Details of the Researcher

PHOTO

Ritsuko Shimizu
Section
Graduate School of Medicine
Job title
Professor
Degree

  • 博士（医学）（自治医科大学）

Research History 7

  • 2009/04 - Present
    東北大学　教授

  • 1999/04 - 2009/03
    筑波大学　講師

  • 2002/09 - 2003/09
    ミシガン大学

  • 1998/10 - 1999/03
    筑波大学　リサーチアソシエイト

  • 1992/06 - 1998/09
    自治医科大学　助手

  • 1990/05 - 1992/05
    芳賀赤十字病院　医員

  • 1988/04 - 1990/04
    慶應義塾大学付属病院　研修医

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Education 1

  • Keio University　Faculty of Medicine

    - 1988/03/31

Research Areas 1

  • Life sciences / Hematology and oncology /

Awards 1

  1. Young Investigator's Award of the Japanese Society of Hematology

    2001/04/20　日本血液学会

Papers 124

  1. Co-stimulation with high-fat diet and acidic bile salts may promote Warburg effect in gastric carcinogenesis around the squamo-columnar junction in Gan mice

    Koichiro Sudo, Kaname Uno, Toru Tamahara, Naoki Asano, Keisuke Kusano, Mizuki Tanabe, Kouya Ogasawara, Takeshi Kanno, Tomoyuki Koike, Ritsuko Shimizu, Atsushi Masamune

    American Journal of Physiology-Gastrointestinal and Liver Physiology　2025/04/17

    Publisher: American Physiological Society

    DOI： 10.1152/ajpgi.00305.2024 　

    ISSN： 0193-1857

    eISSN： 1522-1547

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    Epidemiological studies demonstrated relationships between gastric cardia adenocarcinoma (GCA) and metabolic syndrome (MetS). We aimed to clarify mechanism underlying their relationship. To investigate whether systemic inflammation against high-fat diet (HFD)-related dysbiosis promotes Warburg effect in tumors at the squamo-columnar junction (SCJ), we applied K19-Wnt1/C2mE (Gan) mice, fed either HFD or control diet ± acidic bile salts (ABS) with/without clodronate liposomes (CLs), and in vitro studies using MKN7 cells with/without THP1-derived macrophages. Then, we assessed involvement of oxidative stress (OS) in Warburg effect by comparing between nuclear factor-erythroid 2-related factor 2 (Nrf2) knockout-Gan mice and Gan mice. Tumors with macrophage infiltration in HFD+ABS group were larger than in Control group. Gene Set Enrichment Analysis revealed enhancement of the OS signaling in tumor of HFD+ABS group. HFD+ABS group mice demonstrated induction of OS, Nqo1, TNFα, and Warburg effect in tumors and mucosal barrier dysfunction of dysbiotic gut. All of them were abolished with diminishing macrophage infiltration by additional CLs treatment. Stimulation with TNFα, but not ABS nor lipopolysaccharide, on MKN7 cells activated Warburg effect. In MKN7 cells co-cultured with the macrophages whose TNFa expression was induced by the lipopolysaccharide pretreatment, Warburg effect was enhanced in the TNFα concentration-dependent manners. In Nrf2 knockout-Gan mice, tumors shrank with reducing OS, TNFα, and Warburg effect, along with decreasing macrophage infiltration. Accordingly, MetS may develop GCA through the Nrf2-related Warburg effect under the TNFα stimulation from the macrophages activated by both local ABS exposure and systemic lipopolysaccharide exposure from leaky gut with HFD-related dysbiosis.

  2. Urgent Notification Intervention of Home Blood Pressure in Cohort Studies of the Tohoku Medical Megabank Project.

    Eiichi N Kodama, Makiko Taira, Hideyasu Kiyomoto, Tomohiro Nakamura, Satoshi Nagaie, Shinichi Kuriyama, Atsushi Hozawa, Junichi Sugawara, Fuji Nagami, Akira Uruno, Jun Nakaya, Hirohito Metoki, Masaki Sakaida, Masahiro Kikuya, Yoichi Suzuki, Kiyoshi Ito, Yohei Hamanaka, Kichiya Suzuki, Shigeo Kure, Nobuo Yaegashi, Nobuo Fuse, Ritsuko Shimizu, Masayuki Yamamoto

    JMA journal　7　(3)　342-352　2024/07/16

    DOI： 10.31662/jmaj.2023-0215 　

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    INTRODUCTION: The Tohoku Medical Megabank (TMM) was established for creative reconstruction from the Great East Japan Earthquake and tsunami in 2011. Two prospective genome cohort studies in Miyagi prefecture have successfully recruited approximately 127,000 participants. The health status of these individuals was evaluated at the initial recruitment, and follow-up health checkups have been conducted every 5 years. During these health checkups, unexpected critical values were encountered, which prompted us to develop an urgent notification system. METHODS: We analyzed the frequency of critical values observed in home blood pressure (HBP) test in an urgent notification office (UNO). We returned the critical values by urgent notification before the notifications of regular results. In addition, the impact of the TMM urgent notification on the participants was evaluated. RESULTS: We issued urgent notifications of the critical values of extremely high HBP. Of the 21,061 participants who underwent HBP measurements, 256 (1.2%) met the criteria for urgent notification. It was found that abnormalities in blood sugar levels, renal function, and lipid values were frequently concurrent with the abnormal HBP readings. Annual questionnaires administered after the urgent notification, approximately 60% of those went to hospitals or clinics. CONCLUSIONS: The urgent notification system for hypertensive emergency with HBP in the TMM was well accepted by the participants and encouraged them to seek medical care. The system has been useful in addressing the prolonged healthcare problems and in promoting health care in large-scale disaster damaged areas.

  3. Sequential Sampling of the Gastrointestinal Tract to Characterize the Entire Digestive Microbiome in Japanese Subjects. International-journal

    Kota Ishizawa, Toru Tamahara, Suguo Suzuki, Yutaka Hatayama, Bin Li, Michiaki Abe, Yuichi Aoki, Ryutaro Arita, Natsumi Saito, Minoru Ohsawa, Soichiro Kaneko, Rie Ono, Shin Takayama, Muneaki Shimada, Kazuki Kumada, Tomoyuki Koike, Atsushi Masamune, Ko Onodera, Tadashi Ishii, Ritsuko Shimizu, Takeshi Kanno

    Microorganisms　12　(7)　2024/06/28

    DOI： 10.3390/microorganisms12071324 　

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    The gastrointestinal (GI) tract harbors trillions of microorganisms known to influence human health and disease, and next-generation sequencing (NGS) now enables the in-depth analysis of their diversity and functions. Although a significant amount of research has been conducted on the GI microbiome, comprehensive metagenomic datasets covering the entire tract are scarce due to cost and technical challenges. Despite the widespread use of fecal samples, integrated datasets encompassing the entire digestive process, beginning at the mouth and ending with feces, are lacking. With this study, we aimed to fill this gap by analyzing the complete metagenome of the GI tract, providing insights into the dynamics of the microbiota and potential therapeutic avenues. In this study, we delved into the complex world of the GI microbiota, which we examined in five healthy Japanese subjects. While samples from the whole GI flora and fecal samples provided sufficient bacteria, samples obtained from the stomach and duodenum posed a challenge. Using a principal coordinate analysis (PCoA), clear clustering patterns were identified; these revealed significant diversity in the duodenum. Although this study was limited by its small sample size, the flora in the overall GI tract showed unwavering consistency, while the duodenum exhibited unprecedented phylogenetic diversity. A visual heat map illustrates the discrepancy in abundance, with Fusobacteria and Bacilli dominating the upper GI tract and Clostridia and Bacteroidia dominating the fecal samples. Negativicutes and Actinobacteria were found throughout the digestive tract. This study demonstrates that it is possible to continuously collect microbiome samples throughout the human digestive tract. These findings not only shed light on the complexity of GI microbiota but also provide a basis for future research.

  4. Activation of NOTCH signaling impedes cell proliferation and survival in acute megakaryoblastic leukemia. International-journal

    Kelly Ooi Kee Ong, Michelle Meng Huang Mok, Akiko Niibori-Nambu, Linsen Du, Masatoshi Yanagida, Chelsia Qiuxia Wang, Avinash Govind Bahirvani, Desmond Wai Loon Chin, Cai Ping Koh, King Pan Ng, Namiko Yamashita, Bindya Jacob, Tomomasa Yokomizo, Hitoshi Takizawa, Takayoshi Matsumura, Toshio Suda, Jie-Ying Amelia Lau, Tuan Zea Tan, Seiichi Mori, Henry Yang, Masayuki Iwasaki, Takashi Minami, Norio Asou, Qiao-Yang Sun, Ling-Wen Ding, H Phillip Koeffler, Daniel G Tenen, Ritsuko Shimizu, Masayuki Yamamoto, Yoshiaki Ito, Shirley Kow Yin Kham, Allen Eng-Juh Yeoh, Wee Joo Chng, Motomi Osato

    Experimental hematology　137　104255-104255　2024/06/13

    DOI： 10.1016/j.exphem.2024.104255 　

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    The genetic lesions that drive acute megakaryoblastic leukemia (AMKL) have not been fully elucidated. To search for genetic alterations in AMKL, we performed targeted deep sequencing in 34 AMKL patient samples and 8 AMKL cell lines and detected frequent genetic mutations in the NOTCH pathway in addition to previously reported alterations in GATA-1 and the JAK-STAT pathway. Pharmacological and genetic NOTCH activation, but not inhibition, significantly suppressed AMKL cell proliferation in both in vitro and in vivo assays employing a patient-derived xenograft model. These results suggest that NOTCH inactivation underlies AMKL leukemogenesis. and NOTCH activation holds the potential for therapeutic application in AMKL.

  5. The Significance of Bile in the Biliopancreatic Limb on Metabolic Improvement After Duodenal-Jejunal Bypass. International-journal

    Tomomi Kawana, Hirofumi Imoto, Naoki Tanaka, Takahiro Tsuchiya, Akihiro Yamamura, Fumito Saijo, Masamitsu Maekawa, Toru Tamahara, Ritsuko Shimizu, Kei Nakagawa, Shinobu Ohnuma, Takashi Kamei, Michiaki Unno

    Obesity surgery　34　(5)　1665-1673　2024/05

    DOI： 10.1007/s11695-024-07176-7 　

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    INTRODUCTION: Duodenal-jejunal bypass (DJB) is an experimental procedure in metabolic surgery that does not have a restrictive component. Changes in bile acid (BA) dynamics and intestinal microbiota are possibly related to metabolic improvement after DJB. Our previous studies involving obese diabetic rats showed the crucial role of the biliopancreatic limb (BPL) in metabolic improvement after DJB caused by BA reabsorption. We established a new DJB procedure to prevent bile from flowing into the BPL and aimed to elucidate the importance of bile in the BPL after DJB. METHODS: Otsuka Long-Evans Tokushima Fatty rats with diabetes were divided into three groups: two DJB groups and a sham group (n = 11). Duodenal-jejunal anastomosis was performed proximal to the papilla of Vater in the DJB group (n = 11). However, the DJB-D group (n = 11) underwent a new procedure with duodenal-jejunal anastomosis distal to the papilla of Vater for preventing bile flow into the BPL. RESULTS: Glucose metabolism improved and weight gain was suppressed in the DJB group, but not in the DJB-D and sham groups. Serum BA level and conjugated BA concentration were elevated in the DJB group. The gut microbiota was altered only in the DJB group; the abundance of Firmicutes and Bacteroidetes decreased and that of Actinobacteria increased. However, the DJB-D group exhibited no apparent change in the gut microbiota, similar to the sham group. CONCLUSION: BAs are essential in the BPL for metabolic improvement after DJB; they can improve the gut microbiota in these processes.

  6. Intracanal microbiome profiles of two apical periodontitis cases in one patient: A comparison with saliva and plaque profiles. International-journal Peer-reviewed

    Keiko Yamaki, Toru Tamahara, Jumpei Washio, Takuichi Sato, Ritsuko Shimizu, Satoru Yamada

    Clinical and experimental dental research　10　(2)　e862　2024/04

    DOI： 10.1002/cre2.862 　

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    OBJECTIVES: To determine the characteristics of the endodontic microbiome. MATERIAL AND METHODS: Saliva, plaque, and infected root canal wall dentin of two teeth suffering from apical periodontitis were harvested from a 58-year-old man. Bacterial DNA was extracted from each sample, and 16S rRNA gene analysis targeting the V3-V4 region was conducted on the Illumina MiSeq platform using QIIME2. The functional potential of the microbiomes was inferred using PICRUSt2. RESULTS: The four microbiomes were different in structure and membership, yet the nine most abundant metabolic pathways were common among them. The two endodontic microbiomes were more anaerobic, rich in Firmicutes, and scarce in Actinobacteriota and Proteobacteria, compared with saliva and plaque microbiomes. Their profiles were dissimilar despite their clinical and radiographic similarities. CONCLUSIONS: The endodontic microbiomes were anaerobic, rich in Firmicutes, scarce in Actinobacteriota and Proteobacteria, and considerably varied within an individual.

  7. Strain-dependent modifiers exacerbate familial leukemia caused by GATA1-deficiency. International-journal

    Ikuo Hirano, Kanako Abe, James Douglas Engel, Masayuki Yamamoto, Ritsuko Shimizu

    Experimental hematology & oncology　13　(1)　23-23　2024/02/26

    DOI： 10.1186/s40164-024-00491-w 　

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    GATA1 plays a critical role in differentiation, proliferation, and apoptosis during erythropoiesis. We developed a Gata1 knock-down allele (Gata1.05) that results in GATA1 expression at 5% of endogenous level. In female mice heterozygous for both the Gata1.05 and wild-type alleles, we observed a predisposition to erythroblastic leukemia three to six months after birth. Since no male Gata1.05 progeny survive gestation, we originally maintained heterozygous females in a mixed genetic background of C57BL/6J and DBA/2 strains. Around 30% of these mice reproducibly develop leukemia, but the other subset did not develop leukemia, even though they harbor a high number of preleukemic erythroblasts. These observations prompted us to hypothesize that there may be potential influence of genetic determinants on the progression of Gata1.05-driven hematopoietic precursors to full-blown leukemia. In an initial examination of Gata1.05/X mice backcrossed into C3H/He, BALB/c, DBA/2, C57BL/6J and 129X1/SvJ strains, we discerned that the backgrounds of C57BL/6J and 129X1/SvJ significantly expedited leukemia onset in Gata1.05/X mice. Conversely, backgrounds of C3H/He, BALB/c and DBA/2 did not substantially modify the effect of the Gata1 mutation. This indicates the existence of genetic modifiers that accentuate Gata1.05 leukemogenesis. Subsequent cohort studies evaluated Gata1.05/X mice within mix backgrounds of BALB/c:129X1/SvJ and BALB/c:C57BL/6J. In these settings, Gata1.05-driven leukemia manifested in autosomal dominant patterns within the 129X1/SvJ background and in autosomal recessive patterns within C57BL/6J background. To the best of our knowledge, this study provides the inaugural evidence of genetic modifiers that can reshape the outcome based on leukemia-associated gene signatures.

