Saito, Yoshimasa

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmacy 薬物治療学講座 (Shiba-Kyoritsu)

Position

Professor

 

Research Areas 【 Display / hide

  • Tumor diagnostics

  • Tumor therapeutics

 

Books 【 Display / hide

  • 遺伝子診断と個別化医療.「ゲノム創薬科学」

    Saito Yoshimasa, 裳華房, 2017.10

    Scope: pp269-287

  • エピジェネティクスとアンチエイジング医学.「アンチエイジング医学の基礎と臨床」第3版.

    齋藤 義正, メジカルビュー社, 東京, 2015.09

    Scope: pp42-44

  • Advanced Glycation End-products (AGEs)阻害薬がOLEFTラットの肝および脂肪組織に及ぼす影響. 「酸化ストレスと肝疾患 8巻」.

    木村真規、南雲まい、飯田陽子、山田華名、齋藤義正、齋藤英胤., 株式会社嵯峨野, 東京, 2012.09

    Scope: pp67-72

  • 加齢と消化器系の変化.「高齢者用食品の開発と展望」.

    齋藤義正、齋藤英胤., シーエムシー出版, 東京, 2012.07

    Scope: pp7-12

Papers 【 Display / hide

  • Building consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids.

    Marsee A, Roos FJM, Verstegen MMA; HPB Organoid Consortium, Gehart H, de Koning E, Lemaigre F, Forbes SJ, Peng WC, Huch M, Takebe T, Vallier L, Clevers H, van der Laan LJW, Spee B.

    Cell Stem Cell 28 ( 5 ) 816 - 832 2021.05

    Research paper (scientific journal), Joint Work, Accepted

  • The effects of continuous and withdrawal voluntary wheel running exercise on the expression of senescence-related genes in the visceral adipose tissue of young mice

    Kimura M., Suzuki S., Moriya A., Nogami K., Uchida R., Saito Y., Saito H.

    International Journal of Molecular Sciences (International Journal of Molecular Sciences)  22 ( 1 ) 1 - 12 2021.01

    ISSN  16616596

     View Summary

    © 2020 by the authors. Obesity has become a global medical problem. The upregulation of senescence-related markers in adipose tissue may cause impairment of adipose tissue and disorders of systemic me-tabolism. Weight control through diet has been found to ameliorate senescence in the adipose tissue. Exercise is also important in maintaining a healthy lifestyle, however, very few researchers have examined the relationship between senescence-related markers in adipose tissue. Dietary restriction is also reported to have a legacy effect, wherein the effects are maintained for some periods after the termination of the intervention. However, very few researchers have examined the relationship between exercise and senescence-related markers in adipose tissue. Besides, there is no study on the long-term effects of exercise. Hence, we investigated whether the exercise could change the expression of senescence-related genes in the visceral adipose tissue of young mice and whether there was a legacy effect of exercise for 10 weeks after the termination of exercise. Four-week-old male ICR mice were assigned to one of the three groups: 20 weeks of sedentary condition, 20 weeks of voluntary wheel running exercise, or 10 weeks of exercise followed by 10 weeks of sedentary condition. The mice showed decreased expression in genes related to senescence and senescence-associated secretory phenotype, such as p53, p16, and IL-6, in the visceral adipose tissue in response to exercise. These effects were maintained for 10 weeks after the mice stopped exercising. Our study is the first report that exercise reduces the expression of senescence-related genes in the visceral adipose tissue of young mice, and that exercise causes the legacy effect.

  • 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 H.G., 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 2020.11

    ISSN  00928674

     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.

  • Establishment and Long-Term Culture of Organoids Derived from Human Biliary Tract Carcinoma.

    Saito Y, Muramatsu T, Saito H.

    STAR Protocols 1 ( 1 ) 100009 2020.06

    Research paper (scientific journal), Joint Work, Accepted

  • Epigenetic silencing of Lgr5 induces senescence of intestinal epithelial organoids during the process of aging

    Uchida R., Saito Y., Nogami K., Kajiyama Y., Suzuki Y., Kawase Y., Nakaoka T., Muramatsu T., Kimura M., Saito H.

    npj Aging and Mechanisms of Disease (npj Aging and Mechanisms of Disease)  5 ( 1 )  2019.12

     View Summary

    © 2018, The Author(s). To understand the molecular features underlying stem cell aging, we established intestinal epithelial organoids derived from both young and aged mice and investigated alterations in their senescence and epigenetic status. Senescence-related changes including accumulation of senescence-associated β-galactosidase and up-regulation of Cdkn1a (p21) by DNA demethylation were observed in intestinal epithelial organoids derived from aged mice. We also demonstrated that the important stem cell marker Lgr5 was epigenetically silenced by trimethylation of histone H3 lysine 27, inducing suppression of Wnt signaling and a decrease of cell proliferation in organoids from aged mice. We further treated intestinal epithelial organoids from aged mice with nicotinamide mononucleotide (NMN), a key NAD + intermediate. As a result, the organoids showed a higher NAD + level, increased cell proliferative ability, activation of Lgr5 and suppression of senescence-associated genes, indicating that treatment with NMN could ameliorate senescence-related changes in intestinal epithelia. These findings suggest that organoids derived from aged animals could be a powerful research tool for investigating the molecular mechanisms underlying stem cell aging and for development of some form of anti-aging intervention, thus contributing to prolongation of healthy life expectancy.

