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

業績

2022

1. Yuki Miyamoto, Tomohiro Torii, Keiichi Homma, Hiroaki Oizumi, Katsuya Ohbuchi, Kazushige Mizoguchi, Shou Takashima, and Junji Yamauchi (2022) The adaptor SH2B1 and the phosphatase PTP4A1 regulate phosphorylation of cytohesin-2 in myelinating Schwann cells in mice. Sci. Signal. 15, 718
2. Sui Sawaguchi, Rimi Suzuki, Hiroaki Oizumi, Katsuya Ohbuchi, Kazushige Mizoguchi, Masahiro Yamamoto, Yuki Miyamoto, and Junji Yamauchi (2022) Hypomyelinating Leukodystrophy 8 (HLD8)-associated mutation of POLR3B leads to defective oligodendroglial morphological differentiation whose effect is reversed by ibuprofen. Neurol. Int. 14, 212-244
3. Shimizu K, Tanaka R, Iso M, Harada K, Tsuboi T, Kondo Y, Nakamura K (2022). Relationship between infantile mother preference and neural regions activated by maternal contact in C57BL/6 mice.
4. Shimizu K, Tanaka YR, Nakamura K. Difference in infantile mother preference is associated with adult anxiety/object recognition in C57BL/6 mice. Neuroscience Research. 2022. doi: 10.1016/j.neures.2022.06.004. Online ahead of print.
5. Tanaka YR, Aizawa K, Shimizu K, Akutsu H, Nakamura K. Low-density cell culture enhances hepatic function through tight junction formation in HepG2 cells. Biology of the Cell. 2022. doi: 10.1111/boc.202200002. Online ahead of print.
6. Shiori Memezawa, Takanari Sato, Arisa Ochiai, Miku Fukawa, Sui Sawaguchi, Kazunori Sango, Yuki Miyamoto, and Junji Yamauchi (2022) The antiepileptic valproic acid ameliorates Charcot-Marie-Tooth 2W (CMT2W) disease-associated HARS1 mutation-induced inhibition of neuronal cell morphological differentiation through c-Jun N-terminal kinase.Neurochem. Res. in press
7. Satoshi Nishino, Yoko Fujiki, Takanori Sato, Yukino Kato, Remina Shirai, Hiroaki Oizumi, Masahiro Yamamoto, Katsuya Ohbuchi, Yuki Miyamoto, and Junji Yamauchi (2022) Hesperetin, a citrus flavonoid, ameliorates inflammatory cytokine-mediated inhibition of oligodendroglial cell morphological differentiation.Neurol, Int. 14, 471-487 (2022)
8. Yukino Kato, Remina Shirai, Hiroaki Oizumi, Katsuya Ohbuchi, Masahiro Yamamoto, Kazushige Mizoguchi, Yuki Miyamoto, and Junji Yamauchi (2022) CRISPR/CasRx-mediated RNA knockdown reveals that ACE2 is involved in the regulation of oligodendroglial cell morphological differentiation.Noncoding RNA. 8, 42 (2022)
9. Takanori Sato, Remina Shirai, Mikinori Isogai, Katsuya Ohbuchi, Masahiro Yamamoto, Yuki Miyamoto, and Junji Yamauchi (2022) Hyaluronic acid and its receptor CD44, acting through TMEM2, inhibit morphological differentiation in oligodedroglial cells.Biochem. Biophys. Res. Commun. 624, 102-111 (2022)
10. Morita A, Shikano A, Nakamura K, Noi S, Fujiwara T. Oxytocin Reactivity during a Wilderness Program without Parents in Early Adolescents. Int J Environ Res Public Health. 2022. 19(23), 15437
11. Tanaka YR, Aizawa K, Shimizu K, Akutsu H, Nakamura K. DNMT1/PKR double knockdowned HepG2 (HepG2-DP) cells have high hepatic function and differentiation ability. Scientific Reports, 12(1). 2022. doi: 10.1038/s41598-022-25777-z.

