Narumi, Satoshi

写真a

Affiliation

School of Medicine, Department of Pediatrics (Shinanomachi)

Position

Professor

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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）などの成果を挙げる。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し、15番染色体非コード領域異常による先天性甲状腺機能低下症新規病型の発見（Narumi S et al., Nat Genet 2024）など小児内分泌領域の遺伝診療に関わる基盤的成果を挙げた。2023年からは教授として母校に復帰し、後進の育成に注力している。

    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、三四会賞（北島賞）、小児医学川野賞（基礎医学分野）など受賞多数。

    日本小児科学会認定 小児科専門医・指導医、臨床遺伝専門医制度委員会認定 臨床遺伝専門医、内分泌代謝科専門医（小児科）・指導医

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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 】

  • Influenza vaccination in Japanese children, 2024/25: Effectiveness of inactivated vaccine and limited use of newly introduced live-attenuated vaccine

    Shinjoh M., Tamura K., Yamaguchi Y., Fukushima H., Kuremoto N., Tezuka M., Fukushima N., Yoshida M., Shimoyamada M., Suzuki N., Itaki R., Chiga M., Kobayashi K., Tsunematsu K., Nishida M., Yamada G., Shibata A., Narabayashi A., Kamei A., Maeda N., Tsumura Y., Yaginuma M., Furuichi M., Kawakami C., Narumi S., Sugaya N.

    Vaccine 61   127429 2025.08

    ISSN  0264410X

    　View Summary

    This study evaluated influenza vaccine effectiveness (VE) among children in Japan during the 2024/25 season, when A(H1N1)pdm09 predominated and live-attenuated influenza vaccine (LAIV) was introduced for the first time. Using a test-negative design, febrile children aged 6 months to 15 years were enrolled from 16 hospitals and 2 clinics. Among 1351 participants, LAIV coverage was low (1.2 %), limiting its VE assessment. In contrast, inactivated influenza vaccine (IIV) coverage was 35 %. The adjusted VE of IIV against influenza A was 73 % (95 % CI: 57–83 %) in inpatients and 57 % (24–75 %) in outpatients. VE was significant in younger age groups. A two-dose regimen provided no additional benefit. The effectiveness observed was consistent with previous seasons and global estimates. While the effectiveness of LAIV was unevaluable due to low coverage, IIV remained effective, supporting its continued use in pediatric populations. LAIV effectiveness should be re-evaluated if coverage increases.

  • Clinical and Genetic Characteristics of Adult Nonautoimmune Hypothyroidism: A Single-Institution Study.

    Sugisawa C, Uehara E, Tanase-Nakao K, Inoue K, Iida T, Otsuka F, Suzuki N, Ohye H, Fukushita M, Matsumoto M, Yoshihara A, Watanabe N, Sugino K, Noh JY, Taniyama M, Narumi S, Ito K

    The Journal of clinical endocrinology and metabolism  2025.06

    ISSN  0021-972X

  • Reference Values of Arm Span and Arm Span to Height Ratio of Japanese Population in Childhood and Adolescence: Comparison With Dutch and Turkish Population

    Hirano Y., Inokuchi M., Narumi S., Hasegawa T.

    American Journal of Human Biology 37 ( 4 ) e70051 2025.04

    ISSN  10420533

    　View Summary

    Objectives: To establish age-specific reference values for the arm span and arm span/height ratio of the Japanese population in children and adolescence and elucidate their characteristics compared with those of other populations. Study Design: We analyzed data from a national survey on the body sizes of Japanese people conducted between 1992 and 1994 by the Research Institute of Human Engineering for Quality Life. This study was an observational cross-sectional study, including 6089 boys and 4970 girls aged between 5.5 and 18.5 years. We constructed the reference values and delineated the reference curves for the arm span and arm span/height ratio of the Japanese population in childhood and adolescence using the LMS method. The references were compared with those of the Dutch and Turkish populations using the reference curve of 0 standard deviation. Results: The arm span of the Japanese population increased throughout childhood, with a particularly large increase at the age of puberty. The arm span/height ratio also increased slowly throughout childhood. The Japanese population had a smaller arm span/height ratio than the Dutch and Turkish populations of all ages in childhood and adolescence. Moreover, the arm span/height ratio of the Japanese population reached a constant value at an earlier age than in the Dutch and Turkish populations. Conclusions: We constructed the first reference values for the arm span of Japanese children and adolescents. The Japanese population has shorter arm lengths in relation to their height, and their arm span/height ratio reaches a constant value at an earlier age, compared with the Dutch and Turkish populations.

  • Familial Non-Autoimmune Hyperthyroidism Caused by an Extracellular Domain Variant (p.Leu267Phe) of the TSH Receptor.

