Updated on 2024/12/20

Information

 

写真a

 
KITAJIMA KEIKO
 
Organization
Faculty of Medical Sciences Department of Basic Medicine Assistant Professor
School of Medicine Department of Medicine(Concurrent)
Title
Assistant Professor
Profile
Research for axes formation between development, using techniques of Developmental and Molecular Biology
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Research Areas

  • Life Science / Developmental biology

  • Life Science / Molecular biology

Degree

  • Doctor of Philosophy

Research History

  • - Kyushu University, Assistant Professor

    2006

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  • - 九州大学大学院医学研究院 助手

    2006

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  • Osaka University Faculty of Medicine

    2000

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  • 島根大学医学部、2000年9月〜2006年3月

Education

  • Osaka University

    - 2000

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  • Osaka University

    - 2000

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    Country: Japan

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  • Shimane University

    - 1994

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    Country: Japan

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  • Shimane University   Faculty of Agriculture

    - 1994

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Research Interests・Research Keywords

  • Research theme:発生生物学

    Keyword:発生生物学

    Research period: 2024

  • Research theme:分子生物学

    Keyword:分子生物学

    Research period: 2024

  • Research theme:Developmental Biology

    Keyword:Developmental Biology

    Research period: 2024

  • Research theme:Molecular mechanisms of body axis formation

    Keyword:mouse, development, body axes

    Research period: 2006.4

Papers

  • Wnt signaling regulates left-right axis formation in the node of mouse embryos. Reviewed International journal

    Developmental Biology   380 ( 2 )   222 - 232   2013.8

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

    DOI: 10.1016/j.ydbio.2013.05.011

  • Dissecting the role of Fgf signaling during gastrulation and left-right axis formation in mouse embryos using chemical inhibitors. Reviewed International journal

    Oki S, Kitajima K, Meno C.

    Developmental Dynamics   239 ( 6 )   2010.6

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

    DOI: 10.1002/dvdy.22282

  • Reversal of left-right asymmetry induced by aberrant Nodal signaling in the node of mouse embryos. Reviewed International journal

    Oki S., Kitajima K., Marques S., Belo JA., Yokoyama T., Hamada H., Meno C.

    Development   136 ( 23 )   2009.12

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

  • Hyperglycaemia induces diet-dependent defects of the left-right axis by lowering intracellular pH

    Matsuoka, R; Kitajima, K; Nii, T; Zou, ZA; Tanaka, K; Joo, K; Ohkawa, Y; Ohga, S; Meno, C

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE   1871 ( 1 )   167550   2025.1   ISSN:0925-4439 eISSN:1879-260X

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    Language:English   Publisher:Biochimica et Biophysica Acta - Molecular Basis of Disease  

    Pregestational diabetes is a risk factor for congenital anomalies, including heterotaxy syndrome, a rare birth defect characterized by the abnormal arrangement of organs relative to the left-right (L-R) body axis. To provide insight into the underlying mechanism by which diabetes induces heterotaxy, we here analyzed the L-R axis of mouse embryos of diabetic dams. Various Pitx2 expression patterns indicative of disruption of L-R axis formation were apparent in such embryos. Expression of Nodal at the node, which triggers a Nodal-Pitx2 expression cascade in lateral plate mesoderm, showed marked regression associated with L-R axis malformation. This regression was similar to that apparent in Wnt3a−/− embryos, and canonical Wnt signalling was indeed found to be downregulated in embryos of diabetic dams. RNA sequencing revealed dysregulation of glycolysis in embryos of diabetic dams, and high glucose lowered intracellular pH in the primitive streak, leading to the suppression of Wnt signalling and the regression of Nodal expression. Of note, maternal vitamin A intake increased the incidence of L-R axis defects in embryos of diabetic dams, with dysregulation of retinoic acid metabolism being apparent in these embryos and in Wnt3a−/− embryos. Our results shed light on the mechanisms underlying embryopathies associated with maternal diabetes and suggest the importance of diet for prevention of heterotaxy.