2021

2020

1. Nawa N, Nakamura K, Fujiwara T. Oxytocin response following playful mother-child interaction in survivors of the Great East Japan Earthquake. Frontiers in Psychiatry, section Child and Adolescent Psychiatry. 2020, 3;11:477.
2. Yuki Miyamoto, Marina Tanaka, Hisanaka Ito, Hiroaki Ooizumi, Katsuya Ohbuchi, Kazushige Mizoguchi, Tomohiro Torii, and Junji Yamauchi (2020) Expression of kinase-deficient MEK2 ameliorates Pelizaeus-Merzbacher disease phenotypes in mice.　Biochem. Biophys. Res. Commun. 531, 445-451
3. Yu Takeuchi, Marina Tanaka, Nanako Okura, Yasuyuki Fukui, Ko Noguchi, Yoshihiro Hayashi, Tomohiro Torii, Hiroaki Ooizumi, Katsuya Ohbuchi, Kazushige Mizoguchi, Yuki Miyamoto, and Junji Yamauchi (2020) Rare neurologic disease-associated mutations of AIMP1 are associated with inhibitory neuronal differentiation which is reversed by ibuprofen.　Medicines 7, E25
4. Naoto Matsumoto, Yuki Miyamoto, Kohei Hattori, Akihiro Ito, Hironori Harada, Hiroaki Oizumi, Katsuya Ohbuchi, Kazushige Mizoguchi, and Junji Yamauchi (2020) PP1C and PP2A are p70S6K phosphatases whose inhibition ameliorates HLD12-associated inhibition of oligodendroglial cell morphological differentiation.　Biomedicines 8, 89
5. Umezawa A, Sato Y, Kusakawa S, Amagase R, Akutsu H, Nakamura K, Kasahara M, Matsubara Y, Igarashi T. Research and Development Strategy for Future Embryonic Stem Cell-Based Therapy in Japan. JMA J. 2020;3(4):287-294.
6. Kohei Hattori, Yu Takeuchi, Arisa Ochiai, Marina Tanaka, Sui Sawaguchi, Naoko Imaizumi, Yuki Miyamoto, and Junji Yamauchi (2020) Inhibitory effects of early infantile epileptic encephalopathy 29 (EIEE29)-associated alanyl-tRNA synthetase 1 (AARS1) mutations on neuronal differentiation.J. Clin. Mol. Med. 3, 138

2019

1. Naoto Matsumoto, Natsumi Watanabe, Noriko Iibe, Yuriko Tatsumi, Kohei Hattori, Yu Takeuchi, Hiroaki Oizumi, Katsuya Ohbuchi, Tomohiro Torii, Yuki Miyamoto, and Junji Yamauchi (2019) Hypomyelinating leukodystrophy-associated mutation of RARS leads it to the lysosome, inhibiting oligodendroglial morphological differentiation.　Biochem. Biophys. Rep. 20, 100705
2. Naoko Imaizumi, Yu Takeuchi, Haruka Hiranoa, Tomohiro Torii, Yoichi Seki, Takako Morimoto, Yuki Miyamoto, Hiroyuki Sakagami, and Junji Yamauchi (2019) Data on the effects of Charcot-Marie-Tooth disease type 2N-associated AARS missense mutation (Arg329-to-His) on the cell biological properties.　Data Brief 25, 104029
3. Yuriko Tatsumi, Naoto Matsumoto, Noriko Iibe, Natsumi Watanabe, Tomohiro Torii, Kazunori Sango, Keiichi Homma, Yuki Miyamoto, Hiroyuki Sakagami, and Junji Yamauchi (2019) CMT type 2N disease-associated AARS mutant inhibits neurite growth that can be reversed by valproic acid.　Neurosci. Res. 139, 69-78r
4. Tomohiro Torii, Yuki Miyamoto, and Junji Yamauchi: Chapter 1. Cellular Signal-Regulated Schwann Cell Myelination and Remyelination.　Basic and Clinical Advances (2019) (Springer's book) pages 3-21
5. Kohei Hattori, Arisa Ochiai, Marina Tanaka, Sui Sawaguchi, Rimi Suzuki, Natsumi Watanabe, Hiroaki Oizumi, Katsuya Ohbuchi, Yuki Miyamoto, and Junji Yamauchi (2019) Inhibitory effect of spinocerebellar ataxia type 3-associated mutant ataxin-3 on oligodendroglial cell differentiation.　J. Clin. Neurol. Neurosurg. Spine 2, 119
6. Minami Yamawaki, Masumi Akiba, Naoto Matsumoto, Natsumi Watanabe, Kohei Hattori, Yu Takeuchi, Takako Morimoto, Hiroaki Oizumi, Katsuya Ohbuchi, Yuki Miyamoto, and Junji Yamauchi (2019) Defective neuronal and oligodendroglial differentiation by FTD3- and ALS17-associated Ile29-to-Val mutation of CHMP2B.　Mol. Genet. Metab. Rep. 19, 100458

