Narumi, Satoshi

写真a

Affiliation

School of Medicine, Department of Pediatrics (Shinanomachi)

Position

Professor

External Links
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Profile 【 Display / hide 】

  • 2001年慶大医学部卒業。母校の小児科学教室で4年間の臨床研修を行う。2005年から先天性内分泌疾患の分子遺伝学的研究に従事。2009年、慶應義塾大学大学院所定単位取得退学（同年、医学博士号取得）。博士研究員として研究を継続し、2012年には独力で次世代シーケンシング技術を用いた先天性内分泌疾患の包括的遺伝子診断システムを構築。MIRAGE症候群の発見 (Narumi S et al., Nat Genet 2016)などの成果を挙げた。2016年から2023年まで国立成育医療研究センター研究所で室長として活動。2023年から現職。

    日本小児科学会フェロー賞、日本内分泌学会研究奨励賞、日本甲状腺学会七條賞、日本小児内分泌学会学術賞、日本人類遺伝学会奨励賞、慶應医学賞ライジング・スター賞、日本小児科学会学術研究賞など受賞多数。

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Career 【 Display / hide 】

  • 2001.04
    -
    2003.06

    Resident, Keio University Hospital (Department of Pediatrics)

  • 2001.05
    -
    2003.06

    Resident, Keio University Hospital (Department of Pediatrics)

  • 2003.07
    -
    2005.03

    Physician, Department of Pediatrics, Kawasaki Municipal Hospital

  • 2003.07
    -
    2005.06

    Physician, Department of Pediatrics, Kawasaki Municipal Hospital

  • 2009.04
    -
    2016.03

    Instructor, Department of Pediatrics, Keio University School of Medicine

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Academic Background 【 Display / hide 】

  • 2001.03

    Keio University, 医学部

    University, Graduated

  • 2009.11

    Keio University, Medicine, Internal Medicine

    Graduate School, Withdrawal after completion of doctoral course requirements, Doctoral course

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Academic Degrees 【 Display / hide 】

  • Ph.D., Keio University, Coursework, 2009.11

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Research Areas 【 Display / hide 】

  • Life Science / Molecular biology

  • Life Science / Pathological biochemistry

  • Life Science / Embryonic medicine and pediatrics

  • Life Science / Embryonic medicine and pediatrics

  • Life Science / Metabolism and endocrinology

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Research Keywords 【 Display / hide 】

  • MIRAGE症候群

  • Human genetics

  • human genetics

  • Endocrinology

  • 内分泌学

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Research Themes 【 Display / hide 】

  • Genomewide Copy Number Analysis in Patients with Thyroid Dysgenesis, 

    2009
    -
    2011

    　View Summary

    We tested whether copy number variations are involved in etiology of thyroid dysgenesis in this study.

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Papers 【 Display / hide 】

  • Recovery from Atrophic Autoimmune Thyroiditis in a Child: Thyroid Stimulation-Blocking Antibody as a Prognostic Marker.

    Kusano C, Hori N, Hasegawa T, Narumi S

    Hormone research in paediatrics    1 - 5 2025.01

    ISSN  1663-2818

  • Two Novel SLC5A5 Variants (Q263L and G350D) Causing Congenital Hypothyroidism

    Abe K., Koizumi M., Kogai T., Ida S., Sugisawa C., Kawai M., Hasegawa T., Narumi S.

    Thyroid  2025

    ISSN  10507256

    　View Summary

    SLC5A5 encodes sodium-iodide symporter (NIS), which transports inorganic iodide into thyroid cells. Biallelic loss-of-function variants in SLC5A5 cause thyroid dyshormonogenesis due to iodide transport defect (ITD). We report a Japanese sibling with ITD carrying novel compound heterozygous SLC5A5 variants (p. [Gln263Leu]; [Gly350Asp]). The elder brother was diagnosed with congenital hypothyroidism (CH) through newborn screening (NBS), while the younger brother, with a negative NBS result, developed CH-related symptoms at age 3 months. We characterized the two variant NIS proteins in vitro and negligible iodide transport capacity of both proteins. These findings provide unique evidence for the structure-function relationship of the NIS protein.