    DOI: 10.1016/j.bbadis.2024.167550

    Web of Science

    Scopus

    PubMed

  • Expression of leukotriene B4 receptor 1 defines functionally distinct DCs that control allergic skin inflammation Reviewed International journal

    Tomoaki Koga, Fumiyuki Sasaki, Kazuko Saeki, Soken Tsuchiya, Toshiaki Okuno, Mai Ohba, Takako Ichiki, Satoshi Iwamoto, Hirotsugu Uzawa, Keiko Kitajima, Chikara Meno, Eri Nakamura, Norihiro Tada, Yoshinori Fukui, Junichi Kikuta, Masaru Ishii, Yukihiko Sugimoto, Mitsuyoshi Nakao, Takehiko Yokomizo

    Cell Mol Immunol.   2020.10

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

    DOI: 10.1038/s41423-020-00559-7

  • Endocardium differentiation through Sox17 expression in endocardium precursor cells regulates heart development in mice Reviewed

    Rie Saba, Keiko Kitajima, Lucille Rainbow, Silvia Engert, Mami Uemura, Hidekazu Ishida, Ioannis Kokkinopoulos, Yasunori Shintani, Shigeru Miyagawa, Yoshiakira Kanai, Masami Kanai-Azuma, Peter Koopman, Chikara Meno, John Kenny, Heiko Lickert, Yumiko Saga, Ken Suzuki, Yoshiki Sawa, Kenta Yashiro

    Scientific reports   9 ( 1 )   2019.12

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

    DOI: 10.1038/s41598-019-48321-y

  • Leukotriene B4 receptor type 2 (BLT2) enhances skin barrier function by regulating tight junction proteins. Reviewed International journal

    30 ( 2 )   933 - 947   2016.2

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

    DOI: 10.1096/fj

  • Hyperglycemia impairs left-right axis formation and thereby disturbs heart morphogenesis in mouse embryos. Reviewed International journal

    112 ( .8 )   E5300 - E5307   2015.10

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

    DOI: 10.1073/pnas.

  • Epiblast ground state is controlled by canonical Wnt/β-catenin signaling in the postimplantation mouse embryo and epiblast stem cells. Reviewed International journal

    角 智行, 沖 真弥, 北島 桂子, 目野 主税

    8 ( 5 )   e63378   2013.5

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

    Epiblast stem cells (EpiSCs) are primed pluripotent stem cells and can be derived from postimplantation mouse embryos. We now show that the absence of canonical Wnt/β-catenin signaling is essential for maintenance of the undifferentiated state in mouse EpiSCs and in the epiblast of mouse embryos. Attenuation of Wnt signaling with the small-molecule inhibitor XAV939 or deletion of the β-catenin gene blocked spontaneous differentiation of EpiSCs toward mesoderm and enhanced the expression of pluripotency factor genes, allowing propagation of EpiSCs as a homogeneous population. EpiSCs were efficiently established and propagated from single epiblast cells in the presence of both XAV939 and the Rho kinase (ROCK) inhibitor Y27632. Cell transplantation revealed that EpiSCs were able to contribute to primordial germ cells and descendants of all three germ layers in a host embryo, suggesting that they maintained pluripotency, even after prolonged culture with XAV939. Such an improvement in the homogeneity of pluripotency achieved with the use of a Wnt inhibitor should prove advantageous for manipulation of primed pluripotent stem cells.

    DOI: 10.1371/journal.pone.0063378

  • Restriction of Wnt signaling in the dorsal otocyst determines semicircular canal formation in the mouse embryo. Reviewed International journal

    Noda T, Oki S, Kitajima K, Harada T, Komune S, Meno C.

    Developmental Biology   362 ( 1 )   2012.2

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

  • DOCK180 is a Rac activator that regulates cardiovascular development by acting downstream of CXCR4. Reviewed International journal

    Circulation Research   107 ( 9 )   2010.9

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

    DOI: 10.1161/CIRCRESAHA.110.223388

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Presentations

  • Wnt signaling regulates the left-right axis formation in the node International conference

    MOUSE MOLECULAR GENETICS  2013.9 

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    Event date: 2013.9

    Language:English   Presentation type:Symposium, workshop panel (public)  

    Country:United Kingdom  

  • Wnt signaling regulates the left-right axis formation in the node of mouse embryos International conference

    46th Annual Meeting of JSDB  2013.5 

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    Event date: 2013.5

    Language:English  

    Country:Japan  

  • 母体高血糖による細胞内pH低下が食餌依存性の胎児左右軸異常を誘導する

    松岡良平、北島桂子、大賀正一、目野主税

    日本心臓血管発生研究会  2023.12 

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    Event date: 2023.12

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:淡路夢舞台国際会議場   Country:Japan  

  • 糖尿病合併妊娠における栄養素摂取と胎児先天異常との関連性の解析

    #鄒 兆南, @北島 桂子, @本田 瑞季, @目野 主税

    第42回日本分子生物学会年会  2019.12 

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    Event date: 2019.12

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:福岡国際会議場・マリンメッセ福岡   Country:Japan  

