Sugimoto, Shinya

写真a

Affiliation

School of Medicine, The Sakaguchi Laboratory - Department of Organoid Medicine (Shinanomachi)

Position

Assistant Professor (Non-tenured)/Research Associate (Non-tenured)/Instructor (Non-tenured)

Academic Background 【 Display / hide

  • 2003.04
    -
    2009.03

    Keio University, School of Medicine

    University, Graduated

  • 2014.04
    -
    2018.03

    Keio University, 医学研究科医学研究系専攻

    Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide

  • 博士(医学), Keio University, Coursework, 2018.03

    Reconstruction of the Human Colon Epithelium In Vivo

 

Research Areas 【 Display / hide

  • Gastroenterology

Research Keywords 【 Display / hide

  • オルガノイド

  • 炎症性腸疾患

  • 腸管上皮幹細胞

 

Papers 【 Display / hide

  • Direct derivation of human alveolospheres for SARS-CoV-2 infection modeling and drug screening.

    Ebisudani T, Sugimoto S, Haga K, Mitsuishi A, Takai-Todaka R, Fujii M, Toshimitsu K, Hamamoto J, Sugihara K, Hishida T, Asamura H, Fukunaga K, Yasuda H, Katayama K, Sato T

    Cell reports 35 ( 10 ) 109218 2021.06

  • Demarcated redness associated with increased vascular density/size: a useful marker of flat-type dysplasia in patients with ulcerative colitis.

    Ikebata A, Shimoda M, Okabayashi K, Uraoka T, Maehata T, Sugimoto S, Mutaguchi M, Naganuma M, Kameyama K, Yahagi N, Kanai T, Kitagawa Y, Kanai Y, Iwao Y

    Endoscopy international open 9 ( 4 ) E552 - E561 2021.04

    ISSN  2364-3722

  • An organoid-based organ-repurposing approach to treat short bowel syndrome.

    Sugimoto S, Kobayashi E, Fujii M, Ohta Y, Arai K, Matano M, Ishikawa K, Miyamoto K, Toshimitsu K, Takahashi S, Nanki K, Hakamata Y, Kanai T, Sato T

    Nature (Nature)  592 ( 7852 ) 99 - 104 2021.02

    ISSN  0028-0836

     View Summary

    The small intestine is the main organ for nutrient absorption, and its extensive resection leads to malabsorption and wasting conditions referred to as short bowel syndrome (SBS). Organoid technology enables an efficient expansion of intestinal epithelium tissue in vitro , but reconstruction of the whole small intestine, including the complex lymphovascular system, has remained challenging . Here we generate a functional small intestinalized colon (SIC) by replacing the native colonic epithelium with ileum-derived organoids. We first find that xenotransplanted human ileum organoids maintain their regional identity and form nascent villus structures in the mouse colon. In vitro culture of an organoid monolayer further reveals an essential role for luminal mechanistic flow in the formation of villi. We then develop a rat SIC model by repositioning the SIC at the ileocaecal junction, where the epithelium is exposed to a constant luminal stream of intestinal juice. This anatomical relocation provides the SIC with organ structures of the small intestine, including intact vasculature and innervation, villous structures, and the lacteal (a fat-absorbing lymphatic structure specific to the small intestine). The SIC has absorptive functions and markedly ameliorates intestinal failure in a rat model of SBS, whereas transplantation of colon organoids instead of ileum organoids invariably leads to mortality. These data provide a proof of principle for the use of intestinal organoids for regenerative purposes, and offer a feasible strategy for SBS treatment. 1 2

  • Wnt Signaling Shapes the Histologic Variation in Diffuse Gastric Cancer.

    Togasaki K, Sugimoto S, Ohta Y, Nanki K, Matano M, Takahashi S, Fujii M, Kanai T, Sato T

    Gastroenterology (Gastroenterology)  160 ( 3 ) 823 - 830 2021.02

    ISSN  0016-5085

     View Summary

    Background and Aims: Diffuse-type gastric cancer (GC) is currently subdivided into signet-ring cell carcinoma (SRCC) and non-SRCC, referred to as poorly cohesive carcinoma not otherwise specified (PCC-NOS). Although these subtypes are considered to be independent, they often coexist in the same tumors, raising a question of whether they clonally differ or not. To tackle this question, we established an experimental platform for human diffuse GC that enables accurate modeling of histologic subtypes. Methods: Seven patient-derived diffuse GC organoid lines were established, characterized by histopathologic analysis, in situ hybridization, and gene expression analysis. For genetic modeling of diffuse GC, we knocked out CDH1 and/or TP53 in human normal gastric organoids. Green fluorescent protein–labeled GC organoids were xenotransplanted into immune-deficient mice for in vivo assessment. Results: PCC-NOS organoids transformed into SRCC-like structures on removal of Wnt and R-spondin from the culture medium. This morphologic change paralleled downregulation of Wnt-target and gastric stem cell genes, including LGR5, and elevation of differentiation markers, such as KRT20 and MUCs. The association between Wnt target gene expression and histologic subtypes was confirmed in 3 patient-derived GC tissues. In vivo, single clone-derived organoids formed tumors that comprised 2 distinct histologic compartments, each corresponding to SRCC and PCC-NOS. The transition from PCC-NOS to SRCC histology reflected the abundance of surrounding R-spondin–expressing fibroblasts. Conclusions: SRCC and PCC-NOS were clonally identical, and their morphology was regulated by extracellular Wnt and R-spondin expression. Our results decoded how genetic mutations and the tumor environment shape pathohistologic and biologic phenotypes in human diffuse GCs.