  8. The abundance of the short GATA1 isoform affects megakaryocyte differentiation and leukemic predisposition in mice. International-journal

    Daishi Ishihara, Atsushi Hasegawa, Ikuo Hirano, James Douglas Engel, Masayuki Yamamoto, Ritsuko Shimizu

    Experimental hematology & oncology　13　(1)　24-24　2024/02/26

    DOI： 10.1186/s40164-024-00492-9 　

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    Transcription factor GATA1 controls the delicate balance between proliferation, differentiation and apoptosis in both the erythroid and megakaryocytic lineages. In addition to full-length GATA1, there is an GATA1 isoform, GATA1s, that lacks the amino-terminal transactivation domain. Somatic GATA1 mutations that lead to the exclusive production of GATA1s appear to be necessary and sufficient for the development of a preleukemic condition called transient myeloproliferative disorder (TMD) in Down syndrome newborns. Subsequent clonal evolution among latent TMD blasts leads to the development of acute megakaryoblastic leukemia (AMKL). We originally established transgenic mice that express only GATA1s, which exhibit hyperproliferation of immature megakaryocytes, thus mimicking human TMD; however, these mice never developed AMKL. Here, we report that transgenic mice expressing moderate levels of GATA1s, i.e., roughly comparable levels to endogenous GATA1, were prone to develop AMKL in young adults. However, when GATA1s is expressed at levels significantly exceeding that of endogenous GATA1, the development of leukemia was restrained in a dose dependent manner. If the transgenic increase of GATA1s in progenitors remains small, GATA1s supports the terminal maturation of megakaryocyte progenitors insufficiently, and consequently the progenitors persisted, leading to an increased probability for acquisition of additional genetic modifications. In contrast, more abundant GATA1s expression compensates for this maturation block, enabling megakaryocytic progenitors to fully differentiate. This study provides evidence for the clinical observation that the abundance of GATA1s correlates well with the progression to AMKL in Down syndrome.

  9. Progress report of the Tohoku Medical Megabank Community-Based Cohort Study: Study profile of the repeated center-based survey during second period in Miyagi Prefecture.

    Atsushi Hozawa, Kumi Nakaya, Naoki Nakaya, Tomohiro Nakamura, Mana Kogure, Rieko Hatanaka, Ippei Chiba, Ikumi Kanno, Junichi Sugawara, Eiichi Kodama, Yohei Hamanaka, Tomoko Kobayashi, Akira Uruno, Naho Tsuchiya, Takumi Hirata, Akira Narita, Akito Tsuboi, Toru Tamahara, Akihito Otsuki, Maki Goto, Makiko Taira, Ritsuko Shimizu, Kichiya Suzuki, Taku Obara, Masahiro Kikuya, Hirohito Metoki, Mami Ishikuro, Inaho Danjoh, Soichi Ogishima, Satoshi Nagaie, Naoko Minegishi, Masahiro Hiratsuka, Kazuki Kumada, Ichiko Nishijima, Takahiro Nobukuni, Yumi Yamaguchi-Kabata, Fuji Nagami, Shigeo Kure, Nobuo Fuse, Kengo Kinoshita, Yoko Izumi, Shinichi Kuriyama, Masayuki Yamamoto

    Journal of epidemiology　2024/02/24

    DOI： 10.2188/jea.JE20230241 　

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    BACKGROUND: The purpose of this study was to report the basic profile of the Miyagi Prefecture part of a repeated center-based survey during the second period (2nd period survey) of the Tohoku Medical Megabank Community-Based Cohort Study (TMM CommCohort Study), as well as the participants' characteristics based on their participation type in the baseline survey. METHODS: The 2nd period survey, conducted from June 2017 to March 2021, included participants of the TMM CommCohort Study (May 2013 to March 2016). In addition to the questionnaire, blood, urine, and physiological function tests were performed during the 2nd period survey. There were three main ways of participation in the baseline survey: Type 1, Type 1 additional, or Type 2 survey. The 2nd period survey was conducted in the same manner as the Type 2 survey, which was based on the community support center (CSC). RESULTS: In Miyagi Prefecture, 29,383 (57.7%) of 50,967 participants participated in the 2nd period survey. The participation rate among individuals who had visited the CSC was approximately 80%. Although some factors differed depending on the participation type in the baseline survey, the 2nd period survey respondents in the Type 1 and Type 2 survey groups at baseline had similar traits. CONCLUSIONS: The 2nd period survey of the TMM CommCohort Study provided detailed follow-up information. Following up on the health conditions of the participants will clarify the long-term effects of disasters and contribute to personalized prevention.

  10. jMorp: Japanese Multi-Omics Reference Panel update report 2023. International-journal Peer-reviewed

    Shu Tadaka, Junko Kawashima, Eiji Hishinuma, Sakae Saito, Yasunobu Okamura, Akihito Otsuki, Kaname Kojima, Shohei Komaki, Yuichi Aoki, Takanari Kanno, Daisuke Saigusa, Jin Inoue, Matsuyuki Shirota, Jun Takayama, Fumiki Katsuoka, Atsushi Shimizu, Gen Tamiya, Ritsuko Shimizu, Masahiro Hiratsuka, Ikuko N Motoike, Seizo Koshiba, Makoto Sasaki, Masayuki Yamamoto, Kengo Kinoshita

    Nucleic acids research　2023/11/01

    DOI： 10.1093/nar/gkad978 　

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    Modern medicine is increasingly focused on personalized medicine, and multi-omics data is crucial in understanding biological phenomena and disease mechanisms. Each ethnic group has its unique genetic background with specific genomic variations influencing disease risk and drug response. Therefore, multi-omics data from specific ethnic populations are essential for the effective implementation of personalized medicine. Various prospective cohort studies, such as the UK Biobank, All of Us and Lifelines, have been conducted worldwide. The Tohoku Medical Megabank project was initiated after the Great East Japan Earthquake in 2011. It collects biological specimens and conducts genome and omics analyses to build a basis for personalized medicine. Summary statistical data from these analyses are available in the jMorp web database (https://jmorp.megabank.tohoku.ac.jp), which provides a multidimensional approach to the diversity of the Japanese population. jMorp was launched in 2015 as a public database for plasma metabolome and proteome analyses and has been continuously updated. The current update will significantly expand the scale of the data (metabolome, genome, transcriptome, and metagenome). In addition, the user interface and backend server implementations were rewritten to improve the connectivity between the items stored in jMorp. This paper provides an overview of the new version of the jMorp.

  11. Nrf2 alleviates spaceflight-induced immunosuppression and thrombotic microangiopathy in mice Peer-reviewed

    Shimizu R, Hirano I, Hasegawa A, Suzuki M, Otsuki A, Taguchi K, Katsuoka F, Uruno A, Suzuki N, Yumoto A, Okada R, Shrakawa M, Shiba D, Takahashi S, Suzuki T, Yamamoto M

    Commun Biol　6　2023/08

    DOI： 10.1038/s42003-022-03316-w 　

  12. Tohoku Medical Megabank Brain Magnetic Resonance Imaging Study: Rationale, Design, and Background Peer-reviewed

    Makiko Taira, Shunji Mugikura, Naoko Mori, Atsushi Hozawa, Tomo Saito, Tomohiro Nakamura, Hideyasu Kiyomoto, Tadao Kobayashi, Soichi Ogishima, Fuji Nagami, Akira Uruno, Ritsuko Shimizu, Tomoko Kobayashi, Jun Yasuda, Shigeo Kure, Miyuki Sakurai, Ikuko N. Motoike, Kazuki Kumada, Naoki Nakaya, Taku Obara, Kentaro Oba, Atsushi Sekiguchi, Benjamin Thyreau, Tatsushi Mutoh, Yuji Takano, Mitsunari Abe, Norihide Maikusa, Yasuko Tatewaki, Yasuyuki Taki, Nobuo Yaegashi, Hiroaki Tomita, Kengo Kinoshita, Shinichi Kuriyama, Nobuo Fuse, Masayuki Yamamoto

    JMA Journal　6　(3)　246-264　2023/07

    Publisher: Japan Medical Association

    DOI： 10.31662/jmaj.2022-0220 　

    ISSN： 2433-328X

    eISSN： 2433-3298

  13. Recent progress in analyses of GATA1 in hematopoietic disorders: a mini-review Peer-reviewed

    Ritsuko Shimizu, Masayuki Yamamoto

    Frontiers in Hematology　2　2023/05/03

    Publisher: Frontiers Media SA

    DOI： 10.3389/frhem.2023.1181216 　

    eISSN： 2813-3935

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    GATA1 is an essential master regulator of erythropoiesis and megakaryopoiesis. Accumulating lines of evidence have shown that dynamic changes in GATA1 gene expression levels during erythropoiesis are crucial for proper erythroid differentiation. Since GATA1 is an X-chromosome gene, GATA1 knockout leads to embryonic lethal dyserythropoiesis in male mice, while heterozygous female mice can survive. In the past decade, it has become clear that germline GATA1 gene mutations leading to structural changes in the GATA1 protein are involved in congenital dyserythropoiesis in males. In contrast, decreased GATA1 expression levels, which cause embryonic lethal dyserythropoiesis in male mice, increase the risk of erythroleukemia development in female mice, while female GATA1-knockout mice do not show substantial phenotypic alterations in erythroid or megakaryocyte lineages. In this review, we summarize the recent progress in elucidating the roles of GATA1 in normal and pathogenetic erythropoiesis and discuss the possible mechanisms of pathogenesis of dyserythropoiesis and erythroleukemia.

  14. Design and Progress of Child Health Assessments at Community Support Centers in the Birth and Three-Generation Cohort Study of the Tohoku Medical Megabank Project. Peer-reviewed

    Tomoko Kobayashi, Mika Kobayashi, Naoko Minegishi, Masahiro Kikuya, Taku Obara, Mami Ishikuro, Chizuru Yamanaka, Tomomi Onuma, Keiko Murakami, Fumihiko Ueno, Aoi Noda, Akira Uruno, Junichi Sugawara, Kichiya Suzuki, Eiichi N Kodama, Yohei Hamanaka, Naho Tsuchiya, Mana Kogure, Naoki Nakaya, Makiko Taira, Mika Sakurai-Yageta, Toru Tamahara, Junko Kawashima, Maki Goto, Akihito Otsuki, Ritsuko Shimizu, Soichi Ogishima, Hiroaki Hashizume, Fuji Nagami, Tomohiro Nakamura, Atsushi Hozawa, Tadao Kobayashi, Nobuo Fuse, Shinichi Kuriyama, Shigeo Kure, Masayuki Yamamoto

    The Tohoku journal of experimental medicine　259　(2)　93-105　2023/01/20

    DOI： 10.1620/tjem.2022.J103 　

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    The Tohoku Medical Megabank Project (TMM) has been conducting a birth and three-generation cohort study (the BirThree Cohort Study). We recruited 73,529 pregnant women and their family members for this cohort study, which included 23,143 newborns and 9,459 of their siblings. We designed and are in the process of conducting three-step health assessments for each newborn at approximately ages of 5, 10 and 16. These health assessments are administered at seven community support centers. Trained genome medical research coordinators conduct physical examinations of and collect biological specimens from each participant. The Sendai Children's Health Square has been established as the headquarters for these child health assessments and is utilized to accumulate knowledge that can facilitate the proper practice of child health assessments. We designed all the relevant health assessments facilities to allow parents and their children to participate in the health assessments concomitantly. Our centers serve as places where child participants and their parents can feel at ease as a result of the implementation of safety measures and child hospitality measures. The TMM BirThree Cohort Study is in the process of conducting strategically detailed health assessments and genome analysis, which can facilitate studies concerning the gene-environment interactions relevant to noncommunicable diseases. Through these operations, our study allows for a significant depth of data to be collected in terms of the number of biospecimens under study and the comprehensiveness of both basic and clinical data alongside relevant family information.

  15. 口腔内細菌叢の破綻と全身疾患のかかわりを捉える 大規模ゲノムコホート調査でマイクロバイオームを標的とした疾患研究の基盤を築く

    齋藤さかえ, 齋藤さかえ, 清水律子

    Microbiome Science　2　(2)　2023

    ISSN： 2758-2094

  16. Heterozygous variants in GATA2 contribute to DCML deficiency in mice by disrupting tandem protein binding Peer-reviewed

    Atsushi Hasegawa, Yuki Hayasaka, Masanobu Morita, Yuta Takenaka, Yuna Hosaka, Ikuo Hirano, Masayuki Yamamoto, Ritsuko Shimizu

    Communications Biology　5　(1)　2022/12

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s42003-022-03316-w 　

    eISSN： 2399-3642

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    Abstract Accumulating lines of clinical evidence support the emerging hypothesis that loss-of-function mutations of GATA2 cause inherited hematopoietic diseases, including Emberger syndrome; dendritic cell, monocyte B and NK lymphoid (DCML) deficiency; and MonoMAC syndrome. Here, we show that mice heterozygous for an arginine-to-tryptophan substitution mutation in GATA2 (G2R398W/+), which was found in a patient with DCML deficiency, substantially phenocopy human DCML deficiency. Mice heterozygous for the GATA2-null mutation (G2-/+) do not show such phenotypes. The G2R398W protein possesses a decreased DNA-binding affinity but obstructs the function of coexpressed wild-type GATA2 through specific cis-regulatory regions, which contain two GATA motifs in direct-repeat arrangements. In contrast, G2R398W is innocuous in mice containing single GATA motifs. We conclude that the dominant-negative effect of mutant GATA2 on wild-type GATA2 through specific enhancer/silencer of GATA2 target genes perturbs the GATA2 transcriptional network, leading to the development of the DCML-like phenotype. The present mouse model provides an avenue for the understanding of molecular mechanisms underlying the pathogenesis of GATA2-related hematopoietic diseases.