  • Sox17 expression in the endocardium precursor cells regulates the mouse heart development International conference

    Rie Saba, Keiko Kitajima, Yasuinori Shintani, Yoshiakira Kanai, Masami Kanai-Azuma, Chikara Meno, Rumiko Saga, Ken Suzuki, Shigeru Miyagawa, Yoshiki Sawa, Hideya Yamazaki, Kei Yamada, Kenta Yasuhiro

    2019.12 

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    Event date: 2019.12

    Language:English  

    Country:Japan  

  • 高血糖がマウス胚の 左右軸形成に及ぼす影響

    @目野 主税, @蜂須賀 正紘, #鄒 兆南, @沖 真弥, @北島 桂子

    第41回日本分子生物学会年会  2018.11 

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    Event date: 2018.11

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:パシフィコ横浜   Country:Japan  

  • 母体糖尿病における内臓錯位発症のメカニズムの解析

    #鄒 兆南, @北島 桂子, @目野 主税

    第41回日本分子生物学会年会  2018.11 

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    Event date: 2018.11

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:パシフィコ横浜   Country:Japan  

  • 高血糖がマウス胚の左右軸形成に及ぼす影響

    目野主税、蜂須賀正紘、鄒兆南、沖真弥、北島桂子

    2017.8 

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    Event date: 2017.8

    Language:Japanese  

    Country:Japan  

  • 高血糖症はマウス胚の左右軸形成を阻害することで心臓形態形成を撹乱する

    北島 桂子, 沖 真弥, 目野 主税, 角 智行

    日本分子生物学会  2014.11 

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    Event date: 2014.11

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:パシフィコ横浜   Country:Japan  

    先天性心疾患はヒトで最も頻発する先天異常の一つであり、最近の研究によると新生児の罹患率は約1%である。先天性心疾患は必ずしも遺伝学的な異常によって起こるものではなく、様々な環境要因が特定の先天性心疾患の発生リスクを高めることが疫学調査から明らかになっている。妊娠前糖尿病はそのような環境要因の一つである。妊娠前糖尿病に関連した先天性心疾患に特徴的なのは、これに内臓錯位を伴うケースが存在することである。しかしながら、高血糖症によって先天性心疾患が引き起こされる仕組みは、臨床的にも重要な問題であるにも関わらず、ほとんど明らかになっていない。 臓器の左右非対称性は発生初期に確立される左右軸に基づいて形成される。糖尿病に関連して心疾患及び内臓錯位が発生する分子機構を解明するため、ストレプトゾシンによる糖尿病雌マウスに由来する胚、及び高濃度グルコース培地で培養したマウス胚における左右軸形成を解析した。その結果、高濃度グルコースは心臓形態形成に必要な左右軸の確立を撹乱することが明らかになった。この年会では、最新のデータを提示すると共に、妊娠前糖尿病に関連した先天性心疾患の発生機序について話したい。

  • マウス胚の左右軸決定におけるWntシグナル経路の機能解析

    北島 桂子, 角 智行, 沖 真弥, 目野 主税

    生医研リトリート2013  2013.8 

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    Event date: 2013.8

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:ホテルセキア   Country:Japan  

    The node triggers formation of the left-right axis in mouse embryos by establishing local asymmetry of Nodal and Cerl2 expression. We found that Wnt3 is expressed in perinodal crown cells preferentially on the left side. The enhancer responsible for Wnt3 expression was identified and found to be regulated by Foxa2 and Rbpj under the control of Notch signaling. Rbpj binding sites suppress enhancer activity in pit cells of the node, thereby ensuring crown cell–specific expression. In addition, we found that the expression of Gdf1 and Cerl2 is also regulated by Notch signaling, suggesting that such signaling may induce the expression of genes related to left-right asymmetry as a set. Furthermore, Cerl2 expression became symmetric in response to inhibition of Wnt–β-catenin signaling. Our results suggest that Wnt signaling regulates the asymmetry of Cerl2 expression, which likely generates a left-right difference in Nodal activity at the node for further amplification in lateral plate mesoderm.

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Professional Memberships

Research Projects

  • 胎児の左右軸形成異常を引き起こす糖尿病母胎環境と分子メカニズムの解析

    Grant number:22K07871  2022 - 2024

    日本学術振興会  科学研究費助成事業  基盤研究(C)

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • Molecular mechanisms of the fetal left-right axis malformations induced by maternal hyperglycemia.