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

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Reviews, Commentaries, etc. 【 Display / hide

Presentations 【 Display / hide

  • オルガノイドモデルで解明する老化におけるエピゲノムの意義

    齋藤義正

    第110回日本病理学会総会, 2021.04, Symposium, Workshop, Panelist (nomination)

  • 難治性がんオルガノイドを用いた創薬研究

    齋藤義正

    第20回日本再生医療学会総会, 2021.03, Symposium, Workshop, Panelist (nomination)

  • エピジェネティクスと老化

    齋藤義正

    日本抗加齢医学会講習会, 2020.10, Public discourse, seminar, tutorial, course, lecture and others

  • マイクロ流体デバイスでの共培養モデルにおいて、肝星細胞は胆管癌オルガノイドの浸潤を抑制する

    須田雄大、齋藤義正

    第79回日本癌学会学術総会, 2020.10, Oral Presentation(general)

  • ヒト肝内胆管癌(IHCC)に対するスタチンの抑制効果

    富永皓斗、櫻井美帆、齋藤義正

    第79回日本癌学会学術総会, 2020.10, Oral Presentation(general)

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

  • 抗真菌薬を基盤とした胆道・膵臓がんに対する新規治療薬の創製

    2020.04
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 齋藤 義正, Grant-in-Aid for Scientific Research (B), Principal Investigator

  • NAD+およびエピゲノムの制御による老化メカニズムの解明と新たな抗加齢介入の開発

    2019.06
    -
    2021.03

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

  • オルガノイド培養による胆道・膵臓腫瘍細胞バンクの構築と個別化治療への応用

    2017.04
    -
    2020.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 齋藤 義正, Grant-in-Aid for Scientific Research (B), Principal Investigator

  • Investigation of the molecular mechanism underlying aging based on epigenome alterations in intestinal epithelial stem cells

    2016.04
    -
    2018.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 齋藤 義正, Grant-in-Aid for Challenging Exploratory Research, Principal Investigator

  • Diagnostic and therapeutic strategies targeting microRNAs and epigenome alterations in biliary tract and pancreatic cancer stem cells

    2014.04
    -
    2017.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 齋藤 義正, Grant-in-Aid for Scientific Research (B), Principal Investigator

     View Summary

    Cancer stem cells are resistant to conventional chemotherapies and responsible for cancer initiation, invasive growth, and metastasis formation. The aim of this study is to develop a novel therapeutic strategy targeting biliary tract and pancreatic cancer stem cells. The newly developed 3D culture system called “organoid culture” allows long-term expansion of LGR5 positive stem cells into budding cyst-like structures (organoids) with properties resembling those of the original tissues. To reach our goal, we established organoids derived from biliary tract cancers and pancreatic cancers. We analyzed gene mutation and gene expression and performed drug screening test using these cancer organoids. Here we demonstrated that low molecular compounds and tumor suppressor microRNAs including miR-34a are safe and effective therapeutic drug candidates against biliary tract and pancreatic cancers.

Intellectual Property Rights, etc. 【 Display / hide

  • がん幹細胞集団の調製方法、異種移植片の調製方法、スクリーニング方法、miR-34aの発現量を低下させる方法及びがん幹細胞増殖抑制剤

    Application No.: 特願2015-142164  2015.07 

    Patent, Joint, National application

Awards 【 Display / hide

  • Asian Pacific Digestive Week 2018, Emerging Leader Lectureship

    2018.11

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

  • 第18回日本抗加齢医学会総会 最優秀演題賞

    齋藤義正, 2018.05, 腸管上皮オルガノイドを用いたステムセルエイジングの検討

    Type of Award: Awards of National Conference, Council and Symposium.  Country: 日本

  • 日本抗加齢医学会優秀演題賞 

    木村真規、井手晴香、白井栄里奈、内田諒英、齋藤義正、齋藤英胤. , 2016.06, 第16回 日本抗加齢医学会総会, 高脂肪食摂取時の脂肪組織における老化マーカー遺伝子の発現変化とDNAメチル化阻害薬の効果. 

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

     View Description

    プログラム・抄録集: 170, 2016/6/10/12.

  • 日本抗加齢医学会優秀演題賞 

    内田諒英、齋藤義正、中岡哉彰、村松俊英、木村真規、齋藤英胤. , 2016.06, 第16回 日本抗加齢医学会総会 プログラム・抄録集: 174, 2016/6/10/12., オルガノイド培養法により樹立した腸管上上皮幹細胞における stem cell aging の検討. 

     View Description

    プログラム・抄録集: 174, 2016/6/10/12.

  • 慶應義塾大学薬学部学部長賞

    2015

    Type of Award: Keio commendation etc.

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Courses Taught 【 Display / hide

  • STUDY OF MAJOR FIELD: (PHARMACOTHERAPEUTICS)

    2021

  • SEMINAR:(PHARMACOTHERAPEUTICS)

    2021

  • RESEARCH FOR BACHELOR'S THESIS 1

    2021

  • REGULATORY SCIENCE ADVANCED COURSE

    2021

  • PRE-CLINICAL TRAINING FOR HOSPITAL & COMMUNITY PHARMACY

    2021

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