2018

1. Takizawa M, Harada K, Nakamura K, Tsuboi T.　Transient receptor potential ankyrin 1 channels are involved in spontaneous peptide hormone release from astrocytes. Biochem Biophys Res Commun. 2018 Jul 2;501(4):988-995. doi: 10.1016/j.bbrc.2018.05.097. Epub 2018 May 24.
2. Shimizu K, Nakamura K, Yokosuka M, Kondo Y.　Modulation of male mouse sociosexual and anxiety-like behaviors by vasopressin receptors.Physiol Behav. 2018 Dec 1;197:37-41. doi: 10.1016/j.physbeh.2018.09.016. Epub 2018 Oct 2
3. Miyamoto Y, Torii T, Tago K, Tanoue A, Takashima S, Yamauchi BIG1/Arfgef1 and Arf1 regulate the initiation of myelination by Schwann cells in mice. J.Sci Adv. 2018 Apr 4;4(4):eaar4471. doi: 10.1126/sciadv.aar4471. eCollection 2018 Apr.
4. Koshimizu TA, Honda K, Nagaoka-Uozumi S, Ichimura A, Kimura I, Nakaya M, Sakai N, Shibata K, Ushijima K, Fujimura A, Hirasawa A, Kurose H, Tsujimoto G, Tanoue A, Takano Y. Complex formation between the vasopressin 1b receptor, β-arrestin-2, and the μ-opioid receptor underlies morphine tolerance. Nat Neurosci. 2018 Jun;21(6):820-833. doi: 10.1038/s41593-018-0144-y. Epub 2018 Apr 30.
5. Miyamoto Y, Torii T, Tanoue A, Yamamoto M, Yamauchi The promoter region of 46-kDa CNPase is sufficient for its expression in corpus callosum. J.Mol Genet Metab Rep. 2018 Mar 13;15:78-79. doi: 10.1016/j.ymgmr.2018.03.003. eCollection 2018 Jun.

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 Brief. 11, 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 Rep. 7, 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. Role of vasopressin V1a receptor in ∆9-tetrahydrocannabinol-induced cataleptic immobilization in mice.
8. Egashira N, Koushi E, Myose T, Tanoue A, Mishima K, Tsuchihashi R, Kinjo J, Tanaka H, Morimoto S, Iwasaki K.Psychopharmacology (Berl). 2017 Dec;234(23-24):3475-3483. doi: 10.1007/s00213-017-4735-1. Epub 2017 Sep 14.PMID: 28905207 Role of vasopressin V1a receptor in ∆9-tetrahydrocannabinol-induced cataleptic immobilization in mice.
9. Torii T, Miyamoto Y, Kawahara K, Tanoue A, Seki Y, Morimoto T, Yamamoto M, Yamauchi J. Data Brief 2017 Feb 22;11:358-363. doi: 10.1016/j.dib.2017.02.042. eCollection 2017 Apr PMID:28275669 Data supporting the role of Fyn in embryonic sciatic nerve fasciculation.
10. 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. Data Brief. 2017 Feb 16;11:284-289. doi: 10.1016/j.dib.2017.02.024. eCollection 2017 Apr. PMID: 28275661 Data on the effect of hypomyelinating leukodystrophy 6 (HLD6)-associated mutations on the TUBB4A properties.
11. Nakamura K, Aizawa K, Aung KH, Yamauchi J, Tanoue A. Sci Rep. 2017 Jan 23;7:41093. doi: 10.1038/srep41093. PMID:28112215 Zebularine upregulates expression of CYP genes through inhibition of DNMT1 and PKR in HepG2 cells.

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