  17. Characterization and Demonstration of Mock Communities as Control Reagents for Accurate Human Microbiome Community Measurements. International-journal Peer-reviewed

    Dieter M Tourlousse, Koji Narita, Takamasa Miura, Akiko Ohashi, Masami Matsuda, Yoshifumi Ohyama, Mamiko Shimamura, Masataka Furukawa, Ken Kasahara, Keishi Kameyama, Sakae Saito, Maki Goto, Ritsuko Shimizu, Riko Mishima, Jiro Nakayama, Koji Hosomi, Jun Kunisawa, Jun Terauchi, Yuji Sekiguchi, Hiroko Kawasaki

    Microbiology spectrum　10　(2)　e0191521　2022/04/27

    DOI： 10.1128/spectrum.01915-21 　

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    Standardization and quality assurance of microbiome community analysis by high-throughput DNA sequencing require widely accessible and well-characterized reference materials. Here, we report on newly developed DNA and whole-cell mock communities to serve as control reagents for human gut microbiota measurements by shotgun metagenomics and 16S rRNA gene amplicon sequencing. The mock communities were formulated as near-even blends of up to 20 bacterial species prevalent in the human gut, span a wide range of genomic guanine-cytosine (GC) contents, and include multiple strains with Gram-positive type cell walls. Through a collaborative study, we carefully characterized the mock communities by shotgun metagenomics, using previously developed standardized protocols for DNA extraction and sequencing library construction. Further, we validated fitness of the mock communities for revealing technically meaningful differences among protocols for DNA extraction and metagenome/16S rRNA gene amplicon library construction. Finally, we used the mock communities to reveal varying performance of metagenome-based taxonomic profilers and the impact of trimming and filtering of sequencing reads on observed species profiles. The latter showed that aggressive preprocessing of reads may result in substantial GC-dependent bias and should thus be carefully evaluated to minimize unintended effects on species abundances. Taken together, the mock communities are expected to support a myriad of applications that rely on well-characterized control reagents, ranging from evaluation and optimization of methods to assessment of reproducibility in interlaboratory studies and routine quality control. IMPORTANCE Application of high-throughput DNA sequencing has greatly accelerated human microbiome research and its translation into new therapeutic and diagnostic capabilities. Microbiome community analyses results can, however, vary considerably across studies or laboratories, and establishment of measurement standards to improve accuracy and reproducibility has become a priority. The here-developed mock communities, which are available from the NITE Biological Resource Center (NBRC) at the National Institute of Technology and Evaluation (NITE, Japan), provide well-characterized control reagents that allow users to judge the accuracy of their measurement results. Widespread and consistent adoption of the mock communities will improve reproducibility and comparability of microbiome community analyses, thereby supporting and accelerating human microbiome research and development.

  18. Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan International-journal Peer-reviewed

    Nobuo Fuse, Miyuki Sakurai, Ikuko N. Motoike, Kaname Kojima, Takako Takai-Igarashi, Naoki Nakaya, Naho Tsuchiya, Tomohiro Nakamura, Mami Ishikuro, Taku Obara, Akiko Miyazawa, Kei Homma, Keisuke Ido, Makiko Taira, Tomoko Kobayashi, Ritsuko Shimizu, Akira Uruno, Eiichi N. Kodama, Kichiya Suzuki, Yohei Hamanaka, Hiroaki Tomita, Junichi Sugawara, Yoichi Suzuki, Fuji Nagami, Soichi Ogishima, Fumiki Katsuoka, Naoko Minegishi, Atsushi Hozawa, Shinichi Kuriyama, Nobuo Yaegashi, Shigeo Kure, Kengo Kinoshita, Masayuki Yamamoto

    Ophthalmology Science　2　(1)　100113-100113　2022/03

    Publisher: Elsevier BV

    DOI： 10.1016/j.xops.2022.100113 　

    ISSN： 2666-9145

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    PURPOSE: To elucidate the differences in ocular biometric parameters by generation and gender and to identify axial length (AL)-associated genetic variants in Japanese individuals, we analyzed Tohoku Medical Megabank Organization (ToMMo) Eye Study data. DESIGN: We designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs). PARTICIPANTS: In total, 33 483 participants aged > 18 years who were recruited into the community-based cohort (CommCohort) and the birth and three-generation cohort (BirThree Cohort) of the ToMMo Eye Study were examined. METHODS: Each participant was screened with an interview, ophthalmic examinations, and a microarray analysis. The GWASs were performed in 22 379 participants in the CommCohort (discovery stage) and 11 104 participants in the BirThree Cohort (replication stage). We evaluated the associations of single nucleotide polymorphisms (SNPs) with AL using a genome-wide significance threshold (5 × 10-8) in each stage of the study and in the subsequent meta-analysis. MAIN OUTCOME MEASURES: We identified the association of SNPs with AL and distributions of AL in right and left eyes and individuals of different sexes and ages. RESULTS: In the discovery stage, the mean AL of the right eye (23.99 mm) was significantly greater than that of the left eye (23.95 mm). This difference was reproducible across sexes and ages. The GWASs revealed 703 and 215 AL-associated SNPs with genome-wide significance in the discovery and validation stages, respectively, and many of the SNPs in the discovery stage were replicated in the validation stage. Validated SNPs and their associated loci were meta-analyzed for statistical significance (P < 5 × 10-8). This study identified 1478 SNPs spread over 31 loci. Of the 31 loci, 5 are known AL loci, 15 are known refractive-error loci, 4 are known corneal-curvature loci, and 7 loci are newly identified loci that are not known to be associated with AL. Of note, some of them shared functional relationships with previously identified loci. CONCLUSIONS: Our large-scale GWASs exploiting ToMMo Eye Study data identified 31 loci linked to variations in AL, 7 of which are newly reported in this article. The results revealed genetic heterogeneity and similarity in SNPs related to ethnic variations in AL.

  19. Loss of Atg2b and Gskip Impairs the Maintenance of the Hematopoietic Stem Cell Pool Size. International-journal Peer-reviewed

    Shun-Suke Sakai, Atsushi Hasegawa, Ryosuke Ishimura, Naoki Tamura, Shun Kageyama, Satoko Komatsu-Hirota, Manabu Abe, Yiwei Ling, Shujiro Okuda, Manabu Funayama, Mika Kikkawa, Yoshiki Miura, Kenji Sakimura, Ichiei Narita, Satoshi Waguri, Ritsuko Shimizu, Masaaki Komatsu

    Molecular and cellular biology　42　(1)　e0002421　2022/01/20

    DOI： 10.1128/MCB.00024-21 　

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    A germ line copy number duplication of chromosome 14q32, which contains ATG2B and GSKIP, was identified in families with myeloproliferative neoplasm (MPN). Here, we show that mice lacking both Atg2b and Gskip, but not either alone, exhibited decreased hematopoiesis, resulting in death in utero accompanied by anemia. In marked contrast to MPN patients with duplication of ATG2B and GSKIP, the number of hematopoietic stem cells (HSCs), in particular long-term HSCs, in double-knockout fetal livers was significantly decreased due to increased cell death. Although the remaining HSCs still had the ability to differentiate into hematopoietic progenitor cells, the differentiation efficiency was quite low. Remarkably, mice with knockout of Atg2b or Gskip alone did not show any hematopoietic abnormality. Mechanistically, while loss of both genes had no effect on autophagy, it increased the expression of genes encoding enzymes involved in oxidative phosphorylation. Taken together, our results indicate that Atg2b and Gskip play a synergistic effect in maintaining the pool size of HSCs.

  20. dbTMM: an integrated database of large-scale cohort, genome and clinical data for the Tohoku Medical Megabank Project. International-journal Peer-reviewed

    Soichi Ogishima, Satoshi Nagaie, Satoshi Mizuno, Ryosuke Ishiwata, Keita Iida, Kazuro Shimokawa, Takako Takai-Igarashi, Naoki Nakamura, Sachiko Nagase, Tomohiro Nakamura, Naho Tsuchiya, Naoki Nakaya, Keiko Murakami, Fumihiko Ueno, Tomomi Onuma, Mami Ishikuro, Taku Obara, Shunji Mugikura, Hiroaki Tomita, Akira Uruno, Tomoko Kobayashi, Akito Tsuboi, Shu Tadaka, Fumiki Katsuoka, Akira Narita, Mika Sakurai, Satoshi Makino, Gen Tamiya, Yuichi Aoki, Ritsuko Shimizu, Ikuko N Motoike, Seizo Koshiba, Naoko Minegishi, Kazuki Kumada, Takahiro Nobukuni, Kichiya Suzuki, Inaho Danjoh, Fuji Nagami, Kozo Tanno, Hideki Ohmomo, Koichi Asahi, Atsushi Shimizu, Atsushi Hozawa, Shinichi Kuriyama, Nobuo Fuse, Teiji Tominaga, Shigeo Kure, Nobuo Yaegashi, Kengo Kinoshita, Makoto Sasaki, Hiroshi Tanaka, Masayuki Yamamoto

    Human genome variation　8　(1)　44-44　2021/12/10

    DOI： 10.1038/s41439-021-00175-5 　

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    To reveal gene-environment interactions underlying common diseases and estimate the risk for common diseases, the Tohoku Medical Megabank (TMM) project has conducted prospective cohort studies and genomic and multiomics analyses. To establish an integrated biobank, we developed an integrated database called "dbTMM" that incorporates both the individual cohort/clinical data and the genome/multiomics data of 157,191 participants in the Tohoku Medical Megabank project. To our knowledge, dbTMM is the first database to store individual whole-genome data on a variant-by-variant basis as well as cohort/clinical data for over one hundred thousand participants in a prospective cohort study. dbTMM enables us to stratify our cohort by both genome-wide genetic factors and environmental factors, and it provides a research and development platform that enables prospective analysis of large-scale data from genome cohorts.

  21. Nrf2 plays a critical role in the metabolic response during and after spaceflight. International-journal Peer-reviewed

    Akira Uruno, Daisuke Saigusa, Takafumi Suzuki, Akane Yumoto, Tomohiro Nakamura, Naomi Matsukawa, Takahiro Yamazaki, Ristumi Saito, Keiko Taguchi, Mikiko Suzuki, Norio Suzuki, Akihito Otsuki, Fumiki Katsuoka, Eiji Hishinuma, Risa Okada, Seizo Koshiba, Yoshihisa Tomioka, Ritsuko Shimizu, Masaki Shirakawa, Thomas W Kensler, Dai Shiba, Masayuki Yamamoto

    Communications biology　4　(1)　1381-1381　2021/12/09

    DOI： 10.1038/s42003-021-02904-6 　

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    Space travel induces stresses that contribute to health problems, as well as inducing the expression of Nrf2 (NF-E2-related factor-2) target genes that mediate adaptive responses to oxidative and other stress responses. The volume of epididymal white adipose tissue (eWAT) in mice increases during spaceflight, a change that is attenuated by Nrf2 knockout. We conducted metabolome analyses of plasma from wild-type and Nrf2 knockout mice collected at pre-flight, in-flight and post-flight time points, as well as tissues collected post-flight to clarify the metabolic responses during and after spaceflight and the contribution of Nrf2 to these responses. Plasma glycerophospholipid and sphingolipid levels were elevated during spaceflight, whereas triacylglycerol levels were lower after spaceflight. In wild-type mouse eWAT, triacylglycerol levels were increased, but phosphatidylcholine levels were decreased, and these changes were attenuated in Nrf2 knockout mice. Transcriptome analyses revealed marked changes in the expression of lipid-related genes in the liver and eWAT after spaceflight and the effects of Nrf2 knockout on these changes. Based on these results, we concluded that space stress provokes significant responses in lipid metabolism during and after spaceflight; Nrf2 plays critical roles in these responses.

  22. Gene expression changes related to bone mineralization, blood pressure and lipid metabolism in mouse kidneys after space travel Peer-reviewed

    Norio Suzuki, Yuma Iwamura, Taku Nakai, Koichiro Kato, Akihito Otsuki, Akira Uruno, Daisuke Saigusa, Keiko Taguchi, Mikiko Suzuki, Ritsuko Shimizu, Akane Yumoto, Risa Okada, Masaki Shirakawa, Dai Shiba, Satoru Takahashi, Takafumi Suzuki, Masayuki Yamamoto

    Kidney International　2021/11

    Publisher: Elsevier BV

    DOI： 10.1016/j.kint.2021.09.031 　

    ISSN： 0085-2538

  23. Blockade of the interaction between BMP9 and endoglin on erythroid progenitors promotes erythropoiesis in mice Peer-reviewed

    Ayami Yamaguchi, Ikuo Hirano, Shiho Narusawa, Kiyoshi Shimizu, Hiroyuki Ariyama, Kengo Yamawaki, Kenji Nagao, Masayuki Yamamoto, Ritsuko Shimizu

    Genes to Cells　2021/08/12

    Publisher: Wiley

    DOI： 10.1111/gtc.12887 　

    ISSN： 1356-9597

    eISSN： 1365-2443

  24. Nrf2 contributes to the weight gain of mice during space travel. International-journal Peer-reviewed

    Takafumi Suzuki, Akira Uruno, Akane Yumoto, Keiko Taguchi, Mikiko Suzuki, Nobuhiko Harada, Rie Ryoke, Eriko Naganuma, Nanae Osanai, Aya Goto, Hiromi Suda, Ryan Browne, Akihito Otsuki, Fumiki Katsuoka, Michael Zorzi, Takahiro Yamazaki, Daisuke Saigusa, Seizo Koshiba, Takashi Nakamura, Satoshi Fukumoto, Hironobu Ikehata, Keizo Nishikawa, Norio Suzuki, Ikuo Hirano, Ritsuko Shimizu, Tetsuya Oishi, Hozumi Motohashi, Hirona Tsubouchi, Risa Okada, Takashi Kudo, Michihiko Shimomura, Thomas W Kensler, Hiroyasu Mizuno, Masaki Shirakawa, Satoru Takahashi, Dai Shiba, Masayuki Yamamoto

    Communications biology　3　(1)　496-496　2020/09/08

    DOI： 10.1038/s42003-020-01227-2 　

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    Space flight produces an extreme environment with unique stressors, but little is known about how our body responds to these stresses. While there are many intractable limitations for in-flight space research, some can be overcome by utilizing gene knockout-disease model mice. Here, we report how deletion of Nrf2, a master regulator of stress defense pathways, affects the health of mice transported for a stay in the International Space Station (ISS). After 31 days in the ISS, all flight mice returned safely to Earth. Transcriptome and metabolome analyses revealed that the stresses of space travel evoked ageing-like changes of plasma metabolites and activated the Nrf2 signaling pathway. Especially, Nrf2 was found to be important for maintaining homeostasis of white adipose tissues. This study opens approaches for future space research utilizing murine gene knockout-disease models, and provides insights into mitigating space-induced stresses that limit the further exploration of space by humans.

  25. A non-mosaic transchromosomic mouse model of down syndrome carrying the long arm of human chromosome 21. International-journal Peer-reviewed

    Yasuhiro Kazuki, Feng J Gao, Yicong Li, Anna J Moyer, Benjamin Devenney, Kei Hiramatsu, Sachiko Miyagawa-Tomita, Satoshi Abe, Kanako Kazuki, Naoyo Kajitani, Narumi Uno, Shoko Takehara, Masato Takiguchi, Miho Yamakawa, Atsushi Hasegawa, Ritsuko Shimizu, Satoko Matsukura, Naohiro Noda, Narumi Ogonuki, Kimiko Inoue, Shogo Matoba, Atsuo Ogura, Liliana D Florea, Alena Savonenko, Meifang Xiao, Dan Wu, Denise As Batista, Junhua Yang, Zhaozhu Qiu, Nandini Singh, Joan T Richtsmeier, Takashi Takeuchi, Mitsuo Oshimura, Roger H Reeves

    eLife　9　2020/06/29

    DOI： 10.7554/eLife.56223 　

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    Animal models of Down syndrome (DS), trisomic for human chromosome 21 (HSA21) genes or orthologs, provide insights into better understanding and treatment options. The only existing transchromosomic (Tc) mouse DS model, Tc1, carries a HSA21 with over 50 protein coding genes (PCGs) disrupted. Tc1 is mosaic, compromising interpretation of results. Here, we "clone" the 34 MB long arm of HSA21 (HSA21q) as a mouse artificial chromosome (MAC). Through multiple steps of microcell-mediated chromosome transfer, we created a new Tc DS mouse model, Tc(HSA21q;MAC)1Yakaz ("TcMAC21"). TcMAC21 is not mosaic and contains 93% of HSA21q PCGs that are expressed and regulatable. TcMAC21 recapitulates many DS phenotypes including anomalies in heart, craniofacial skeleton and brain, molecular/cellular pathologies, and impairments in learning, memory and synaptic plasticity. TcMAC21 is the most complete genetic mouse model of DS extant and has potential for supporting a wide range of basic and preclinical research.

