Narumi, Satoshi

写真a

Affiliation

School of Medicine, Department of Pediatrics (Shinanomachi)

Position

Professor

External Links

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。

Career 【 Display / hide

  • 2001.05
    -
    2003.06

    Resident, Keio University Hospital (Department of Pediatrics)

  • 2003.07
    -
    2005.06

    Physician, Department of Pediatrics, Kawasaki Municipal Hospital

  • 2009.04
    -
    2016.03

    慶應義塾大学医学部 小児科学 特任助教

  • 2016.04
    -
    2023.03

    国立成育医療研究センター, 分子内分泌研究部, 基礎内分泌研究室長

  • 2023.04
    -
    Present

    慶應義塾大学医学部 小児科学 教授

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

Academic Degrees 【 Display / hide

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

 

Research Areas 【 Display / hide

  • Life Science / Embryonic medicine and pediatrics

Research Keywords 【 Display / hide

  • Human genetics

  • Endocrinology

  • Pediatrics

  • Thyroid

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.

 

Papers 【 Display / hide

  • A Small-for-Gestational-Age Infant with MIRAGE Syndrome Who Developed Heat Stroke and Rhabdomyolysis due to Severe Temperature Instability

    Saito K., Nakagawa R., Narumi S., Ohashi H., Ishiguro A., Kabe K.

    Neonatology (Neonatology)  120 ( 3 ) 390 - 394 2023.07

    ISSN  16617800

     View Summary

    MIRAGE syndrome is characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. This report describes heat stroke and rhabdomyolysis caused by anhidrosis as a symptom of MIRAGE syndrome in a small-for-gestational-age (SGA) female neonate born at 32 weeks of gestation (birth weight, 911 g [-3.8 SD]). She developed severe temperature instability with anhidrosis, growth failure, mild developmental delay, hypothyroidism, and intractable enteropathy. On day 156, her temperature reached 42.0°C; her fever persisted for 2 h with prolonged irritability. Her serum creatine kinase level increased to a peak value of 12,716 (normal range, 43-321) IU/L. The clinical feature was diagnosed as rhabdomyolysis caused by heat stroke, which resulted from physical exertion with anhidrosis. Her SAMD9 variant was c.2945G>A, p. (Arg982His). Neonatologists should be aware of MIRAGE syndrome as a differential diagnosis of SGA with temperature instability.

  • Differential toxicity and localization of arginine-rich C9ORF72 dipeptide repeat proteins depend on de-clustering of positive charges

    Miyagi T., Ueda K., Sugimoto M., Yagi T., Ito D., Yamazaki R., Narumi S., Hayamizu Y., Uji-i H., Kuroda M., Kanekura K.

    iScience (iScience)  26 ( 6 )  2023.06

     View Summary

    Arginine-rich dipeptide repeat proteins (R-DPRs), poly(PR) and poly(GR), translated from the hexanucleotide repeat expansion in the amyotrophic lateral sclerosis (ALS)-causative C9ORF72 gene, contribute significantly to pathogenesis of ALS. Although both R-DPRs share many similarities, there are critical differences in their subcellular localization, phase separation, and toxicity mechanisms. We analyzed localization, protein-protein interactions, and phase separation of R-DPR variants and found that sufficient segregation of arginine charges is necessary for nucleolar distribution. Proline not only efficiently separated the charges, but also allowed for weak, but highly multivalent binding. In contrast, because of its high flexibility, glycine cannot fully separate the charges, and poly(GR) behaves similarly to the contiguous arginines, being trapped in the cytoplasm. We conclude that the amino acid that spaces the arginine charges determines the strength and multivalency of the binding, leading to differences in localization and toxicity mechanisms.

  • Adult Thyroid Outcomes of Congenital Hypothyroidism

    Sugisawa C., Narumi S., Tanase-Nakao K., Hoshiyama A., Suzuki N., Ohye H., Fukushita M., Matsumoto M., Yoshihara A., Watanabe N., Sugino K., Hishinuma A., Noh J.Y., Katoh R., Taniyama M., Ito K.