  • Establishment of Star-edited Y1 cells as a novel in vitro functional assay for STAR

    Takeshi Sato, Satoshi Narumi, Tetsushi Sakuma, Kazuhiro Shimura, Yosuke Ichihashi, Takashi Yamamoto, Tomohiro Ishii, Tomonobu Hasegawa

    Journal of Molecular Endocrinology (Bioscientifica)  73 ( 4 )  2024.11

    ISSN  09525041

    　View Summary

    Genetic variants involving steroidogenic acute regulatory protein cause lipoid congenital adrenal hyperplasia, which is characterized by impaired steroidogenesis in the adrenal glands and gonads. Functional assessment of variant STAR proteins is necessary for accurate genetic diagnosis. Ideally, steroidogenic cells should be used to assess the functionality of STAR proteins, but the presence of endogenous STARs in steroidogenic cells precludes such a method. Here, we generated Star-edited cells from steroidogenic Y1 mouse adrenocortical tumor cells by genome editing. Star-edited Y1 cells exhibited very low but measurable cAMP-dependent pregnenolone production. Furthermore, stimulation of the cAMP pathway for two weeks resulted in the formation of lipid droplets in the cytoplasm of Star-edited Y1 cells, which resembled the histology of the adrenal glands of patients with lipoid congenital adrenal hyperplasia. The steroidogenic defect of Star-edited Y1 cells can be restored by transient over-expression of mouse Star. We found that human STAR can also restore defective steroidogenesis of Star-edited Y1 cells, and were able to construct a novel in vitro system to evaluate human STAR variants. Collectively, we established Star-edited Y1 cells that retain the steroidogenic pathway downstream the Star protein. Star-edited Y1 cells recapitulate the functional and morphological changes of lipoid congenital adrenal hyperplasia, and can be used to evaluate the functionality of human STAR variants.

  • Znrf3 exon 2 deletion mice do not recapitulate congenital adrenal hypoplasia.

    Noboru Uchida, Tomohiro Ishii, Naoko Amano, Shuji Takada, Kyoko Kobayashi, Tomoaki Murakami, Satoshi Narumi, Tomonobu Hasegawa

    Journal of molecular endocrinology 73 ( 4 )  2024.11

    ISSN  09525041

    　View Summary

    Wnt/β-catenin signaling is essential for adrenocortical development. Zinc and ring finger 3 (ZNRF3), an E3 ubiquitin ligase that attenuates Wnt/β-catenin signaling, is negatively regulated by R-spondin via an extracellular domain that is partially encoded by exon 2 of ZNRF3. We recently identified ZNRF3 exon 2 deletions in three individuals with congenital adrenal hypoplasia. ZNRF3 exon 2 deletion impairs R-spondin binding, thereby attenuating β-catenin expression, eventually developing congenital adrenal hypoplasia. To elucidate the influence of ZNRF3/Znrf3 exon 2 deletion on adrenocortical development, we generated homozygous Znrf3 exon 2 deletion (Znrf3Δ2/Δ2) mice. The adrenal glands of Znrf3Δ2/Δ2 mice did not show gross morphological changes at birth but became enlarged with age. Moderate hyperplasia of the zona fasciculata (ZF), dispersed medulla arrangement, and a radially spreading zone comprised of cells with large nuclei between the ZF and medulla were observed at 6 weeks of age. Immunohistochemistry revealed low levels of 20α-hydroxysteroid dehydrogenase, a marker of the adrenal X-zone, in Znrf3Δ2/Δ2 mice. Plasma ACTH and serum corticosterone levels in Znrf3Δ2/Δ2 mice did not differ significantly from those in wild-type mice. Transcriptome analyses of the adrenal glands revealed substantial downregulation of X-zone markers but no significant changes in the expression of genes involved in the Wnt/β-catenin signaling pathway. These results show that a species-specific difference in the effects of ZNRF3/Znrf3 exon 2 deletions in humans and mice; Znrf3Δ2/Δ2 mice do not develop congenital adrenal hypoplasia but instead exhibit moderate ZF hyperplasia, dispersed medulla arrangement, and X-zone dysplasia.

  • Effectiveness of inactivated influenza vaccine in children during the 2023/24 season: The first season after relaxation of intensive COVID-19 measures

    Shinjoh M., Yaginuma M., Yamaguchi Y., Tamura K., Furuichi M., Tsumura Y., Itaki R., Iqbal A., Maeda N., Narabayashi A., Kamei A., Shibata A., Yamada G., Nishida M., Kenichiro T., Chiga M., Shimoyamada M., Yoshida M., Fukushima N., Nakata Y., Fukushima H., Kawakami C., Narumi S., Sugaya N.