  26. Cohort Profile: Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study): rationale, progress and perspective. International-journal Peer-reviewed

    Shinichi Kuriyama, Hirohito Metoki, Masahiro Kikuya, Taku Obara, Mami Ishikuro, Chizuru Yamanaka, Masato Nagai, Hiroko Matsubara, Tomoko Kobayashi, Junichi Sugawara, Gen Tamiya, Atsushi Hozawa, Naoki Nakaya, Naho Tsuchiya, Tomohiro Nakamura, Akira Narita, Mana Kogure, Takumi Hirata, Ichiro Tsuji, Fuji Nagami, Nobuo Fuse, Tomohiko Arai, Yoshio Kawaguchi, Shinichi Higuchi, Masaki Sakaida, Yoichi Suzuki, Noriko Osumi, Keiko Nakayama, Kiyoshi Ito, Shinichi Egawa, Koichi Chida, Eiichi Kodama, Hideyasu Kiyomoto, Tadashi Ishii, Akito Tsuboi, Hiroaki Tomita, Yasuyuki Taki, Hiroshi Kawame, Kichiya Suzuki, Naoto Ishii, Soichi Ogishima, Satoshi Mizuno, Takako Takai-Igarashi, Naoko Minegishi, Jun Yasuda, Kazuhiko Igarashi, Ritsuko Shimizu, Masao Nagasaki, Osamu Tanabe, Seizo Koshiba, Hiroaki Hashizume, Hozumi Motohashi, Teiji Tominaga, Sadayoshi Ito, Kozo Tanno, Kiyomi Sakata, Atsushi Shimizu, Jiro Hitomi, Makoto Sasaki, Kengo Kinoshita, Hiroshi Tanaka, Tadao Kobayashi, Shigeo Kure, Nobuo Yaegashi, Masayuki Yamamoto

    International journal of epidemiology　49　(1)　18-19　2020/02/01

    DOI： 10.1093/ije/dyz169 　

    ISSN： 0300-5771

  27. Study profile of The Tohoku Medical Megabank Community-Based Cohort Study. Peer-reviewed

    Atsushi Hozawa, Kozo Tanno, Naoki Nakaya, Tomohiro Nakamura, Naho Tsuchiya, Takumi Hirata, Akira Narita, Mana Kogure, Kotaro Nochioka, Ryohei Sasaki, Nobuyuki Takanashi, Kotaro Otsuka, Kiyomi Sakata, Shinichi Kuriyama, Masahiro Kikuya, Osamu Tanabe, Junichi Sugawara, Kichiya Suzuki, Yoichi Suzuki, Eiichi N Kodama, Nobuo Fuse, Hideyasu Kiyomoto, Hiroaki Tomita, Akira Uruno, Yohei Hamanaka, Hirohito Metoki, Mami Ishikuro, Taku Obara, Tomoko Kobayashi, Kazuyuki Kitatani, Takako Takai-Igarashi, Soichi Ogishima, Mamoru Satoh, Hideki Ohmomo, Akito Tsuboi, Shinichi Egawa, Tadashi Ishii, Kiyoshi Ito, Sadayoshi Ito, Yasuyuki Taki, Naoko Minegishi, Naoto Ishii, Masao Nagasaki, Kazuhiko Igarashi, Seizo Koshiba, Ritsuko Shimizu, Gen Tamiya, Keiko Nakayama, Hozumi Motohashi, Jun Yasuda, Atsushi Shimizu, Tsuyoshi Hachiya, Yuh Shiwa, Teiji Tominaga, Hiroshi Tanaka, Kotaro Oyama, Ryoichi Tanaka, Hiroshi Kawame, Akimune Fukushima, Yasushi Ishigaki, Tomoharu Tokutomi, Noriko Osumi, Tadao Kobayashi, Fuji Nagami, Hiroaki Hashizume, Tomohiro Arai, Yoshio Kawaguchi, Shinichi Higuchi, Masaki Sakaida, Ryujin Endo, Satoshi Nishizuka, Ichiro Tsuji, Jiro Hitomi, Motoyuki Nakamura, Kuniaki Ogasawara, Nobuo Yaegashi, Kengo Kinoshita, Shigeo Kure, Akio Sakai, Seiichiro Kobayashi, Kenji Sobue, Makoto Sasaki, Masayuki Yamamoto

    Journal of epidemiology　31　(1)　65-76　2020/01/11

    DOI： 10.2188/jea.JE20190271 　

    ISSN： 0917-5040

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    BackgroundWe established a community-based cohort study to assess the long-term impact of the Great East Japan Earthquake on disaster victims and gene-environmental interactions on the incidence of major diseases such as cancer and cardiovascular diseases.MethodsWe asked participants to join our cohort in the health check-up settings and assessment center based settings. Inclusion criteria was aged 20 years or over and living in Miyagi or Iwate Prefecture. We obtained information on lifestyle, effect of disaster, blood, and urine information (Type 1 survey), and some detailed measurements (Type 2 survey), for example, carotid echography, calcaneal ultrasound bone mineral density, and so on. All participants agreed to measure genome information and to distribute their information widely.ResultsAs a result, 87,865 gave their informed consent to join our study. Participation rate at health check-up site was about 70%. The participants with Type 1 survey were more likely to have psychological distress than those of Type 2 survey, and women were more likely to have psychological distress than men. Additionally, coastal residents were more likely to have higher degrees of psychological distress than inland residents regardless of sex.ConclusionThis cohort comprised large sample size and it contains information on disaster, genome information, and metabolome information. This cohort also had several detailed measurements. Using this cohort enabled us to clarify the long-term effect of disaster and also to establish personalized prevention based on genome, metabolome, and other omics information.

  28. Oral Microbiome Analysis in Prospective Genome Cohort Studies of the Tohoku Medical Megabank Project. International-journal Peer-reviewed

    Sakae Saito, Yuichi Aoki, Toru Tamahara, Maki Goto, Hiroyuki Matsui, Junko Kawashima, Inaho Danjoh, Atsushi Hozawa, Shinichi Kuriyama, Yoichi Suzuki, Nobuo Fuse, Shigeo Kure, Riu Yamashita, Osamu Tanabe, Naoko Minegishi, Kengo Kinoshita, Akito Tsuboi, Ritsuko Shimizu, Masayuki Yamamoto

    Frontiers in cellular and infection microbiology　10　604596-604596　2020

    DOI： 10.3389/fcimb.2020.604596 　

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    A baseline oral microbiome study of the Tohoku Medical Megabank Organization (TMM) was planned to characterize the profile of the oral microbiome in the Japanese population. The study also aimed to clarify risk factors for multifactorial diseases by integrated analysis of the oral microbiome and host genome/omics information. From 2013 to 2016, we collected three types of oral biospecimens, saliva, supragingival plaque, and tongue swab, from a total of 25,101 participants who had a dental examination in TMM. In this study, we used two independent cohorts; the Community-Based Cohort and Birth and Three-Generation Cohort as discovery and validation cohorts, respectively, and we selected participants examined by a single dentist. We found through the 16S ribosomal RNA gene sequencing analysis of 834 participants of the Community-Based Cohort Study that there are differences in the microbial composition and community structure between saliva and plaque. The species diversities in both saliva and plaque were increased in correlation with the severity of periodontal disease. These results were nicely reproduced in the analysis of 455 participants of the Birth and Three-Generation Cohort Study. In addition, strong positive and negative associations of microbial taxa in both plaque and saliva with periodontitis-associated biofilm formation were detected by co-occurrence network analysis. The classes Actinobacteria and Bacilli, including oral health-associated bacterial species, showed a positive correlation in saliva. These results revealed differences in microbial composition and community structure between saliva and plaque and a correlation between microbial species and the severity of periodontal disease. We expect that the large database of the oral microbiome in the TMM biobank will help in the discovery of novel targets for the treatment and prevention of oral diseases, as well as for the discovery of therapeutic and/or preventive targets of systemic diseases.

  29. Design and Progress of Oral Health Examinations in the Tohoku Medical Megabank Project Peer-reviewed

    Akito Tsuboi, Hiroyuki Matsui, Naru Shiraishi, Takahisa Murakami, Akihito Otsuki, Junko Kawashima, Tomomi Kiyama, Toru Tamahara, Maki Goto, Shihoko Koyama, Junichi Sugawara, Eiichi N. Kodama, Hirohito Metoki, Atsushi Hozawa, Shinichi Kuriyama, Hiroaki Tomita, Masahiro Kikuya, Naoko Minegishi, Kichiya Suzuki, Seizo Koshiba, Gen Tamiya, Nobuo Fuse, Yuichi Aoki, Takako Takai-Igarashi, Soichi Ogishima, Tomohiro Nakamura, Mika Sakurai-Yageta, Fuji Nagami, Kengo Kinoshita, Shigeo Kure, Ritsuko Shimizu, Keiichi Sasaki, Masayuki Yamamoto

    The Tohoku Journal of Experimental Medicine　251　(2)　97-115　2020

    Publisher: Tohoku University Medical Press

    DOI： 10.1620/tjem.251.97 　

    ISSN： 0040-8727

    eISSN： 1349-3329

  30. Quantitative and qualitative impairments in GATA2 and myeloid neoplasms. Peer-reviewed

    Shimizu R, Yamamoto M

    IUBMB life　2019/11

    DOI： 10.1002/iub.2188 　

    ISSN： 1521-6543

  31. Establishment of Integrated Biobank for Precision Medicine and Personalized Healthcare: The Tohoku Medical Megabank Project. Peer-reviewed

    Fuse N, Sakurai-YagetaM, Katsuoka F, Danjoh I, Shimizu R, Tamiya G, Nagami F, Kawame H, Higuchi S, Kinoshita K, Kure S, Yamamoto M

    JMA Journal　2　(2)　113-122　2019/09

    DOI： 10.31662/jmaj.2019-0014. 　

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    The Tohoku Medical Megabank (TMM) project was established to provide creative reconstruction of the Tohoku area that suffered from a huge earthquake and ensuing tsunami (the Great East Japan Earthquake, GEJE). TMM aims to establish two large-scale genome cohorts and an integrated biobank managing biospecimen and related information. It supports community medicine by establishing next-generation medical systems through a combination of the prospective genome cohort studies with a total of 150,000 participants and genomic medicine. The strategies for genome analyses in TMM are to develop an elaborate genome reference panel by means of high-fidelity Japanese whole-genome sequence, to design custom single nucleotide polymorphism (SNP) arrays based on the reference panel, and to obtain genotype data for all the TMM cohort participants subsequently. Disease-associated genomic information and omics data, including metabolomics and microbiome analysis, provide an essential platform for precision medicine and personalized healthcare (PHC). Ethical, legal, and social issues (ELSI) and education are important for implementing genomic medicine. The major considerations of ELSI regarding each participant of the cohort studies are the respect for the autonomy and the protection of privacies. Moreover, developing and provide human resources not only for the TMM project but also for the social implementation of precision medicine and PHC is required. We started a pilot study of the return of genomic results for familial hypercholesterolemia (FH) as a target disease. TMM aims to establish solid platforms that support precision medicine and PHC based on the genomic and omics information and environmental and lifestyle factors of the individuals, which is one of the most advanced medical care beyond the evidenced-based medicine in the near future.

  32. Generation and Molecular Characterization of Human Ring Sideroblasts: a Key Role of Ferrous Iron in Terminal Erythroid Differentiation and Ring Sideroblast Formation. International-journal Peer-reviewed

    Saito K, Fujiwara T, Hatta S, Morita M, Ono K, Suzuki C, Fukuhara N, Onishi Y, Nakamura Y, Kawamata S, Shimizu R, Yamamoto M, Harigae H

    Molecular and cellular biology　39　(7)　2019/04

    DOI： 10.1128/MCB.00387-18 　

    ISSN： 0270-7306

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    Ring sideroblasts are a hallmark of sideroblastic anemia, although little is known about their characteristics. Here, we first generated mutant mice by disrupting the GATA-1 binding motif at the intron 1 enhancer of the ALAS2 gene, a gene responsible for X-linked sideroblastic anemia (XLSA). Although heterozygous female mice showed an anemic phenotype, ring sideroblasts were not observed in their bone marrow. We next established human induced pluripotent stem cell-derived proerythroblast clones harboring the same ALAS2 gene mutation. Through coculture with sodium ferrous citrate, mutant clones differentiated into mature erythroblasts and became ring sideroblasts with upregulation of metal transporters (MFRN1, ZIP8, and DMT1), suggesting a key role for ferrous iron in erythroid differentiation. Interestingly, holo-transferrin (holo-Tf) did not induce erythroid differentiation as well as ring sideroblast formation, and mutant cells underwent apoptosis. Despite massive iron granule content, ring sideroblasts were less apoptotic than holo-Tf-treated undifferentiated cells. Microarray analysis revealed upregulation of antiapoptotic genes in ring sideroblasts, a profile partly shared with erythroblasts from a patient with XLSA. These results suggest that ring sideroblasts exert a reaction to avoid cell death by activating antiapoptotic programs. Our model may become an important tool to clarify the pathophysiology of sideroblastic anemia.