    Thyroid (Thyroid)  33 ( 5 ) 556 - 565 2023.05

    ISSN  10507256

     View Summary

    Background: More than 40 years have passed since the introduction of newborn screening (NBS) for congenital hypothyroidism (CH), and many early diagnosed patients have reached adulthood. Their thyroid morphology and function have been little studied. This cross-sectional, observational study was conducted to characterize the thyroid morphology and function of adult CH patients diagnosed in the framework of NBS for CH. Methods: A total of 103 adult CH patients born after 1979 were enrolled at Ito Hospital, Tokyo, Japan, and were classified into Goiter, Normal gland, and Dysgenesis groups based on ultrasonographic findings. For 60 patients, genetic analysis was performed. Thyroid function test results and the proportion of patients with thyroid nodules were compared among the three groups and between 56 female CH patients and 168 non-CH women matched for thyrotropin levels. Results: A significantly low serum free triiodothyronine/free thyroxine ratio (0.22) was observed in the Dysgenesis group. Thyroid nodules were detected in 14.3% (8/56) of female CH patients, more frequently than in non-CH women. Thyroid nodules were detected most frequently in the Goiter group (71%, 10/14). Genetic defects were identified in 89% (8/9) of patients belonging to the Goiter group, including thyroglobulin defect (33%, 3/9), thyroid peroxidase defect (33%, 3/9), and dual oxidase 2 defect (22%, 2/9). Conclusions: Our results suggest that adults with thyroid dysgenesis on levothyroxine replacement therapy have relative triiodothyronine deficiency. Most adults with goitrous CH have genetic dyshormonogenesis. They are at high risk of developing thyroid nodules. Our findings support the current guideline recommendation that CH patients with dyshormonogenesis should undergo periodic thyroid ultrasonography.

  • Cord Blood Transplantation in 2 Infants Presenting Monosomy 7 Clonal Hematopoiesis: SAMD9 / SAMD9L Germline Mutation

    Hirai M., Yagasaki H., Kanezawa K., Ueno M., Shimozawa K., Imai K., Morio T., Kato M., Gocho Y., Narumi S., Ebihara Y., Morioka I.

    Journal of Pediatric Hematology/Oncology (Journal of Pediatric Hematology/Oncology)  45 ( 2 ) E290 - E293 2023.03

    ISSN  10774114

     View Summary

    Recently, germline mutations in SAMD9 and SAMD9L were increasingly found in children with monosomy 7. We report the outcomes in 2 infants with the SAMD9/SAMD9L variant, who presented with anemia and thrombocytopenia (patient 1), and neutropenia and nonsymptomatic white-matter-encephalopathy (patient 2). Both patients received cord blood transplantation and experienced critical post-cord blood transplantation adverse events; patients 1 and 2 developed fulminant engraftment syndrome and life-threatening graft-versus-host disease, respectively. Of note, selective loss of chromosome 7 in bone marrow-derived CD34+ cells was inferred.

  • POU1F1/Pou1f1 c.143-83A > G Variant Disrupts the Branch Site in Pre-mRNA and Leads to Dwarfism

    Akiba K., Hasegawa Y., Katoh-Fukui Y., Terao M., Takada S., Hasegawa T., Fukami M., Narumi S.

    Endocrinology (United States) (Endocrinology (United States))  164 ( 2 )  2023.02

    ISSN  00137227

     View Summary

    POU Class 1 Homeobox1 (POU1F1/Pou1f1) is a well-established pituitary-specific transcription factor, and causes, when mutated, combined pituitary hormone deficiency in humans and mice. POU1F1/Pou1f1 has 2 isoforms: the alpha and beta isoforms. Recently, pathogenic variants in the unique coding region of the beta isoform (beta domain) and the intron near the exon-intron boundary for the beta domain were reported, although their functional consequences remain obscure. In this study, we generated mice carrying the Pou1f1 c.143-83A>G substitution that recapitulates the human intronic variant near the exon-intron boundary for the beta domain. Homozygous mice showed postnatal growth failure, with an average body weight that was 35% of wild-type littermates at 12 weeks, which was accompanied by anterior pituitary hypoplasia and deficiency of circulating insulin-like growth factor 1 and thyroxine. The results of RNA-seq analysis of the pituitary gland were consistent with reduction of somatotrophs, and this was confirmed immunohistochemically. Reverse transcription polymerase chain reaction of pituitary Pou1f1 mRNA showed abnormal splicing in homozygous mice, with a decrease in the alpha isoform, an increase in the beta isoform, and the emergence of the exon-skipped transcript. We further characterized artificial variants in or near the beta domain, which were candidate positions of the branch site in pre-mRNA, using cultured cell-basis analysis and found that only c.143-83A>G produced transcripts similar to the mice model. Our report is the first to show that the c.143-83A>G variant leads to splicing disruption and causes morphological and functional abnormalities in the pituitary gland. Furthermore, our mice will contribute understanding the role of POU1F1/Pou1f1 transcripts in pituitary development.

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

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Reviews, Commentaries, etc. 【 Display / hide

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

Awards 【 Display / hide

  • 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.

  • 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.

  • 慶應医学賞 ライジング・スター賞

    2019, 慶應義塾

    Type of Award: Keio commendation etc.

  • 日本小児内分泌学会 最優秀演題賞

    2019, 日本小児内分泌学会

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

  • 日本甲状腺学会 基礎医学研究助成

    2017, 日本甲状腺学会

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

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Courses Taught 【 Display / hide

  • ADVANCED PEDIATRICS

    2023

  • DEVELOPMENTAL MEDICINE

    2023

  • PEDIATRICS: SEMINAR

    2023

  • PEDIATRICS: PRACTICE

    2023

  • 薬理学講義

    2022, Graduate (liberal arts), Lecture

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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

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

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    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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