    Vaccine 42 ( 23 ) 126241 2024.10

    ISSN  0264410X

    　View Summary

    Background: The annual administration of the influenza vaccine is the most effective method for preventing influenza. We have evaluated the effectiveness of the inactivated influenza vaccine in children aged 6 months to 15 years across the seasons from 2013/2014 to 2022/2023. This study aims to investigate the effectiveness of the inactivated influenza vaccine in the 2023/2024 season, the first year following the easing of strict COVID-19 measures, and possibly the last season when only the inactivated vaccine is available on the market. Methods: Adjusted vaccine effectiveness for the 2023/2024 season was assessed using a test-negative case-control design, with results based on polymerase chain reaction and rapid influenza diagnostic tests. Vaccine effectiveness was calculated by influenza type and patient hospitalization/outpatient status. Results: A total of 1832 children were recruited. The inactivated influenza vaccine was effective in preventing both symptomatic influenza A and B in both inpatient and outpatient settings. Overall vaccine effectiveness for influenza A was 51% (95% confidence interval [CI], 23%–69%, n = 930) in inpatient settings and 54% (95%CI, 27%–71%, n = 559) in outpatient settings. For influenza B, effectiveness was 60% (95%CI, 22%–79%, n = 859) in inpatient settings and 56% (95%CI, 26%–74%, n = 558) in outpatient settings. Analysis suggested that administering two doses enhanced effectiveness specifically against influenza B. Conclusions: This is the first study to demonstrate influenza vaccine effectiveness in children after the relaxation of strict COVID-19 measures in Japan (2023/2024). We recommend the current inactivated vaccine for preventing both influenza A and B in children, with consideration for the potential use of two doses to enhance effectiveness against influenza B.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • 非コード領域に着目した先天性内分泌疾患に関わるゲノム異常の研究

    2023.04
    -
    2027.03

    基盤研究(B), Principal investigator

  • 遺伝子改変マウスを用いたMIRAGE症候群における副腎機能低下症の病態解明

    2021.04
    -
    2024.03

    日本学術振興会, 科学研究費助成事業, 基盤研究(C), No Setting

    　View Summary

    内因性Sf1プロモーター・エンハンサーによりCreリコンビナーゼを発現するマウス（以下Sf1 promoter Creマウス）を九州大学から譲り受けた。Sf1 promoter Creマウスは、マウスSf1遺伝子の５'領域106kb - Creリコンビナーゼ遺伝子- Sf1遺伝子の3’領域100kbを有し、Sf1プロモーターおよび副腎特異的エンハンサーにより副腎皮質にCreリコンビナーゼが強発現する。我々は既に、Creリコンビナーゼにより、ヒト野生型SAMD9遺伝子を発現するマウス（SAMD9-WTマウス）、およびMIRAGE症候群で認めたヒトSAMD9点変異p.R1293Wを発現するマウス（SAMD9-MTマウス）を作成した（平成30年―令和2年度（基盤研究(C)(2)）研究課題番号 18K08527））。今回、SAMD9-WTマウスあるいはSAMD9-MTマウスとSf1 promoter Creマウスを掛け合わせ、胎児期から野生型SAMD9あるいは変異型SAMD9を副腎に強発現する遺伝子改変マウス（それぞれSAMD9-WT副腎発現マウス、およびSAMD9-MT副腎発現マウス）を作成した。SAMD9-WT副腎発現マウス20匹全例は4週齢まで生存し、現在さらに飼育継続中である。一方SAMD9-MT副腎発現マウス9匹のうち6匹は日齢0-1に死亡した。生存中の雌2匹は成獣となり、妊孕性を保持していた。生存中の雄1匹は現在5週齢であるが、同年齢のSAMD9-WT副腎発現マウスに比し、明らかな体重増加不良を示した。日齢0-1に死亡したSAMD9-MT副腎発現マウス3匹の副腎を含む諸臓器をホルマリン固定して保存した。血中ナトリウム、カリウム、糖、ACTH、コルチコステロン測定用にSAMD9-WT副腎発現マウス３匹およびSAMD9-MT副腎発現マウス１匹の血清を保存した。

