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

周産期病態研究部

研究部紹介

胎児と胎児付属物(胎盤)の発生・分化異常や、それに伴う周産期(妊娠後期から新生児早期まで)の病気の解明を目指しています。分子生物学的手法に加え、ゲノム・エピゲノムの観点から病態を理解し、ポストゲノムシークエンス時代の、新たな周産期医療に資する研究成果を目標としています。
周産期ゲノミクス研究室、胎児発育研究室、母性管理研究室の三研究室が中心となって、生殖細胞の形成から出生に至るまで、広く母体と胎児(新生児)と胎盤に関する研究を行っています。


研究内容

周産期の異常は、母子双方に対して緊急かつ集学的な医療介入が必要になります。しかし、周産期に起こる疾患の詳細なメカニズムは未解明な点が多く、早期の診断や根治的な治療法が確立されていない疾患が数多くあります。また、特に異常のない妊娠経過に見えても、胎児期の環境(母体の栄養状態など)が不良の場合、出生後も長期にわたり児の遺伝子発現状態に影響を与えることがわかってきました。さらに、胎児期の環境に起因する長期の影響が成人期にもおよび、生活習慣病等の発症リスクになりうる可能性も指摘されています。そのため、「周産期病態」の研究は成育医療に止まらず、生涯にわたる健康を左右する重要な課題といえます。
これらの背景を踏まえ、本研究部は、周産期に起こる疾患の直接の病因病態を解明すること、そして適切な診断治療法を開発することを目的とします。この目標を達成するために我々は、大きく二つのアプローチで研究に臨んでいます。第一に、実際の症例から頂いた試料(治療の過程で必要とされる採血検査の少量の余剰など)を用い、異常妊娠症例を、特に分子生物学的・遺伝学的手法で解析しています。第二に、異常妊娠症例解析から得られた知見の詳細を再検証するために、培養細胞やモデル動物を用いて解析しています。
これら二つの中核プロジェクトに加え、DNAマイクロアレイ技術や大規模超高速DNA塩基配列解析(次世代シークエンサー)などを積極的に応用し、先進的なヒト異常妊娠の病因病態解明、診断法開発を目指しています。また、国内20カ所以上の医療機関および研究機関と連携して、希少疾患の分子遺伝学的診断情報と研究を進めています。

スタッフ

周産期病態研究部

周産期ゲノミクス研究室

胎児発育研究室

母性管理研究室

部室員

  • 冨川 順子(研究員)
  • 田山 千春(研究員)
  • 漆山 大知
  • 大西 英理子
  • 緒方 広子
  • 加藤 紀子
  • 嘉村 浩美
  • 川崎 範子
  • 久須美 真紀
  • 榊 みずほ
  • 佐藤 泰輔
  • 髙橋 健
  • 髙山 有香
  • 田辺 香子
  • 谷口 公介
  • 右田 王介