    Shimura K, Ichihashi Y, Abe K, Ishii T, Hasegawa T, Narumi S

    Hormone research in paediatrics    1 - 9 2025.02

    ISSN  1663-2818

    　View Summary

    Introduction: Non-autoimmune hyperthyroidism (NAH) is a rare genetic disorder caused by germline-activating variants in the TSH receptor (TSHR) gene. While most NAH-related TSHR variants are located in the seven-transmembrane domain (7TMD), three variants (p.Leu267Phe, p.Ser281Asn, and p.Asn406Ser) have been identified in the extracellular domain (ECD), with p.Leu267Phe previously not showing constitutively active in vitro. Methods: We searched for TSHR variants in a Japanese family with NAH using PCR-based direct sequencing. We created three ECD variants (p.Leu267Phe, p.Ser281Asn, and p.Asn406Ser) and a series of variants in which Leu267 was mutated to 18 amino acids other than Leu and Phe. Based on the cryo-electron microscopic structures, we evaluated the structure-function relationship of TSHR. We compared their cAMP-producing capacities to WT-TSHR in the luciferase activity assay using HEK293 cells. Western blot and fluorescence immunostaining were performed using HA-tagged TSHR vectors to compare Leu267Phe-TSHR with WT-TSHR. Results: A heterozygous TSHR variant (p.Leu267Phe) was identified. Comparison of the cryo-electron microscopy structures of the activated and inactivated TSHRs revealed a significant change in the ECD structure around Leu<sup>267</sup>. The ligand-independent cAMP-producing capacities compared to WT-TSHR were 238 ± 20% (mean ± SEM) for Leu267Phe. Of all 19 possible variants created through systematic mutagenesis, only Leu267Phe-TSHR and Leu267Tyr-TSHR exhibited significantly higher ligand-independent cAMP-producing capacities. Immunoblotting and fluorescence immunostaining showed that the Leu267Phe variant did not affect protein expression levels and intracellular localization of TSHR. Discussion/Conclusion: Leu267Phe-TSHR causes NAH. Substituting Leu<sup>267</sup> to aromatic amino acids may shift the equilibrium of the TSHR state toward activation.

  • 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

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    Introduction: Atrophic autoimmune thyroiditis (AAT) is a form of autoimmune hypothyroidism characterized by the absence of a goiter. Thyroid stimulation-blocking antibody (TSBAb) has been detected in a subset of pediatric AAT cases. Although the disappearance of TSBAb has been related with the recovery of thyroid function in adult AAT cases, similar outcomes have not been documented in pediatric cases. Case Presentation: A 2-year-old Japanese boy presented for evaluation of stunted growth from1 year 10 months of age. Tests for congenital hypothyroidism were negative on newborn screening, and he had no significant medical history. However, he showed symptoms of hypothyroidism (inactiveness, hair loss, dry skin), and primary hypothyroidism was confirmed by blood test (serum TSH level, 818 mU/L; serum free T4 level, <0.40 ng/ dL). The patient exhibited a unique antibody profile: positive for TSH receptor antibody (TRAb) and TSBAb and negative for anti-thyroglobulin antibody (TgAb) and antiperoxidase antibody (TPOAb). He was treated with levothyroxine, after which his growth was normalized. During the 8-year follow-up, the patient's TSBAb levels decreased, allowing for the discontinuation of levothyroxine therapy. Conclusion: We reported the case of a 2-year-old boy diagnosed with AAT who presented with a characteristic antibody profile, negative for TgAb and TPOAb, but positive for TRAb and TSBAb. During 8 years of follow-up, TSBAb seroconversion to negative was observed, leading to treatment discontinuation at age 10 years. This case suggests that monitoring of TSBAb after a diagnosis of AAT may be used to determine treatment discontinuation even in children.

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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 】

  • 小児医学川野賞（基礎医学分野）

    2025.03, 川野小児医学奨学財団, 先天性内分泌疾患の分子病態の解明

    Type of Award： Award from publisher, newspaper, foundation, etc.

  • 小児医学川野賞（基礎医学分野）

    2025.03, 川野小児医学奨学財団, 先天性内分泌疾患の分子病態の解明

  • 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

    Type of Award： Keio commendation etc.

  • 日本小児内分泌学会　最優秀演題賞

    2023.10, 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

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

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Courses Taught 【 Display / hide 】

  • PEDIATRICS: SEMINAR

    2025

  • PEDIATRICS: PRACTICE

    2025

  • LECTURE SERIES, PEDIATRICS

    2025

  • DEVELOPMENTAL MEDICINE

    2025

  • CLINICAL CLERKSHIP IN PEDIATRICS

    2025

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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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