  • 小児・AYA世代におけるMDSの発生機序と治療戦略の解明

    2021.04
    -
    2024.03

    日本学術振興会, 科学研究費助成事業, 基盤研究(C), No Setting

    　View Summary

    本研究は本邦の小児からAYA世代のMDSの先天性素因の同定と臨床データを合わせて統合解析を行い、発生機序の解明と治療戦略へ繋げる。成人MDSは加齢性変化の影響が大きいが、小児・AYAのMDSは遺伝的要因による造血幹細胞の脆弱性から、感染、炎症による造血ストレス環境、内因性アルデヒド代謝の違いなどにより、骨髄不全の進行と早期のクローン性造血に至ると考えられる。遺伝、環境とも多様な因子があり、未解明な部分が多い。小児科・血液内科・基礎研究を一元的に行い、先天性素因を把握する。令和3年度は症例集積と解析を進めていった。その中で、染色体異常der(1;7)(q10;p10)が、小児、AYA世代の主要な先天性素因であるGATA2異常症においてmonosomy 7に次ぐ特徴であることがわかった。これはドイツ、米国との国際共同研究に加わり、多数例の検討を行った結果であり、そのまま論文発表に至ることができた(Blood.2021;138(23):2441-2445.）。今後とも検討すべき課題はあり、国際共同研究を発展させるべく協力を継続していく。今年度も小児領域、成人領域をまたがる形で、小児科、血液内科との共同研究を開始し、遺伝子解析系とデータベースの構築に努める。また引き続き先天性素因を疑わせる核型異常に注目して、小児、AYA世代のMDS、AML症例を中心に造血転写因子の生殖細胞系列バリアントの解析を開始する。先行解析として20例の当該症例において解析系の構築を進めている。

  • 乳児に発症する炎症性腸疾患と造血不全の原因となる新たな単一遺伝子疾患の確立

    2021.04
    -
    2024.03

    日本学術振興会, 科学研究費助成事業, 基盤研究(C), No Setting

  • Dissecting transcription factors using proximity labeling analyses

    2019.06
    -
    2021.03

    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Narumi Satoshi, Grant-in-Aid for Challenging Research (Exploratory), No Setting

    　View Summary

    Transcriptional regulation is a molecular mechanism that controls the turning on and off of gene functions, but understanding of which molecules are involved in this regulation is lacking. In this study, we employed proximity labeling analysis, a new technique to discover molecular interactions, to analyze transcription factors involved in congenital diseases. As a result, we detected several previously unknown interactions in addition to the previously known ones. This study demonstrates the broad applicability of proximity labeling analysis in the study of transcriptional regulatory mechanisms.

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Awards 【 Display / hide 】

  • 三四会賞（北島賞）

    2024.06, 慶應義塾大学医学部三四会, 先天性内分泌疾患の分子基盤の解明

  • 日本小児内分泌学会　最優秀演題賞

    2023, 日本小児内分泌学会

    Type of Award： Award from Japanese society, conference, symposium, etc.

  • .

    Satoshi Narumi, 2022.04, Japan Pediatric Society, 新規単一遺伝子疾患MIRAGE症候群の発見

  • 日本小児科学会　学術研究賞

    2022, 日本小児科学会

    Type of Award： Award from Japanese society, conference, symposium, etc.

  • 最優秀演題賞

    鳴海 覚志, 2019.10, 日本小児内分泌学会, ゲノムワイド関連解析による甲状腺形成異常感受性SNPの同定

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Courses Taught 【 Display / hide 】

  • PEDIATRICS: SEMINAR

    2024

  • PEDIATRICS: PRACTICE

    2024

  • LECTURE SERIES, PEDIATRICS

    2024

  • DEVELOPMENTAL MEDICINE

    2024

  • CLINICAL CLERKSHIP IN PEDIATRICS

    2024

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Memberships in Academic Societies 【 Display / hide 】

  • 日本甲状腺学会, 

    2009.04
    -
    Present

  • 日本内分泌学会, 

    2005.04
    -
    Present

  • 日本人類遺伝学会, 

    2005.04
    -
    Present

  • 日本小児内分泌学会, 

    2004.04
    -
    Present

  • 日本小児科学会, 

    2001.04
    -
    Present
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Committee Experiences 【 Display / hide 】

  • 2009.04
    -
    Present

    Member, 日本甲状腺学会

  • 2005.04
    -
    Present

    会員, 日本内分泌学会

  • 2005.04
    -
    Present

    会員, 日本人類遺伝学会

    　View Remarks

    2009年-　臨床遺伝専門医

  • 2005.04
    -
    Present

    Member, 日本内分泌学会

  • 2005.04
    -
    Present

    Member, 日本人類遺伝学会

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