業績

2014

  1. Compilation of copy number variants identified in phenotypically normal and parous Japanese women. Migita O, Maehara K, Kamura H, Miyakoshi K, Tanaka M, Morokuma S, Fukushima K, Shimamoto T, Saito S, Sago H, Nishihama K, Abe K, Nakabayashi K, Umezawa A, Okamura K, *Hata K. Journal of Human Genetics. 2014;59:326-331
  2. Comprehensive and quantitative multilocus methylation analysis reveals the susceptibility of specific imprinted differentially methylated regions to aberrant methylation in Beckwith-Wiedemann syndrome with epimutations. Maeda T, Higashimoto K, Jozaki K, Yatsuki H, Nakabayashi K, Makita Y, Tonoki H, Okamoto N, Takada F, Ohashi H, Migita M, Kosaki R, Matsubara K, Ogata T, Matsuo M, Hamasaki Y, Ohtsuka Y, Nishioka K, Joh K, Mukai T, Hata K, Soejima H. Genetics in Medicine. 2014;16:903-912
  3. Wiskott-Aldrich Syndrome in a Girl Caused by Heterozygous WASP Mutation and Extremely Skewed X-Chromosome Inactivation: A Novel Association with Maternal Uniparental Isodisomy 6. Takimoto T, Takada H, Ishimura M, Kirino M, Hata K, Ohara O, Morio T, Hara T. Neonatology. 2015;107:185-190
  4. DNA methylation analysis of human myoblasts during in vitro myogenic differentiation: de novo methylation of promoters of muscle-related genes and its involvement in transcriptional down-regulation. Miyata K, Miyata T, Nakabayashi K, Okamura K, Naito M, Kawai T, Takada S, Kato K, Miyamoto S, Hata K, Asahara H. Human Molecular Genetics. 2015;24:410-423
  5. Paramagnetic Signals in the Globus Pallidus as Late Radiographic Sign of Juvenile-Onset GM1 Gangliosidosis. Takenouchi T, Kosaki R, Nakabayashi K, Hata K, Takahashi T, Kosaki K. Pediatric Neurology. 2014 Oct 16. : S0887-8994(14)00613-4 
  6. The role of maternal-specific H3K9me3 modification in establishing imprinted X-chromosome inactivation and embryogenesis in mice. Fukuda A, Tomikawa J, Miura T, Hata K, Nakabayashi K, Eggan K, Akutsu H, Umezawa A. Nature Communications. 2014;5:5464 
  7. Epimutations of the IG-DMR and the MEG3-DMR at the 14q32.2 imprinted region in two patients with Silver-Russell syndrome-compatible phenotype. Kagami M, Mizuno S, Matsubara K, Nakabayashi K, Sano S, Fuke T, Fukami M, Ogata T. European Journal of Human Genetics. 2014 (in press)
  8. Complete genome sequence of the mitochondrial DNA of the sparkling enope squid, Watasenia scintillans. Hayashi K, Kawai YL, Yura K, Yoshida MA, Ogura A, Hata K, Nakabayashi K, Okamura K. Mitochondrial DNA. 2014 (in press)
  9. Genome-wide copy number analysis and systematic mutation screening in 58 patients with hypogonadotropic hypogonadism. Izumi Y, Suzuki E, Kanzaki S, Yatsuga S, Kinjo S, Igarashi M, Maruyama T, Sano S, Horikawa R, Sato N, Nakabayashi K, Hata K, Umezawa A, Ogata T, Yoshimura Y, Fukami M. Fertility and Sterility. 2014;102:1130-1136
  10. Dynamics of genomic 5-hydroxymethylcytosine during mouse oocyte growth. Sakashita A, Kobayashi H, Wakai T, Sotomaru Y, Hata K, Kono T. Genes to Cells. 2014;19:629-636
  11. Ectopic DNMT3L Triggers Assembly of a Repressive Complex for Retroviral Silencing in Somatic Cells. Kao TH, Liao HF, Wolf D, Tai KY, Chuang CY, Lee HS, Kuo HC, Hata K, Zhang X, Cheng X, Goff SP, Ooi SK, Bestor TH, Lin SP. Journal of Virology. 2014;88:10680-10695 
  12. DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells. Liao HF, Chen WS, Chen YH, Kao TH, Tseng YT, Lee CY, Chiu YC, Lee PL, Lin QJ, Ching YH, Hata K, Cheng WT, Tsai MH, Sasaki H, Ho HN, Wu SC, Huang YH, Yen P, Lin SP. Development. 2014;141:2402-2413
  13. HBx induces hypomethylation of distal intragenic CpG islands required for active expression of developmental regulators. Lee SM, Lee YG, Bae JB, Choi JK, Tayama C, Hata K, Yun Y, Seong JK, Kim YJ. Proceedings of the National Academy of Sciences of the United States of America. 2014;111:9555-9560