  33. GATA2 hypomorphism induces chronic myelomonocytic leukemia in mice. Peer-reviewed

    Harada N, Hasegawa A, Hirano I, Yamamoto M, Shimizu R

    Cancer science　110　(4)　1183-1193　2019/04

    DOI： 10.1111/cas.13959 　

    ISSN： 1347-9032

  34. Genome analyses for the Tohoku Medical Megabank Project towards establishment of personalized healthcare. International-journal Peer-reviewed

    Jun Yasuda, Kengo Kinoshita, Fumiki Katsuoka, Inaho Danjoh, Mika Sakurai-Yageta, Ikuko N Motoike, Yoko Kuroki, Sakae Saito, Kaname Kojima, Matsuyuki Shirota, Daisuke Saigusa, Akihito Otsuki, Junko Kawashima, Yumi Yamaguchi-Kabata, Shu Tadaka, Yuichi Aoki, Takahiro Mimori, Kazuki Kumada, Jin Inoue, Satoshi Makino, Miho Kuriki, Nobuo Fuse, Seizo Koshiba, Osamu Tanabe, Masao Nagasaki, Gen Tamiya, Ritsuko Shimizu, Takako Takai-Igarashi, Soichi Ogishima, Atsushi Hozawa, Shinichi Kuriyama, Junichi Sugawara, Akito Tsuboi, Hideyasu Kiyomoto, Tadashi Ishii, Hiroaki Tomita, Naoko Minegishi, Yoichi Suzuki, Kichiya Suzuki, Hiroshi Kawame, Hiroshi Tanaka, Yasuyuki Taki, Nobuo Yaegashi, Shigeo Kure, Fuji Nagami, Kenjiro Kosaki, Yoichi Sutoh, Tsuyoshi Hachiya, Atsushi Shimizu, Makoto Sasaki, Masayuki Yamamoto

    Journal of biochemistry　165　(2)　139-158　2019/02/01

    DOI： 10.1093/jb/mvy096 　

    ISSN： 0021-924X

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    Personalized healthcare (PHC) based on an individual's genetic make-up is one of the most advanced, yet feasible, forms of medical care. The Tohoku Medical Megabank (TMM) Project aims to combine population genomics, medical genetics and prospective cohort studies to develop a critical infrastructure for the establishment of PHC. To date, a TMM CommCohort (adult general population) and a TMM BirThree Cohort (birth+three-generation families) have conducted recruitments and baseline surveys. Genome analyses as part of the TMM Project will aid in the development of a high-fidelity whole-genome Japanese reference panel, in designing custom single-nucleotide polymorphism (SNP) arrays specific to Japanese, and in estimation of the biological significance of genetic variations through linked investigations of the cohorts. Whole-genome sequencing from >3,500 unrelated Japanese and establishment of a Japanese reference genome sequence from long-read data have been done. We next aim to obtain genotype data for all TMM cohort participants (>150,000) using our custom SNP arrays. These data will help identify disease-associated genomic signatures in the Japanese population, while genomic data from TMM BirThree Cohort participants will be used to improve the reference genome panel. Follow-up of the cohort participants will allow us to test the genetic markers and, consequently, contribute to the realization of PHC.

  35. A Gata3 3' distal otic vesicle enhancer directs inner ear-specific Gata3 expression. International-journal Peer-reviewed

    Moriguchi T, Hoshino T, Rao A, Yu L, Takai J, Uemura S, Ise K, Nakamura Y, Lim KC, Shimizu R, Yamamoto M, Engel JD

    Molecular and cellular biology　28　(21)　e00302-18　2018/08

    DOI： 10.1128/MCB.00302-18 　

    ISSN： 0270-7306

    More details Close

    Transcription factor GATA3 plays vital roles in inner ear development, while regulatory mechanisms controlling its inner ear-specific expression are undefined. We demonstrate that a cis-regulatory element lying 571 kb 3' to the Gata3 gene directs inner ear-specific Gata3 expression, which we refer to as the Gata3 otic vesicle enhancer (OVE). In transgenic murine embryos, a 1.5-kb OVE-directed lacZ reporter (TgOVE-LacZ) exhibited robust lacZ expression specifically in the otic vesicle (OV), an inner ear primordial tissue, and its derivative semicircular canal. To further define the regulatory activity of this OVE, we generated Cre transgenic mice in which Cre expression was directed by a 246-bp core sequence within the OVE element (TgcoreOVE-Cre). TgcoreOVE-Cre successfully marked the OV-derived inner ear tissues, including cochlea, semicircular canal and spiral ganglion, when crossed with ROSA26 lacZ reporter mice. Furthermore, Gata3 conditionally mutant mice, when crossed with the TgcoreOVE-Cre, showed hypoplasia throughout the inner ear tissues. These results demonstrate that OVE has a sufficient regulatory activity to direct Gata3 expression specifically in the otic vesicle and semicircular canal and that Gata3 expression driven by the OVE is crucial for normal inner ear development.

  36. Effects of in vivo deletion of GATA2 in bone marrow stromal cells Peer-reviewed

    Shin Hasegawa, Tohru Fujiwara, Yoko Okitsu, Hiroki Kato, Yuki Sato, Noriko Fukuhara, Yasushi Onishi, Ritsuko Shimizu, Masayuki Yamamoto, Hideo Harigae

    EXPERIMENTAL HEMATOLOGY　56　31-45　2017/12

    DOI： 10.1016/j.exphem.2017.08.004 　

    ISSN： 0301-472X

    eISSN： 1873-2399

  37. Induction of erythropoietin gene expression in epithelial cells by chemicals identified in GATA inhibitor screenings Peer-reviewed

    Hiroshi Kaneko, Takehide Katoh, Ikuo Hirano, Atsushi Hasegawa, Tadayuki Tsujita, Masayuki Yamamoto, Ritsuko Shimizu

    GENES TO CELLS　22　(11)　939-952　2017/11

    DOI： 10.1111/gtc.12537 　

    ISSN： 1356-9597

    eISSN： 1365-2443

  38. Prolyl isomerase Pin1 promotes proplatelet formation of megakaryocytes via tau Peer-reviewed

    Taiki Shimizu, Chiyoko Uchida, Ritsuko Shimizu, Hozumi Motohashi, Takafumi Uchida

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　493　(2)　946-951　2017/11

    DOI： 10.1016/j.bbrc.2017.09.115 　

    ISSN： 0006-291X

    eISSN： 1090-2104

  39. Reducing Inflammatory Cytokine Production from Renal Collecting Duct Cells by Inhibiting GATA2 Ameliorates Acute Kidney Injury Peer-reviewed

    Lei Yu, Takashi Moriguchi, Hiroshi Kaneko, Makiko Hayashi, Atsushi Hasegawa, Masahiro Nezu, Hideyuki Saya, Masayuki Yamamoto, Ritsuko Shimizu

    MOLECULAR AND CELLULAR BIOLOGY　37　(22)　2017/11

    DOI： 10.1128/MCB.00211-17 　

    ISSN： 0270-7306

    eISSN： 1098-5549

  40. 【診断と治療のABC[125]貧血症】(第2章)病理・病態生理 転写因子異常に起因する血液疾患

    長谷川 敦史, 清水 律子

    最新医学　別冊　(貧血症)　34-42　2017/08

    Publisher: (株)最新医学社

    ISSN： 0370-8241

  41. Renal Anemia Model Mouse Established by Transgenic Rescue with an Erythropoietin Gene Lacking Kidney-Specific Regulatory Elements. International-journal Peer-reviewed

    Ikuo Hirano, Norio Suzuki, Shun Yamazaki, Hiroki Sekine, Naoko Minegishi, Ritsuko Shimizu, Masayuki Yamamoto

    Molecular and cellular biology　37　(4)　2017/02/15

    DOI： 10.1128/MCB.00451-16 　

    ISSN： 0270-7306

    More details Close

    The erythropoietin (Epo) gene is under tissue-specific inducible regulation. Because the kidney is the primary EPO-producing tissue in adults, impaired EPO production in chronic kidney disorders results in serious renal anemia. The Epo gene contains a liver-specific enhancer in the 3' region, but the kidney-specific enhancer for gene expression in renal EPO-producing (REP) cells remains elusive. Here, we examined a conserved upstream element for renal Epo regulation (CURE) region that spans 17.4 kb to 3.6 kb upstream of the Epo gene and harbors several phylogenetically conserved elements. We prepared various Epo gene-reporter constructs utilizing a bacterial artificial chromosome and generated a number of transgenic-mouse lines. We observed that deletion of the CURE region (δCURE) abrogated Epo gene expression in REP cells. Although transgenic expression of the δCURE construct rescued Epo-deficient mice from embryonic lethality, the rescued mice had severe EPO-dependent anemia. These mouse lines serve as an elaborate model for the search for erythroid stimulatory activity and are referred to as AnRED (anemic model with renal EPO deficiency) mice. We also dissected the CURE region by exploiting a minigene harboring four phylogenetically conserved elements in reporter transgenic-mouse analyses. Our analyses revealed that Epo gene regulation in REP cells is a complex process that utilizes multiple regulatory influences.

  42. GATA1 activity governed by configurations of cis-acting elements Invited Peer-reviewed

    Atsushi Hasegawa, Ritsuko Shimizu

    Frontiers in Oncology　6　269　2017/01/09

    Publisher: Frontiers Media S.A.

    DOI： 10.3389/fonc.2016.00269 　

    ISSN： 2234-943X

  43. 巨核球造血と血小板産生の新知見 3.巨核球造血の転写制御機構

    平野育生, 清水律子

    血液フロンティア　27　(6)　2017

    ISSN： 1344-6940

  44. Monitoring of minimal residual disease in early T-cell precursor acute lymphoblastic leukaemia by next-generation sequencing Peer-reviewed

    Xiaoqing Pan, Naoki Nariai, Noriko Fukuhara, Sakae Saito, Yukuto Sato, Fumiki Katsuoka, Kaname Kojima, Yoko Kuroki, Inaho Danjoh, Rumiko Saito, Shin Hasegawa, Yoko Okitsu, Aiko Kondo, Yasushi Onishi, Fuji Nagami, Hideyasu Kiyomoto, Atsushi Hozawa, Nobuo Fuse, Masao Nagasaki, Ritsuko Shimizu, Jun Yasuda, Hideo Harigae, Masayuki Yamamoto

    BRITISH JOURNAL OF HAEMATOLOGY　176　(2)　318-321　2017/01

    DOI： 10.1111/bjh.13948 　

    ISSN： 0007-1048

    eISSN： 1365-2141

  45. The Tohoku Medical Megabank Project: Design and Mission Peer-reviewed

    Shinichi Kuriyama, Nobuo Yaegashi, Fuji Nagami, Tomohiko Arai, Yoshio Kawaguchi, Noriko Osumi, Masaki Sakaida, Yoichi Suzuki, Keiko Nakayama, Hiroaki Hashizume, Gen Tamiya, Hiroshi Kawame, Kichiya Suzuki, Atsushi Hozawa, Naoki Nakaya, Masahiro Kikuya, Hirohito Metoki, Ichiro Tsuji, Nobuo Fuse, Hideyasu Kiyomoto, Junichi Sugawara, Akito Tsuboi, Shinichi Egawa, Kiyoshi Ito, Koichi Chida, Tadashi Ishii, Hiroaki Tomita, Yasuyuki Taki, Naoko Minegishi, Naoto Ishii, Jun Yasuda, Kazuhiko Igarashi, Ritsuko Shimizu, Masao Nagasaki, Seizo Koshiba, Kengo Kinoshita, Soichi Ogishima, Takako Takai-Igarashi, Teiji Tominaga, Osamu Tanabe, Noriaki Ohuchi, Toru Shimosegawa, Shigeo Kure, Hiroshi Tanaka, Sadayoshi Ito, Jiro Hitomi, Kozo Tanno, Motoyuki Nakamura, Kuniaki Ogasawara, Seiichiro Kobayashi, Kiyomi Sakata, Mamoru Satoh, Atsushi Shimizu, Makoto Sasaki, Ryujin Endo, Kenji Sobue, Masayuki Yamamoto

    JOURNAL OF EPIDEMIOLOGY　26　(9)　493-511　2016/09

    DOI： 10.2188/jea.JE20150268 　

    ISSN： 0917-5040

  46. GATA1 Binding Kinetics on Conformation-Specific Binding Sites Elicit Differential Transcriptional Regulation Peer-reviewed

    Atsushi Hasegawa, Hiroshi Kaneko, Daishi Ishihara, Masahiro Nakamura, Akira Watanabe, Masayuki Yamamoto, Cecelia D. Trainor, Ritsuko Shimizu

    MOLECULAR AND CELLULAR BIOLOGY　36　(16)　2151-2167　2016/08

    DOI： 10.1128/MCB.00017-16 　

    ISSN： 0270-7306

    eISSN： 1098-5549

  47. GATA-related hematologic disorders Invited Peer-reviewed

    Ritsuko Shimizu, Masayuki Yamamoto

    EXPERIMENTAL HEMATOLOGY　44　(8)　696-705　2016/08

    DOI： 10.1016/j.exphem.2016.05.010 　

    ISSN： 0301-472X

    eISSN： 1873-2399

  48. GATA2 regulates dendritic cell differentiation Peer-reviewed

    Koichi Onodera, Tohru Fujiwara, Yasushi Onishi, Ari Itoh-Nakadai, Yoko Okitsu, Noriko Fukuhara, Kenichi Ishizawa, Ritsuko Shimizu, Masayuki Yamamoto, Hideo Harigae

    BLOOD　128　(4)　508-518　2016/07

    DOI： 10.1182/blood-2016-02-698118 　

    ISSN： 0006-4971

    eISSN： 1528-0020

  49. Unique cistrome defined as CsMBE is strictly required for Nrf2-sMaf heterodimer function in cytoprotection Peer-reviewed

    Akihito Otsuki, Mikiko Suzuki, Fumiki Katsuoka, Kouhei Tsuchida, Hiromi Suda, Masanobu Morita, Ritsuko Shimizu, Masayuki Yamamoto

    FREE RADICAL BIOLOGY AND MEDICINE　91　45-57　2016/02

    DOI： 10.1016/j.freeradbiomed.2015.12.005 　

    ISSN： 0891-5849

    eISSN： 1873-4596

  50. Phylogeny and Ontogeny of Erythropoiesis Peer-reviewed

    Wataru Nunomura, Aurora M. Cianciarullo, Takashi Kato, Ritsuko Shimizu, Malgorzata Witeska

    BIOMED RESEARCH INTERNATIONAL　2015　136270　2015

    DOI： 10.1155/2015/136270 　

    ISSN： 2314-6133

    eISSN： 2314-6141

  51. GATA2 regulates differentiation of bone marrow-derived mesenchymal stem cells Peer-reviewed

    Mayumi Kamata, Yoko Okitsu, Tohru Fujiwara, Masahiko Kanehira, Shinji Nakajima, Taro Takahashi, Ai Inoue, Noriko Fukuhara, Yasushi Onishi, Kenichi Ishizawa, Ritsuko Shimizu, Masayuki Yamamoto, Hideo Harigae

    HAEMATOLOGICA　99　(11)　1686-1696　2014/11

    DOI： 10.3324/haematol.2014.105692 　

    ISSN： 0390-6078

  52. Conformational Change in Transfer RNA Is an Early Indicator of Acute Cellular Damage Peer-reviewed

    Eikan Mishima, Chisako Inoue, Daisuke Saigusa, Ryusuke Inoue, Koki Ito, Yusuke Suzuki, Daisuke Jinno, Yuri Tsukui, Yosuke Akamatsu, Masatake Araki, Kimi Araki, Ritsuko Shimizu, Haruka Shinke, Takehiro Suzuki, Yoichi Takeuchi, Hisato Shima, Yasutoshi Akiyama, Takafumi Toyohara, Chitose Suzuki, Yoshikatu Saiki, Teiji Tominaga, Shigehito Miyagi, Naoki Kawagisihi, Tomoyoshi Soga, Takayoshi Ohkubo, Kenichi Yamamura, Yutaka Imai, Satohiro Masuda, Venkata Sabbisetti, Takaharu Ichimura, David B. Mount, Joseph V. Bonventre, Sadayoshi Ito, Yoshihisa Tomioka, Kunihiko Itoh, Takaaki Abe

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　25　(10)　2316-2326　2014/10

    DOI： 10.1681/ASN.2013091001 　

    ISSN： 1046-6673

    eISSN： 1533-3450

  53. Down syndrome-associated haematopoiesis abnormalities created by chromosome transfer and genome editing technologies Peer-reviewed

