia as a developmental anomaly: Recent advances. Journal of Hepato-Biliary-Pancreatic Sciences. 2013, 20(5):459-464.
  9. Miyamoto Y, Torii T, Yamamori N, Ogata T, Tanoue A, Yamauchi j:Akt and PP2A reciprocally regulate the guanine nucleotide exchange factor Dock6 to control axon growth of sensory neurons. Science Signaling. (サイエンス姉妹誌) 2013;6, ra15: 論文掲載号の表紙に採用された。また、朝日新聞に報道された。