  14. Offspring production with sperm grown in vitro from cryopreserved testis tissues. Yokonishi T, Sato T, Komeya M, Katagiri K, Kubota Y, Nakabayashi K, Hata K, Inoue K, Ogonuki N, Ogura A, Ogawa T. Nature Communications. 2014;5:4320
  15. Ataxia telangiectasia derived iPS cells show preserved x-ray sensitivity and decreased chromosomal instability. Fukawatase Y, Toyoda M, Okamura K, Nakamura K, Nakabayashi K, Takada S, Yamazaki-Inoue M, Masuda A, Nasu M, Hata K, Hanaoka K, Higuchi A, Takubo K, Umezawa A. Scientific Reports. 2014;4:5421
  16. The complete type of pachydermoperiostosis: A novel nonsense mutation p.E141* of the SLCO2A1 gene. Niizeki H, Shiohama A, Sasaki T, Seki A, Kabashima K, Otsuka A, Kosaki K, Ogo A, Yamada T, Miyasaka M, Matsuoka K, Hirakiyama A, Okuyama T, Matsuda M, Nakabayashi K, Tanese K, Ishiko A, Amagai M, Kudoh J. Journal of Dermatological Science. 2014;75:193-195
  17. ATF7IP as a novel PDGFRB fusion partner in acute lymphoblastic leukaemia in children. Kobayashi K, Mitsui K, Ichikawa H, Nakabayashi K, Matsuoka M, Kojima Y, Takahashi H, Iijima K, Ootsubo K, Oboki K, Okita H, Yasuda K, Sakamoto H, Hata K, Yoshida T, Matsumoto K, Kiyokawa N, Ohara A. British Journal of Haematology. 2014;165:836-841
  18. Variable maternal methylation overlapping the nc886/vtRNA2-1 locus is locked between hypermethylated repeats and is frequently altered in cancer. Romanelli V, Nakabayashi K, Vizoso M, Moran S, Iglesias-Platas I, Sugahara N, Simón C, Hata K, Esteller M, Court F, Monk D. Epigenetics. 2014;9:783-790
  19. Somatic CTNNB1 mutation in hepatoblastoma from a patient with Simpson-Golabi-Behmel syndrome and germline GPC3 mutation. Kosaki R, Takenouchi T, Takeda N, Kagami M, Nakabayashi K, Hata K, Kosaki K. American Journal of Medical Genetics Part A. 2014;164:993-7
  20. Complete genome sequence of the mitochondrial DNA of the river lamprey, Lethenteron japonicum. Kawai YL, Yura K, Shindo M, Kusakabe R, Hayashi K, Hata K, Nakabayashi K, Okamura K. Mitochondrial DNA. 2014 (in press)
  21. Genome-wide parent-of-origin DNA methylation analysis reveals the intricacies of the human imprintome and suggests a germline methylation independent establishment of imprinting. Court F, Tayama C, Romanelli V, Martin Trujillo A, Iglesias-Platas I, Okamura K, Sugahara N, Simón C, Moore H, Harness JV, Keirstead H, Vicente Sanchez-Mut J, Kaneki E, Lapunzina P, Soejima H, Wake N, Esteller M, Ogata T, Hata K, Nakabayashi K, Monk D. Genome Research. 2014;24:554-569
  22. Compound heterozygous deletions in pseudoautosomal region 1 in an infant with mild manifestations of langer mesomelic dysplasia. Tsuchiya T, Shibata M, Numabe H, Jinno T, Nakabayashi K, Nishimura G, Nagai T, Ogata T, Fukami M. American Journal of Medical Genetics Part A. 2014;164:505-510
  23. De novo Frameshift Mutation in Fibroblast Growth Factor 8 in a Male Patient with Gonadotropin Deficiency. Suzuki E, Yatsuga S, Igarashi M, Miyado M, Nakabayashi K, Hayashi K, Hata K, Umezawa A, Yamada G, Ogata T, Fukami M. Hormone Research in Paediatrics. 2014;81:139-144
  24. Poor responses to tyrosine kinase inhibitors in a child with precursor B-cell acute lymphoblastic leukemia with SNX2-ABL1 chimeric transcript. Masuzawa A, Kiyotani C, Osumi T, Shioda Y, Iijima K, Tomita O, Nakabayashi K, Oboki K, Yasuda K, Sakamoto H, Ichikawa H, Hata K, Yoshida T, Matsumoto K, Kiyokawa N, Mori T. European Journal of Haematology. 2014;92:263-267
  25. Lack of genomic rearrangements involving the aromatase gene CYP19A1 in breast cancer. Fukami M, Suzuki J, Nakabayashi K, Tsunashima R, Ogata T, Shozu M, Noguchi S. Breast Cancer 2014;21:382-385
  26. Aromatase excess syndrome in a family with upstream deletion of CYP19A1. Shihara D, Miyado M, Nakabayashi K, Shozu M, Ogata T, Nagasaki K, Fukami M. Clinical Endocrinology(Oxf) 2014;81:314-316