    Yasuhiro Kazuki, Yuwna Yakura, Satoshi Abe, Mitsuhiko Osaki, Naoyo Kajitani, Kanako Kazuki, Shoko Takehara, Kazuhisa Honma, Hirofumi Suemori, Satoshi Yamazaki, Tetsushi Sakuma, Tsutomu Toki, Ritsuko Shimizu, Hiromitsu Nakauchi, Takashi Yamamoto, Mitsuo Oshimura

    SCIENTIFIC REPORTS　4　6136　2014/08

    DOI： 10.1038/srep06136 　

    ISSN： 2045-2322

  54. PGC-1 Coactivator Activity Is Required for Murine Erythropoiesis Peer-reviewed

    Shuaiying Cui, Osamu Tanabe, Kim-Chew Lim, H. Eric Xu, X. Edward Zhou, Jiandie D. Lin, Lihong Shi, Lindsay Schmidt, Andrew Campbell, Ritsuko Shimizu, Masayuki Yamamoto, James Douglas Engel

    MOLECULAR AND CELLULAR BIOLOGY　34　(11)　1956-1965　2014/06

    DOI： 10.1128/MCB.00247-14 　

    ISSN： 0270-7306

    eISSN： 1098-5549

  55. A Remote GATA2 Hematopoietic Enhancer Drives Leukemogenesis in inv(3)(q21;q26) by Activating EVI1 Expression Peer-reviewed

    Hiromi Yamazaki, Mikiko Suzuki, Akihito Otsuki, Ritsuko Shimizu, Emery H. Bresnick, James Douglas Engel, Masayuki Yamamoto

    CANCER CELL　25　(4)　415-427　2014/04

    DOI： 10.1016/j.ccr.2014.02.008 　

    ISSN： 1535-6108

    eISSN： 1878-3686

  56. Keap1-Nrf2 system regulates cell fate determination of hematopoietic stem cells Peer-reviewed

    Shohei Murakami, Ritsuko Shimizu, Paul-Henri Romeo, Masayuki Yamamoto, Hozumi Motohashi

    GENES TO CELLS　19　(3)　239-253　2014/03

    DOI： 10.1111/gtc.12126 　

    ISSN： 1356-9597

    eISSN： 1365-2443

  57. 赤血球造血の基礎と臨床 4.赤血球分化の決定機構

    清水律子

    血液フロンティア　24　(4)　2014

    ISSN： 1344-6940

  58. GATA factor switching from GATA2 to GATA1 contributes to erythroid differentiation Peer-reviewed

    Mikiko Suzuki, Maki Kobayashi-Osaki, Shuichi Tsutsumi, Xiaoqing Pan, Shin'ya Ohmori, Jun Takai, Takashi Moriguchi, Osamu Ohneda, Kinuko Ohneda, Ritsuko Shimizu, Yasuharu Kanki, Tatsuhiko Kodama, Hiroyuki Aburatani, Masayuki Yamamoto

    GENES TO CELLS　18　(11)　921-933　2013/11

    DOI： 10.1111/gtc.12086 　

    ISSN： 1356-9597

    eISSN： 1365-2443

  59. Verification of the in vivo activity of three distinct cis-acting elements within the Gata1 gene promoter-proximal enhancer in mice Peer-reviewed

    Ritsuko Shimizu, Atsushi Hasegawa, Sergio Ottolenghi, Antonella Ronchi, Masayuki Yamamoto

    GENES TO CELLS　18　(11)　1032-1041　2013/11

    DOI： 10.1111/gtc.12096 　

    ISSN： 1356-9597

    eISSN： 1365-2443

  60. Loss of a Rho-Regulated Actin Nucleator, mDia2, Impairs Cytokinesis during Mouse Fetal Erythropoiesis Peer-reviewed

    Sadanori Watanabe, Tihana De Zan, Toshimasa Ishizaki, Shingo Yasuda, Hiroshi Kamijo, Daisuke Yamada, Tomohiro Aoki, Hiroshi Kiyonari, Hiroshi Kaneko, Ritsuko Shimizu, Masayuki Yamamoto, Gohta Goshima, Shuh Narumiya

    CELL REPORTS　5　(4)　926-932　2013/11

    DOI： 10.1016/j.celrep.2013.10.021 　

    ISSN： 2211-1247

  61. Establishment of erythroleukemic GAK14 cells and characterization of GATA1 N-terminal domain Peer-reviewed

    Harumi Y. Mukai, Mikiko Suzuki, Masumi Nagano, Shin'ya Ohmori, Akihito Otsuki, Kouhei Tsuchida, Takashi Moriguchi, Kinuko Ohneda, Ritsuko Shimizu, Osamu Ohneda, Masayuki Yamamoto

    Genes to Cells　18　(10)　886-898　2013/10

    DOI： 10.1111/gtc.12084 　

    ISSN： 1356-9597 1365-2443

  62. Hes repressors are essential regulators of hematopoietic stem cell development downstream of notch signaling Peer-reviewed

    Jordi Guiu, Ritsuko Shimizu, Teresa D'Altri, Stuart T. Fraser, Jun Hatakeyama, Emery H. Bresnick, Ryoichiro Kageyama, Elaine Dzierzak, Masayuki Yamamoto, Lluis Espinosa, Anna Bigas

    Journal of Experimental Medicine　210　(1)　71-84　2013/01

    DOI： 10.1084/jem.20120993 　

    ISSN： 0022-1007 1540-9538

  63. Naturally occurring oncogenic GATA1 mutants with internal deletions in transient abnormal myelopoiesis in Down syndrome Peer-reviewed

    Tsutomu Toki, Rika Kanezaki, Eri Kobayashi, Hiroshi Kaneko, Mikiko Suzuki, RuNan Wang, Kiminori Terui, Hirokazu Kanegane, Miho Maeda, Mikiya Endo, Tatsuki Mizuochi, Souichi Adachi, Yasuhide Hayashi, Masayuki Yamamoto, Ritsuko Shimizu, Etsuro Ito

    Blood　121　(16)　3181-3184　2013

    Publisher: American Society of Hematology

    DOI： 10.1182/blood-2012-01-405746 　

    ISSN： 1528-0020 0006-4971

  64. Contribution of GATA1 dysfunction to multi-step leukemogenesis Invited Peer-reviewed

    Ritsuko Shimizu, Masayuki Yamamoto

    Cancer Science　103　(12)　2039-2044　2012/12

    DOI： 10.1111/cas.12007 　

    ISSN： 1347-9032 1349-7006

  65. UG4 Enhancer-Driven GATA-2 and Bone Morphogenetic Protein 4 Complementation Remedies the CAKUT Phenotype in Gata2 Hypomorphic Mutant Mice Peer-reviewed

    Keiko Ainoya, Takashi Moriguchi, Shin'ya Ohmori, Tomokazu Souma, Jun Takai, Masanobu Morita, Kelly J. Chandler, Douglas P. Mortlock, Ritsuko Shimizu, James Douglas Engel, Kim-Chew Lim, Masayuki Yamamoto

    MOLECULAR AND CELLULAR BIOLOGY　32　(12)　2312-2322　2012/06

    DOI： 10.1128/MCB.06699-11 　

    ISSN： 0270-7306

  66. N- and C-terminal Transactivation Domains of GATA1 Protein Coordinate Hematopoietic Program Peer-reviewed

    Hiroshi Kaneko, Eri Kobayashi, Masayuki Yamamoto, Ritsuko Shimizu

    JOURNAL OF BIOLOGICAL CHEMISTRY　287　(25)　21439-21449　2012/06

    DOI： 10.1074/jbc.M112.370437 　

    ISSN： 0021-9258

  67. Mature erythrocyte membrane homeostasis is compromised by loss of the GATA1-FOG1 interaction Peer-reviewed

    Atsushi Hasegawa, Ritsuko Shimizu, Narla Mohandas, Masayuki Yamamoto

    BLOOD　119　(11)　2615-2623　2012/03

    DOI： 10.1182/blood-2011-09-382473 　

    ISSN： 0006-4971

  68. Protective role of Nrf2 in age-related hearing loss and gentamicin ototoxicity Peer-reviewed

    Tomofumi Hoshino, Keiji Tabuchi, Bungo Nishimura, Shuho Tanaka, Masahiro Nakayama, Tetsuro Ishii, Eiji Warabi, Toru Yanagawa, Ritsuku Shimizu, Masayuki Yamamoto, Akira Hara

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　415　(1)　94-98　2011/11

    DOI： 10.1016/j.bbrc.2011.10.019 　

    ISSN： 0006-291X

  69. The Ufm1-activating enzyme Uba5 is indispensable for erythroid differentiation in mice Peer-reviewed

    Kanako Tatsumi, Harumi Yamamoto-Mukai, Ritsuko Shimizu, Satoshi Waguri, Yu-Shin Sou, Ayako Sakamoto, Choji Taya, Hiroshi Shitara, Takahiko Hara, Chin Ha Chung, Keiji Tanaka, Masayuki Yamamoto, Masaaki Komatsu

    NATURE COMMUNICATIONS　2　181-181　2011/02

    DOI： 10.1038/ncomms1182 　

    ISSN： 2041-1723

  70. Transcriptional regulation by GATA1 and GATA2 during erythropoiesis Invited Peer-reviewed

    Mikiko Suzuki, Ritsuko Shimizu, Masayuki Yamamoto

    INTERNATIONAL JOURNAL OF HEMATOLOGY　93　(2)　150-155　2011/02

    DOI： 10.1007/s12185-011-0770-6 　

    ISSN： 0925-5710

  71. Nrf2 and selenoproteins are essential for maintaining oxidative homeostasis in erythrocytes and protecting against hemolytic anemia Peer-reviewed

    Yukie Kawatani, Takafumi Suzuki, Ritsuko Shimizu, Vincent P. Kelly, Masayuki Yamamoto

    BLOOD　117　(3)　986-996　2011/01

    DOI： 10.1182/blood-2010-05-285817 　

    ISSN： 0006-4971

  72. Dual-Color Luciferase Mouse Directly Demonstrates Coupled Expression of Two Clock Genes Peer-reviewed

    Takako Noguchi, Tomoko Michihata, Wataru Nakamura, Toru Takumi, Ritsuko Shimizu, Masayuki Yamamoto, Masaaki Ikeda, Yoshihiro Ohmiya, Yoshihiro Nakajima

    BIOCHEMISTRY　49　(37)　8053-8061　2010/09

    DOI： 10.1021/bi100545h 　

    ISSN： 0006-2960

  73. GATA factor switching during erythroid differentiation Invited Peer-reviewed

    Hiroshi Kaneko, Ritsuko Shimizu, Masayuki Yamamoto

    CURRENT OPINION IN HEMATOLOGY　17　(3)　163-168　2010/05

    DOI： 10.1097/MOH.0b013e32833800b8 　

    ISSN： 1065-6251

  74. Loss of the Gata1 Gene IE Exon Leads to Variant Transcript Expression and the Production of a GATA1 Protein Lacking the N-terminal Domain Peer-reviewed

    Eri Kobayashi, Ritsuko Shimizu, Yuko Kikuchi, Satoru Takahashi, Masayuki Yamamoto

    JOURNAL OF BIOLOGICAL CHEMISTRY　285　(1)　773-783　2010/01

    DOI： 10.1074/jbc.M109.030726 　

    ISSN： 0021-9258

  75. Induction of hyperproliferative fetal megakaryopoiesis by an N-terminally truncated GATA1 mutant Peer-reviewed

    Ritsuko Shimizu, Eri Kobayashi, James Douglas Engel, Masayuki Yamamoto

    GENES TO CELLS　14　(9)　1119-1131　2009/09

    DOI： 10.1111/j.1365-2443.2009.01338.x 　

    ISSN： 1356-9597

  76. Direct Binding of pRb/E2F-2 to GATA-1 Regulates Maturation and Terminal Cell Division during Erythropoiesis Peer-reviewed

    Zahra Kadri, Ritsuko Shimizu, Osamu Ohneda, Leila Maouche-Chretien, Sylvie Gisselbrecht, Masayuki Yamamoto, Paul-Henri Romeo, Philippe Leboulch, Stany Chretien

    PLOS BIOLOGY　7　(6)　e1000123-e1000123　2009/06

    DOI： 10.1371/journal.pbio.1000123 　

    ISSN： 1544-9173

  77. Stem cells of GATA1-related leukemia undergo pernicious changes after 5-fluorouracil treatment. International-journal Peer-reviewed

    Kanako Abe, Ritsuko Shimizu, Xiaoqing Pan, Hiromi Hamada, Hiroyuki Yoshikawa, Masayuki Yamamoto

    Experimental hematology　37　(4)　435-445　2009/04

    DOI： 10.1016/j.exphem.2008.12.004 　

    ISSN： 0301-472X

  78. Leukemia-related transcription factor TEL/ETV6 expands erythroid precursors and stimulates hemoglobin synthesis Peer-reviewed

    Minenori Eguchi-Ishimae, Mariko Eguchi, Kazuhiro Maki, Catherine Porcher, Ritsuko Shimizu, Masayuki Yamamoto, Kinuko Mitani

    CANCER SCIENCE　100　(4)　689-697　2009/04

    DOI： 10.1111/j.1349-7006.2009.01097.x 　

    ISSN： 1347-9032

  79. GATA1関連白血病

    清水律子

    東北医学雑誌　121　(2)　2009

    ISSN： 0040-8700

  80. GATA1 - related leukaemias Invited Peer-reviewed

    Ritsuko Shimizu, James Douglas Engel, Masayuki Yamamoto

    NATURE REVIEWS CANCER　8　(4)　279-287　2008/04

    DOI： 10.1038/nrc2348 　

    ISSN： 1474-175X

  81. Reduced BMP4 abundance in Gata2 hypomorphic mutant mice result in uropathies resembling human CAKUT Peer-reviewed

    Tomofumi Hoshino, Ritsuko Shimizu, Shinya Ohmori, Masumi Nagano, Xiaoqing Pan, Osamu Ohneda, Melin Khandekar, Masayuki Yamamoto, Kim-Chew Lim, James Douglas Engel

    GENES TO CELLS　13　(2)　159-170　2008/02

    DOI： 10.1111/j.1365-2443.2007.01158.x 　

    ISSN： 1356-9597

  82. Impairment of erythroid and megakaryocytic differentiation by a leukemia-associated and t(9;9)-derived fusion gene product, SET/TAF-I beta-CAN/NUp214 Peer-reviewed

    Shoko Saito, Kaoru Nouno, Ritsuko Shimizu, Masayuki Yamamoto, Kyosuke Nagata

    JOURNAL OF CELLULAR PHYSIOLOGY　214　(2)　322-333　2008/02

    DOI： 10.1002/jcp.21199 　

    ISSN： 0021-9541

  83. Leukemogenesis related to GATA-1 mutation

    安部加奈子, 清水律子, 山本雅之

    日本産婦人科・新生児血液学会誌　17　(2)　2008

    ISSN： 0916-8796

  84. In vivo promoter analysis on refeeding response of hepatic sterol regulatory element-binding protein-1c expression Peer-reviewed