  • An Organoid Biobank of Neuroendocrine Neoplasms Enables Genotype-Phenotype Mapping.

    Kawasaki K, Toshimitsu K, Matano M, Fujita M, Fujii M, Togasaki K, Ebisudani T, Shimokawa M, Takano A, Takahashi S, Ohta Y, Nanki K, Igarashi R, Ishimaru K, Ishida H, Sukawa Y, Sugimoto S, Saito Y, Maejima K, Sasagawa S, Lee H, Kim HG, Ha K, Hamamoto J, Fukunaga K, Maekawa A, Tanabe M, Ishihara S, Hamamoto Y, Yasuda H, Sekine S, Kudo A, Kitagawa Y, Kanai T, Nakagawa H, Sato T

    Cell (Cell)  183 ( 5 ) 1420 - 1435.e21 2020.10

    ISSN  0092-8674

     View Summary

    © 2020 Elsevier Inc. Gastroenteropancreatic (GEP) neuroendocrine neoplasm (NEN) that consists of neuroendocrine tumor and neuroendocrine carcinoma (NEC) is a lethal but under-investigated disease owing to its rarity. To fill the scarcity of clinically relevant models of GEP-NEN, we here established 25 lines of NEN organoids and performed their comprehensive molecular characterization. GEP-NEN organoids recapitulated pathohistological and functional phenotypes of the original tumors. Whole-genome sequencing revealed frequent genetic alterations in TP53 and RB1 in GEP-NECs, and characteristic chromosome-wide loss of heterozygosity in GEP-NENs. Transcriptome analysis identified molecular subtypes that are distinguished by the expression of distinct transcription factors. GEP-NEN organoids gained independence from the stem cell niche irrespective of genetic mutations. Compound knockout of TP53 and RB1, together with overexpression of key transcription factors, conferred on the normal colonic epithelium phenotypes that are compatible with GEP-NEN biology. Altogether, our study not only provides genetic understanding of GEP-NEN, but also connects its genetics and biological phenotypes. Gastroenteropancreatic neuroendocrine neoplasms are a rare but lethal cancer with a scarcity of clinically relevant models. Kawasaki et al. establish and characterize 25 organoid lines to identify molecular subtypes with genotype-phenotype mapping.

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Reviews, Commentaries, etc. 【 Display / hide

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

  • 短腸症候群モデルを用いた新規移植療法の開発

    2021.07
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 杉本 真也, Grant-in-Aid for Challenging Research (Exploratory), Principal Investigator

  • Functional analysis of small intestinal epithelial organoid-based transplant graft

    2020.04
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 杉本 真也, Grant-in-Aid for Scientific Research (B), Principal Investigator

  • 腸管AhRワールドの解明

    2019.02
    -
    2021.03

    文部科学省・日本学術振興会, 科学研究費助成事業, 金井 隆典, Promotion of Joint International Research (Fostering Joint International Research (B)), Co-investigator

  • 腸管上皮-間質ニッチの包括的理解と自己補完的組織培養技術の確立

    2015.04
    -
    2018.03

    文部科学省・日本学術振興会, 科学研究費助成事業, 杉本 真也, 特別研究員奨励費, Principal Investigator

Awards 【 Display / hide

  • 日本再生医療学会奨励賞(基礎部門)

    2021.03

    Type of Award: Awards of National Conference, Council and Symposium

  • 若手奨励賞

    2019.11, JDDW

    Type of Award: Awards of National Conference, Council and Symposium

  • Medical Research Encouragement Prize of the Tokyo Medical Association

    2019.03, The Tokyo Medical Association

    Type of Award: Awards of Publisher, Newspaper Company and Foundation

  • Inoue Research Award for Young Scientists

    2019.02, Inoue Foundation for Science

    Type of Award: Awards of Publisher, Newspaper Company and Foundation

  • Young Investigator Award

    2018.06, Keio University School of Medicine Alumni Association

    Type of Award: Keio commendation etc.

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