2013

  1. Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma. Rumbajan JM, Maeda T, Souzaki R, Mitsui K, Higashimoto K, Nakabayashi K, Yatsuki H, Nishioka K, Harada R, Aoki S, Kohashi K, Oda Y, Hata K, Saji T, Taguchi T, Tajiri T, Soejima H, Joh K. BioMed Central Cancer. 2013;13:608
  2. Mutations in SERPINB7, Encoding a Member of the Serine Protease Inhibitor Superfamily, Cause Nagashima-type Palmoplantar Keratosis. Kubo A, Shiohama A, Sasaki T, Nakabayashi K, Kawasaki H, Atsugi T, Sato S, Shimizu A, Mikami S, Tanizaki H, Uchiyama M, Maeda T, Ito T, Sakabe J, Heike T, Okuyama T, Kosaki R, Kosaki K, Kudoh J, Hata K, Umezawa A, Tokura Y, Ishiko A, Niizeki H, Kabashima K, Mitsuhashi Y, Amagai M. The American Journal of Human Genetics. 2013;93:945-956
  3. Fluorescent-Ligand-Mediated Screening of G-Quadruplex Structures Using a DNA Microarray. Iida K, Nakamura T, Yoshida W, Tera M, Nakabayashi K, Hata K, Ikebukuro K, Nagasawa K. Angewandte Chemie International Edition 2013;52:12052-12055
  4. Genomic Basis of Aromatase Excess Syndrome: Recombination- and Replication-Mediated Rearrangements Leading to CYP19A1 Overexpression. Fukami M, Tsuchiya T, Vollbach H, Brown KA, Abe S, Ohtsu S, Wabitsch M, Burger H, Simpson ER, Umezawa A, Shihara D, Nakabayashi K, Bulun SE, Shozu M, Ogata T. The Journal of Clinical Endocrinology & Metabolism. 2013;98:E2013-E2021
  5. DNA methylation contributes to natural human variation. Heyn H, Moran S, Hernando-Herraez I, Sayols S, Gomez A, Sandoval J, Monk D, Hata K, Marques-Bonet T, Wang L, Esteller M. Genome Research. 2013;23:1363-1372
  6. Epigenomics comes of age with expanding roles in biological understanding and clinical application. Kubota T, *Hata K. Journal of Human Genetics. 2013;58:395
  7. Cryptic Genomic Rearrangements in Three Patients with 46, XY Disorders of Sex Development. Igarashi M, Dung VC, Suzuki E, Ida S, Nakacho M, Nakabayashi K, Mizuno K, Hayashi Y, Kohri K, Kojima Y, Ogata T, Fukami M. PLoS One. 2013;8:e68194
  8. Detection of histone modification by chromatin immunoprecipitation combined zinc finger luciferase-based bioluminescence resonance energy transfer assay. Yoshida W, Kezuka A, Abe K, Wakeda H, Nakabayashi K, Hata K, Ikebukuro K. Analytical Chemistry. 2013;85:6485-6490
  9. DNA methylation profile distinguishes clear cell sarcoma of the kidney from other pediatric renal tumors. Ueno H, Okita H, Akimoto S, Kobayashi K, Nakabayashi K, Hata K, Fujimoto J, Hata J, Fukuzawa M, Kiyokawa N. PLoS One. 2013;8:e62233
  10. Epigenetic Regulations in Placentation. Kusumi M, *Hata K. Journal of Mammalian Ova Research. 2013;30:11-15
  11. DNA methyltransferase inhibitor zebularine inhibits human hepatic carcinoma cells proliferation and induces apoptosis. Nakamura K, Aizawa K, Nakabayashi K, Kato N, Yamauchi J, Hata K, Tanoue A. PLoS One. 2013;8:e54036

2012

  1. Development of a Method To Measure DNA Methylation Levels by Using Methyl CpG-Binding Protein and Luciferase-Fused Zinc Finger Protein. Hiraoka D, Yoshida W, Abe K, Wakeda H, Hata K, Ikebukuro K. Anal Chem. 査読有2012;84(19):8259-8264
  2. Characterization of novel paternal ncRNAs at the Plagl1 locus, including Hymai, predicted to interact with regulators of active chromatin. Iglesias-Platas I, Martin-Trujillo A, Cirillo D, Court F, Guillaumet-Adkins A, Camprubi C, Bourc'his D, Hata K, Feil R, Tartaglia G, Arnaud P, Monk D. PLoS One. 査読有2012;7(6):e38907.
  3. Aberrant methylation of H19-DMR acquired after implantation was dissimilar in soma versus placenta of patients with Beckwith-Wiedemann syndrome. Higashimoto K, Nakabayashi K, Yatsuki H, Yoshinaga H, Jozaki K, Okada J, Watanabe Y, Aoki A, Shiozaki A, Saito S, Koide K, Mukai T, Hata K, Soejima H. Am J Med Genet A. 査読有2012;158A(7):1670-5.
  4. Imprinted DNA methylation reprogramming during early mouse embryogenesis at the Gpr1-Zdbf2 locus is linked to long cis-intergenic transcription. Kobayashi H, Sakurai T, Sato S, Nakabayashi K, Hata K, Kono T. FEBS Lett. 査読有2012 23;586(6):827-33. 
  5. Trophoblast-specific DNA methylation occurs after the segregation of the trophectoderm and inner cell mass in the mouse periimplantation embryo. Nakanishi MO, Hayakawa K, Nakabayashi K, Hata K, Shiota K, Tanaka S. Epigenetics.査読有 2012 Feb;7(2):173-82. 
  6. Contribution of intragenic DNA methylation in mouse gametic DNA methylomes to establish oocyte-specific heritable marks. Kobayashi H, Sakurai T, Imai M, Takahashi N, Fukuda A, Yayoi O, Sato S, Nakabayashi K, Hata K, Sotomaru Y, Suzuki Y, Kono T. PLoS Genet. 2012 ;8(1):e1002440.