    Yoshinori Takeuchi, Naoya Yahagi, Yoshimi Nakagawa, Takashi Matsuzaka, Ritsuko Shimizu, Motohiro Sekiya, Yoko Iizuka, Ken Ohashi, Takanari Gotoda, Masayuki Yamamoto, Ryozo Nagai, Takashi Kadowaki, Nobuhiro Yamada, Jun-ichi Osuga, Hitoshi Shimano

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　363　(2)　329-335　2007/11

    DOI： 10.1016/j.bbrc.2007.08.165 　

    ISSN： 0006-291X

    eISSN： 1090-2104

  85. Function and gene expression regulation of GATA-1 and GATA-2 transcription Peer-reviewed

    Ritsuko Shimizu, Masayuki Yamamoto

    SEIKAGAKU　79　(10)　941-952　2007/10

    ISSN： 0037-1017

  86. Dynamic regulation of Gata factor levels is more important than their identity Peer-reviewed

    Rita Ferreira, Albert Wai, Ritsuko Shimizu, Nynke Gillemans, Robbert Rottier, Marieke von Lindern, Kinuko Ohneda, Frank Grosveld, Masayuki Yamamoto, Sjaak Philipsen

    BLOOD　109　(12)　5481-5490　2007/06

    DOI： 10.1182/blood-2006-11-060491 　

    ISSN： 0006-4971

    eISSN： 1528-0020

  87. A Gata2 intronic enhancer confers its pan-endothelia-specific regulation Peer-reviewed

    Melin Khandekar, William Brandt, Yinghui Zhou, Susan Dagenais, Thomas W. Glover, Norio Suzuki, Ritsuko Shimizu, Masayuki Yamamoto, Kim-Chew Lim, James Douglas Engel

    DEVELOPMENT　134　(9)　1703-1712　2007/05

    DOI： 10.1242/dev.001297 　

    ISSN： 0950-1991

  88. GATA-1 self-association controls erythroid development in vivo Peer-reviewed

    Ritsuko Shimizu, Cecelia D. Trainor, Keizo Nishikawa, Makoto Kobayashi, Kinuko Ohneda, Masayuki Yamamoto

    JOURNAL OF BIOLOGICAL CHEMISTRY　282　(21)　15862-15871　2007/05

    DOI： 10.1074/jbc.M701936200 　

    ISSN： 0021-9258

  89. Characterization of GATA-1(+) hemangioblastic cells in the mouse embryo Peer-reviewed

    Tomomasa Yokomizo, Satoru Takahashi, Naomi Mochizuki, Takashi Kuroha, Masatsugu Ema, Asami Wakamatsu, Ritsuko Shimizu, Osamu Ohneda, Motomi Osato, Hitoshi Okada, Toshihisa Komori, Minetaro Ogawa, Shin-Ichi Nishikawa, Yoshiaki Ito, Masayuki Yamamoto

    EMBO JOURNAL　26　(1)　184-196　2007/01

    DOI： 10.1038/sj.emboj.7601480 　

    ISSN： 0261-4189

    eISSN： 1460-2075

  90. 白血病の分子病態-最近の進歩 GATA-1の機能異常と白血病-発現低下と構造異常-

    安部加奈子, 清水律子

    月刊血液・腫よう科　52　(6)　2006

    ISSN： 0915-8529

  91. Rapid turnover of GATA-2 via ubiquitin-proteasome protein degradation pathway Peer-reviewed

    N Minegishi, N Suzuki, Y Kawatani, R Shimizu, M Yamamoto

    GENES TO CELLS　10　(7)　693-704　2005/07

    DOI： 10.1111/j.1365-2443.2005.00864.x 　

    ISSN： 1356-9597

  92. Graded levels of GATA-1 expression modulate survival, proliferation, and differentiation of erythroid progenitors Peer-reviewed

    XQ Pan, O Ohnedal, K Ohneda, F Lindeboom, F Iwata, R Shimizu, M Nagano, N Suwabe, S Philipsen, KC Lim, JD Engel, M Yamamoto

    JOURNAL OF BIOLOGICAL CHEMISTRY　280　(23)　22385-22394　2005/06

    DOI： 10.1074/jbc.M500081200 　

    ISSN： 0021-9258

  93. Gene expression regulation and domain function of hematopoietic GATA factors Invited Peer-reviewed

    R Shimizu, M Yamamoto

    SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY　16　(1)　129-136　2005/02

    DOI： 10.1016/j.semcdb.2004.11.001 　

    ISSN： 1084-9521

  94. Transgenic over-expression of GATA-1 mutant lacking N-finger domain causes hemolytic syndrome in mouse erythroid cells Peer-reviewed

    M Nakano, K Ohneda, H Yamamoto-Mukai, R Shimizu, O Ohneda, S Ohmura, M Suzuki, S Tsukamoto, T Yanagawa, H Yoshida, Y Takakuwa, M Yamamoto

    GENES TO CELLS　10　(1)　47-62　2005/01

    DOI： 10.1111/j.1365-2443.2005.00814.x 　

    ISSN： 1356-9597

  95. Leukemogenesis caused by incapacitated GATA-1 function Peer-reviewed

    R Shimizu, T Kuroha, O Ohneda, XQ Pan, K Ohneda, S Takahashi, S Philipsen, M Yamamoto

    MOLECULAR AND CELLULAR BIOLOGY　24　(24)　10814-10825　2004/12

    DOI： 10.1128/MCB.24.24.10814-10825.2004 　

    ISSN： 0270-7306

  96. Transgenic rescue of GATA-1-deficient mice with GATA-1 lacking a FOG-1 association site phenocopies patients with X-linked thrombocytopenia Peer-reviewed

    R Shimizu, K Ohneda, JD Engel, CD Trainor, M Yamamoto

    BLOOD　103　(7)　2560-2567　2004/04

    DOI： 10.1182/blood-2003-07-2514 　

    ISSN： 0006-4971

  97. モデルマウスが教える造血制御と白血病発症 白血病発症(1)GATA-1ノックダウンマウス

    清水律子, 山本雅之

    Mebio　21　(8)　2004

    ISSN： 0910-0474

  98. A minigene containing four discrete cis elements recapitulates GATA-1 gene expression in vivo Peer-reviewed

    K Ohneda, R Shimizu, S Nishimura, Y Muraosa, S Takahashi, JD Engel, M Yamamoto

    GENES TO CELLS　7　(12)　1243-1254　2002/12

    DOI： 10.1046/j.1365-2443.2002.00595.x 　

    ISSN： 1356-9597

  99. Elimination of Pasteurella pneumotropica from a contaminated mouse colony by oral administration of enrofloxacin Peer-reviewed

    Y Ueno, R Shimizu, R Nozu, S Takahashi, M Yamamoto, F Sugiyama, A Takakura, T Itoh, K Yagami

    EXPERIMENTAL ANIMALS　51　(4)　401-405　2002/07

    DOI： 10.1538/expanim.51.401 　

    ISSN： 1341-1357

  100. Essential and instructive roles of GATA factors in eosinophil development Peer-reviewed

    R Hirasawa, R Shimizu, S Takahashi, M Osawa, S Takayanagi, Y Kato, M Onodera, N Minegishi, M Yamamoto, K Fukao, H Taniguchi, H Nakauchi, A Iwama

    JOURNAL OF EXPERIMENTAL MEDICINE　195　(11)　1379-1386　2002/06

    DOI： 10.1084/jem.20020170 　

    ISSN： 0022-1007

  101. A functional role of Stat3 in in vivo megakaryopoiesis Invited Peer-reviewed

    K Kirito, M Osawa, H Morita, R Shimizu, M Yamamoto, A Oda, H Fujita, M Tanaka, K Nakajima, Y Miura, K Ozawa, N Komatsu

    BLOOD　99　(9)　3220-3227　2002/05

    DOI： 10.1182/blood.V99.9.3220 　

    ISSN： 0006-4971

  102. Effect of growth factors on ex vivo bone marrow cell expansion using three-dimensional matrix support Peer-reviewed

    T Tun, H Miyoshi, T Aung, S Takahashi, R Shimizu, T Kuroha, M Yamamoto, N Ohshima

    ARTIFICIAL ORGANS　26　(4)　333-339　2002/04

    DOI： 10.1046/j.1525-1594.2002.06842.x 　

    ISSN： 0160-564X

  103. In vivo requirements for GATA-1 functional domains during primitive and definitive erythropoiesis Peer-reviewed

    R Shimizu, S Takahashi, K Ohneda, JD Engel, M Yamamoto

    EMBO JOURNAL　20　(18)　5250-5260　2001/09

    DOI： 10.1093/emboj/20.18.5250 　

    ISSN： 0261-4189

  104. 遺伝子改変マウスを用いた血液疾患病態の解明

    山本雅之, 清水律子

    臨床血液　42　(4)　2001

    ISSN： 0485-1439

  105. モデルマウス 10 MDSモデルマウス

    清水律子

    分子細胞治療　2　(6)　2001

    ISSN： 1345-2266

  106. A functional role of mitogen-activated protein kinases, Erk1 and Erk2, in the differentiation of a human leukemia cell line, UT-7/GM: A possible key factor for cell fate determination toward erythroid and megakaryocytic lineages Peer-reviewed

    M Uchida, K Kirito, R Shimizu, Y Miura, K Ozawa, N Komatsu

    INTERNATIONAL JOURNAL OF HEMATOLOGY　73　(1)　78-83　2001/01

    ISSN： 0925-5710

  107. GATA factor transgenes under GATA-1 locus control rescue germline GATA-1 mutant deficiencies Peer-reviewed

    S Takahashi, R Shimizu, N Suwabe, T Kuroha, K Yoh, J Ohta, S Nishimura, KC Lim, JD Engel, M Yamamoto

    BLOOD　96　(3)　910-916　2000/08

    ISSN： 0006-4971

  108. 特発性血小板減少性紫斑病に対するプレドニゾロン少量療法 Peer-reviewed

    大嶺謙, 和泉透, 室井一男, 清水律子, 今川重彦, 小松則夫, 佐々木龍平, 畠清彦, 三浦恭定, 小澤敬也

    臨床血液　41　(1)　8-11　2000/01

    Publisher:

    DOI： 10.11406/rinketsu.41.8 　

    ISSN： 0485-1439

  109. Dominant negative effect of a truncated erythropoietin receptor (EPOR-T) on erythropoietin-induced erythroid differentiation: Possible involvement of EPOR-T in ineffective erythropoiesis of myelodysplastic syndrome Peer-reviewed

    R Shimizu, N Komatsu, Y Miura

    EXPERIMENTAL HEMATOLOGY　27　(2)　229-233　1999/02

    DOI： 10.1016/S0301-472X(98)00048-4 　

    ISSN： 0301-472X

  110. [Retrospective analysis of elderly patients > or = 60 years of age with acute leukemia]. Peer-reviewed

    Tabata M, Yoshida M, Izumi T, Kawano C, Kuribara R, Toshima M, Omine K, Takatoku M, Uchida M, Kirito K, Miyazato A, Takahashi H, Hoshino M, Terui Y, Tomizuka H, Otsuki T, Shimizu R, Tsunoda J, Muroi K, Furukawa Y, Amemiya Y, Imagawa S, Komatsu N, Suzuki T, Miura Y

    Rinsho Ketsueki　39　(3)　176-184　1998/03

    Publisher:

    DOI： 10.11406/rinketsu.39.176 　

    ISSN： 0485-1439

  111. In vitro development of erythroid and megakaryocytic cells from a UT-7 subline, UT-7/GM Peer-reviewed

    N Komatsu, K Kirito, R Shimizu, M Kunitama, M Yamada, M Uchida, M Takatoku, M Eguchi, Y Miura

    BLOOD　89　(11)　4021-4033　1997/06

    ISSN： 0006-4971

  112. Tec protein-tyrosine kinase is involved in the thrombopoietin/c-Mpl signaling pathway Peer-reviewed

    Y Yamashita, A Miyazato, R Shimizu, N Komatsu, Y Miura, K Ozawa, H Mano

    EXPERIMENTAL HEMATOLOGY　25　(3)　211-216　1997/03

    ISSN： 0301-472X

  113. Identification of functional domains of the human thrombopoietin receptor required for growth and differentiation of megakaryocytic cells Peer-reviewed

    M Takatoku, M Kametaka, R Shimizu, Y Miura, N Komatsu

    JOURNAL OF BIOLOGICAL CHEMISTRY　272　(11)　7259-7263　1997/03

    DOI： 10.1074/jbc.272.11.7259 　

    ISSN： 0021-9258

  114. Protein kinase C and c-myc gene activation pathways in thrombopoietin signal transduction Peer-reviewed

    M Kunitama, R Shimizu, M Yamada, T Kato, H Miyazaki, K Okada, Y Miura, N Komatsu

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　231　(2)　290-294　1997/02

    DOI： 10.1006/bbrc.1996.5969 　

    ISSN： 0006-291X

  115. Myelodysplastic syndrome. Elucidation of preleukemia condition. Pathophysiology of myelodysplastic syndrome. Centering round recent progress. Apoptosis.

    清水律子, 小松則夫

    モダンフィジシャン　17　(10)　1997

    ISSN： 0913-7963

  116. Hematopoietic System and Apoptosis. Inhibition of apoptosis through cytokine receptor.

    清水律子

    臨床免疫　29　(4)　1997

    ISSN： 0386-9695

  117. Thrombopoietin signal transduction via its receptor encoded by c-mpl: its association with hematological diseases.

    高徳正昭, 清水律子

    臨床血液　38　(3)　1997

    ISSN： 0485-1439

  118. Role of c-jun in the inhibition of erythropoietin receptor-mediated apoptosis Peer-reviewed

    R Shimizu, N Komatsu, Y Nakamura, H Nakauchi, Y Nakabeppu, Y Miura

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　222　(1)　1-6　1996/05

    DOI： 10.1006/bbrc.1996.0688 　

    ISSN： 0006-291X

  119. Role of c-jun in the Inhibition of Apoptosis through the Erythropoietin Receptor.

    清水律子, 小松則夫

    臨床血液　37　(7)　1996

    ISSN： 0485-1439

  120. [Retrospective analysis on 21 patients with follicular lymphoma]. Peer-reviewed

    Izumi T, Imagawa S, Muroi K, Shimizu R, Takahashi H, Hoshino Y, Tomizuka H, Kawakami T, Toya K, Kurata H, Tsunoda J, Furukawa Y, Suzuki T, Komatsu N, Ohsaka A, Amemiya Y, Takagi S, Yoshida M, Sasaki R, Hatake K, Miura Y

    Rinsho Ketsueki　37　(1)　7-13　1996/01

    Publisher:

    DOI： 10.11406/rinketsu.37.7 　

    ISSN： 0485-1439

  121. Hepatitis C virus infection in Waldenstrom's macroglobulinemia [6] Peer-reviewed

    T. Izumi, R. Sasaki, R. Shimizu, A. Miyazato, Y. Hoshino, Y. Miura, H. Okamoto

    American Journal of Hematology　52　(3)　238-239　1996

    DOI： 10.1002/(SICI)1096-8652(199607)52:3<238::AID-AJH25>3.0.CO;2-A 　

    ISSN： 0361-8609

  122. Combination chemotherapy of carboplatin and cytosine arabinoside for high-risk leukemia: A pilot study Peer-reviewed

    N Iwao, M Yoshida, K Hatake, Y Hoshino, S Hagiwara, H Tomizuka, R Shimizu, T Suzuki, Y Furukawa, N Komatsu, K Muroi, A Miwa, S Sakamoto, Y Miura

    LEUKEMIA RESEARCH　19　(12)　899-903　1995/12

    ISSN： 0145-2126

  123. ERYTHROPOIETIN INDUCES TYROSINE PHOSPHORYLATION AND ACTIVATION OF PHOSPHOLIPASE C-GAMMA-1 IN A HUMAN ERYTHROPOIETIN-DEPENDENT CELL-LINE Peer-reviewed

    HY REN, N KOMATSU, R SHIMIZU, K OKADA, Y MIURA

    JOURNAL OF BIOLOGICAL CHEMISTRY　269　(30)　19633-19638　1994/07

    ISSN： 0021-9258

  124. Special issue : MRSA infectious disease countermeasure and G-CSF 2.Treatment and countermeasure of hemopathy and MRSA.Clinical case.6.