    Grant number:18K07880  2018 - 2020

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Kitajima Keiko

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    Authorship:Principal investigator  Grant type:Scientific research funding

    The expression of Nodal and Cerl2 was decreased in the node of 8.0-day embryo exposed to high glucose concentration, and it was due to the reduction of active form of NOTCH (NICD) in the node. We focused on Wnt3a which is required for the expression of NOTCH around the node in 8.0-day embryo, and identified two enhancers, PSE1 and PSE2, for primitive streak specific expression of Wnt3a. We first introduced point mutation in Wnt3a PSE1 by CRISPR/Cas9 system, but there was no significant decrease in expression of Wnt3a in the pimitive streak, and the obtained homozygote pups were viable.

    CiNii Research

  • 糖尿病で生じる胎児の左右軸形態異常の分子機構解析

    Grant number:26461637  2014 - 2017

    日本学術振興会  科学研究費助成事業  基盤研究(C)

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    Authorship:Principal investigator  Grant type:Scientific research funding

Class subject

  • 人体発生学

    2023.10 - 2024.3   Second semester

  • 人体発生学

    2022.10 - 2023.3   Second semester

  • 人体発生学

    2021.10 - 2022.3   Second semester

  • 人体発生学

    2020.10 - 2021.3   Second semester

  • 人体発生学

    2019.10 - 2020.3   Second semester

  • 人体発生学

    2018.10 - 2019.3   Second semester

  • 人体発生学

    2017.10 - 2018.3   Second semester

  • 人体発生学

    2016.10 - 2017.3   Second semester

  • 人体発生学

    2015.10 - 2016.3   Second semester

  • 人体発生学

    2014.10 - 2015.3   Second semester

  • 人体発生学

    2013.10 - 2014.3   Second semester

  • 人体発生学

    2012.10 - 2013.3   Second semester

  • 人体発生学

    2011.10 - 2012.3   Second semester

  • 生物科学I

    2010.10 - 2011.3   Second semester

  • 人体発生学

    2010.10 - 2011.3   Second semester

  • 人体発生学

    2009.10 - 2010.3   Second semester

  • 基礎配属実習

    2009.4 - 2009.9   First semester

  • 人体発生学

    2008.10 - 2009.3   Second semester

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Outline of Social Contribution and International Cooperation activities

  • Queen Mary University of Londonの八代健太博士との共同研究「単一細胞発現プロファイル解析によって得られた心筋前駆細胞に関する新知見」の連携研究者として共同研究を行っている。

Social Activities

  • 馬出オープンキャンパス 高校生に対する九州大学医学部の紹介

    2019.8

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    Audience: Infants, Schoolchildren, Junior students, High school students

    Type:Seminar, workshop

  • 馬出オープンキャンパス 高校生に対する九州大学医学部の紹介

    2018.8

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    Audience: Infants, Schoolchildren, Junior students, High school students

    Type:Seminar, workshop

  • 馬出オープンキャンパス 高校生に対する九州大学医学部の紹介

    2017.8

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    Audience: Infants, Schoolchildren, Junior students, High school students

    Type:Seminar, workshop

  • 馬出オープンキャンパス 高校生に対する九州大学医学部の紹介

    2016.8

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    Audience: Infants, Schoolchildren, Junior students, High school students

    Type:Seminar, workshop

  • 馬出オープンキャンパス 高校生に対する九州大学医学部の紹介

    2015.8

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    Audience: Infants, Schoolchildren, Junior students, High school students

    Type:Seminar, workshop

  • 馬出オープンキャンパス 高校生に対する九州大学医学部の紹介

    2014.8

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    Audience: Infants, Schoolchildren, Junior students, High school students

    Type:Seminar, workshop

  • 馬出オープンキャンパス 高校生に対する九州大学医学部の紹介

    2013.8

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    Audience: Infants, Schoolchildren, Junior students, High school students

    Type:Seminar, workshop

  • 馬出オープンキャンパス 高校生に対する九州大学医学部の紹介

    2012.8

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    Audience: Infants, Schoolchildren, Junior students, High school students

    Type:Seminar, workshop

  • 馬出オープンキャンパス 高校生に対する九州大学医学部の紹介

    2011.8

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    Audience: Infants, Schoolchildren, Junior students, High school students

    Type:Seminar, workshop

  • 馬出オープンキャンパス 高校生に対する九州大学医学部の紹介

    2011.8

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    Type:Science cafe

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