    清水律子, 小松則夫, 室井一男, 畠清彦, 吉田稔, 坂本忍, 三浦恭定, 腰塚史朗, 金井信行

    日常診療と血液　3　(11)　1993

    ISSN： 0917-5776

Show all ︎Show first 5

Misc. 69

  1. 幹細胞から赤血球への通り道 GATA転写因子群と赤血球分化(GATA transcription factors and erythroid differentiation)

    山本 雅之, 清水 律子

    日本血液学会学術集会　83回　PSY-3　2021/09

    Publisher: (一社)日本血液学会

  2. GATA factor-related hematopoietic diseases

    清水律子

    臨床血液　61　(9)　2020

    ISSN： 0485-1439

  3. 急性巨核芽球性白血病に対するNOTCH活性化剤による新規治療(Notch activation impedes cell proliferation and survival in acute megakaryoblastic leukemia)

    大里 元美, Ong Kelly Ooi Kee, Mok Michelle Meng Huang, 横溝 智雅, 松村 貴由, 須田 年生, 麻生 範雄, Koeffler Phillip, Tenen Daniel G., 清水 律子, 山本 雅之, 伊藤 嘉明, Yeoh Allen Eng-Juh, Chng Wee Joo

    臨床血液　59　(9)　1700-1700　2018/09

    Publisher: (一社)日本血液学会-東京事務局

    ISSN： 0485-1439

    eISSN： 1882-0824

  4. ESTABLISHMENT OF IN VIVO AND IN VITRO MODEL OF X-LINKED SIDEROBLASTIC ANEMIA

    K. Saito, T. Fujiwara, M. Morita, Y. Okitsu, N. Fukuhara, Y. Onishi, Y. Nakamura, R. Shimizu, H. Harigae

    HAEMATOLOGICA　102　241-241　2017/06

    ISSN： 0390-6078

  5. 巨核球造血の転写制御機構 (特集 巨核球造血と血小板産生の新知見)

    平野 育生, 清水 律子

    血液フロンティア　27　(6)　821-826　2017/06

    Publisher: 医薬ジャーナル社

    ISSN： 1344-6940

  6. 赤血球造血におけるGATA1研究の新たな展開

    長谷川 敦史, 清水 律子

    血液内科　73　(2)　221-227　2016/08

    Publisher: (有)科学評論社

    ISSN： 2185-582X

  7. GATA1 Changes DNA-Binding Fashion in a Binding-Site-Specific Manner and Alters Transcriptional Activity during Erythropoiesis

    Atsushi Hasegawa, Hiroshi Kaneko, Daishi Ishihara, Masahiro Nakamura, Akira Watanabe, Cecelia D. Trainor, Yamamoto Masayuki, Ritsuko Shimizu

    BLOOD　126　(23)　2015/12

    ISSN： 0006-4971

    eISSN： 1528-0020

  8. GATA-2 Regulates Dendritic Cell Differentiation

    Koichi Onodera, Tohru Fujiwara, Yasushi Onishi, Ari Itoh-Nakadai, Yoko Okitsu, Noriko Fukuhara, Kenichi Ishizawa, Ritsuko Shimizu, Masayuki Yamamoto, Hideo Harigae

    BLOOD　126　(23)　2015/12

    ISSN： 0006-4971

    eISSN： 1528-0020

  9. エリスロポエチン遺伝子の腎特異的転写制御領域の解析と腎性貧血モデルマウスの樹立

    平野育生, 鈴木教郎, 祢津昌広, 関根弘樹, 相馬友和, 峯岸直子, 清水律子, 山本雅之

    日本生化学会大会(Web)　88回・38回　[4T5L-10(3P0698)]　2015/12

    Publisher: (公社)日本生化学会

  10. 動き出した創薬オープンイノベーションネットワーク アカデミック創薬 東北からの発信

    青木 淳賢, 可野 邦行, 濱 直人, 辻田 忠志, 土井 隆行, 菅原 明, 清水 律子, 大島 吉輝, 山本 雅之

    日本薬学会年会要旨集　135年会　(1)　155-155　2015/03

    Publisher: (公社)日本薬学会

    ISSN： 0918-9823

  11. Generation of Nrf2 point mutant mice by CRISPR/Cas9 system

    Masanobu Morita, Takafumi Suzuki, Hiromi Suda, Akihito Otsuki, Mikiko Suzuki, Ritsuko Shimizu, Masayuki Yamamoto

    TRANSGENIC RESEARCH　23　(5)　874-874　2014/10

    ISSN： 0962-8819

    eISSN： 1573-9368

  12. GATA2 REGULATES DIFFERENTIATION OF BONE MARROW-DERIVED MESENCHYMAL STEM CELLS

    M. Kamata, Y. Okitsu, T. Fujiwara, S. Nakajima, T. Takahashi, A. Inoue, N. Fukuhara, Y. Onishi, K. Ishizawa, R. Shimizu, M. Yamamoto, H. Harigae

    HAEMATOLOGICA　99　173-173　2014/06

    ISSN： 0390-6078

  13. 【赤血球造血の基礎と臨床】 赤血球分化の決定機構

    清水 律子

    血液フロンティア　24　(4)　559-564　2014/03

    Publisher: (株)医薬ジャーナル社

    ISSN： 1344-6940

  14. トランスジェニックマウスを利用したエリスロポエチン遺伝子エンハンサーの探索

    平野育生, 鈴木教郎, 山崎瞬, 峯岸直子, 山本雅之, 清水律子

    日本分子生物学会年会プログラム・要旨集(Web)　36th　1P-0195 (WEB ONLY)　2013

  15. DNA Binding Diversity Achieved Through the Interaction of GATA1 N-Finger and GATA Motif Is Important for Embryonic Erythropoiesis

    Atsushi Hasegawa, Ritsuko Shimizu, Hirofumi Kurokawa, Masayuki Yamamoto

    BLOOD　120　(21)　2012/11

    ISSN： 0006-4971

  16. GATA1 Mutants Lacking Rb-Binding Motif Observed in Transient Abnormal Myelopoiesis in Down Syndrome

    Tsutomu Toki, Eri Kobayashi, Rika Kanezaki, RuNan Wang, Kiminori Terui, Hirokazu Kanegane, Miho Maeda, Mikiya Endo, Tatsuki Mizuochi, Souichi Adachi, Yasuhide Hayashi, Ritsuko Shimizu, Masayuki Yamamoto, Etsuro Ito

    BLOOD　118　(21)　647-647　2011/11

    ISSN： 0006-4971

  17. Two Distinct Transactivation Domains of GATA1 Contribute Megakaryopoiesis

    Hiroshi Kaneko, Eri Kobayashi, Ritsuko Shimizu, Masayuki Yamamoto

    BLOOD　118　(21)　1451-1451　2011/11

    ISSN： 0006-4971

  18. 白血病の発症機構とその要因 遺伝、発生/発達の視点から GATA1転写因子の機能異常と白血病 (臨床血液) Invited

    清水律子

    臨床血液　52　(8)　695-702　2011/08

    Publisher: The Japanese Society of Hematology

    DOI： 10.11406/rinketsu.52.695 　

    ISSN： 0485-1439

  19. 転写因子GATA1の機能破綻に起因する急性巨核芽球性白血病発症メカニズムの解析

    清水 律子

    癌と人　38　(38)　40-41　2011/05

    Publisher: (公財)大阪癌研究会

  20. Leukemogenesis caused by dysfunctions of GATA1 transcription factor

    清水律子

    臨床血液　52　(8)　2011

    ISSN： 0485-1439

  21. GATA1関連白血病 (東北医学雑誌)

    清水律子

    東北医学雑誌　121　(2)　165-168　2009/12

    Publisher: 東北医学会

    ISSN： 0040-8700

  22. Spherocytic Hemolytic Anemia Caused by Disruption of GATA1-FOG1 Interaction

    Ritsuko Shimizu, Atsushi Hasegawa, Masayuki Yamamoto

    BLOOD　114　(22)　321-321　2009/11

    ISSN： 0006-4971

  23. Compound Deficiency of Nrf2 and Selenoproteins in Hematopoietic Cells Leads to Severe Defects in Erythroid and Lympboid Lineage Development

    Yukie Kawatani, Takafumi Suzuki, Ritsuko Shimizu, Vincent Kelly, Masayuki Yamamoto

    BLOOD　114　(22)　788-788　2009/11

    ISSN： 0006-4971

  24. 相補レスキュー法を用いたGATA1転写因子の機能解析 (東北大学医学部保健学科紀要)

    清水律子

    東北大学医学部保健学科紀要　18　(2)　75-81　2009/07

    Publisher: 東北大学医学部保健学科

    ISSN： 1348-8899

  25. 相補レスキュー法を用いたGATA1転写因子の機能解析

    清水律子

    東北大学医学部保健学科紀要　18　(2)　2009

    ISSN： 1348-8899

  26. Induction of Hyperproliferative Fetal Megakaryopoiesis by An N-Terminally Truncated GATA1 Mutant

    Ritsuko Shimizu, Eri Kobayashi, James Engel, Masayuki Yamamoto

    BLOOD　112　(11)　434-435　2008/11

    ISSN： 0006-4971

  27. GATA-1の機能異常と白血病 (日本産婦人科・新生児血液学会誌)

    安部加奈子, 清水律子, 山本雅之

    日本産婦人科・新生児血液学会誌　17　(2)　1-8　2008/03

    ISSN： 0916-8796

  28. Leukemia-related transcription factor TEL expands erythroid precursors Peer-reviewed

    Kinuko Mitani, Minenori Eguchi-Ishimae, Kazuhiro Maki, Ritsuko Shimizu, Masayuki Yamamoto, Mariko Eguchi

    BLOOD　110　(11)　108B-108B　2007/11

    ISSN： 0006-4971

  29. GATA因子スイッチングとGATA-1関連白血病

    清水 律子, 山本 雅之

    生化学　79　(10)　941-952　2007/10

    Publisher: (公社)日本生化学会

    ISSN： 0037-1017

  30. マウスGATA-1関連白血病と白血病幹細胞の遺伝学的解析 (日本癌学会総会記事)

    山本雅之, 安部加奈子, 清水律子

    日本癌学会総会記事　66回　248-248　2007/08

  31. SREBP-1c遺伝子のin vivoプロモーター解析

    武内 謙憲, 矢作 直也, 中川 嘉, 関谷 元博, 松坂 賢, 大橋 健, 位高 啓史, 片岡 一則, 山崎 力, 永井 良三, 清水 律子, 山本 雅之, 山田 信博, 大須賀 淳一, 門脇 孝, 島野 仁

    糖尿病　50　(Suppl.1)　S-278　2007/04

    Publisher: (一社)日本糖尿病学会

    ISSN： 0021-437X

  32. Dynamic regulation of gata factor levels is more important than their identity

    Rita Ferreira, Albert Wai, Ritsuko Shimizu, Nynke Gillemans, Robbert Rottier, Marieke von Lindern, Kinuko Ohneda, Frank Grosveld, Masayuki Yamamoto, Sjaak Philipsen

    BLOOD CELLS MOLECULES AND DISEASES　38　(2)　171-172　2007/03

    DOI： 10.1016/j.bcmd.2006.10.117 　

    ISSN： 1079-9796

  33. TAL-1 and GATA-1 coupled cell proliferation and differentiation during terminal erythroid differentiation

    Zahra Kadri, Nicolas Goardon, Ritsuko Shimizu, Osamu Ohneda, Tran Hoang, Philippe Leboulch, Sylvie Gisselbrecht, Masayuki Yamamoto, Stany Chretien, Paul Henri Romeo

    BLOOD CELLS MOLECULES AND DISEASES　38　(2)　175-176　2007/03

    DOI： 10.1016/j.bcmd.2006.10.125 　

    ISSN： 1079-9796

  34. Developmental regulation of Gata1 gene expression through adjacent GATA boxes and CP2-binding sites

    Ritsuko Shimizu, Rie Fujita, Shinya Ohmori, Sergio Ottolenghi, Antonella Ronchi, Masayuki Yamamoto

    BLOOD CELLS MOLECULES AND DISEASES　38　(2)　177-177　2007/03

    DOI： 10.1016/j.bcmd.2006.10.128 　

    ISSN： 1079-9796

  35. Regulation of mouse Gatal gene expression in erythroid progenitors

    Masayuki Yamamoto, Mikiko Suzuki, Norio Suzuki, Ritsuko Shimizu

    BLOOD CELLS MOLECULES AND DISEASES　38　(2)　188-188　2007/03

    DOI： 10.1016/j.bcmd.2006.10.153 　

    ISSN： 1079-9796

  36. 赤血球造血におけるSUMO化GATA-1の生理的意義

    清水律子, 大森慎也, 森口尚, 山本雅之, 山本雅之

    生化学　2007

    ISSN： 0037-1017

  37. 【白血病の分子病態 最近の進歩】 GATA-1の機能異常と白血病 発現低下と構造異常 (血液・腫瘍科)

    安部加奈子, 清水律子

    血液・腫瘍科　52　(6)　625-630　2006/06

  38. The direct association of GATA-1 to rb is necessary for definitive erythropoiesis.

    Z Kadri, R Shimizu, S Gisselbrecht, O Ohneda, M Yamamoto, PH Romeo, S Chretien

    BLOOD　106　(11)　94A-94A　2005/11

    ISSN： 0006-4971

  39. ユビキチン・プロテアソーム経路を介したGATA-2の迅速な代謝回転 (日本血液学会・日本臨床血液学会総会プログラム・抄録集)

    峯岸直子, 鈴木教郎, 川谷幸恵, 清水律子, 山本雅之

    日本血液学会・日本臨床血液学会総会プログラム・抄録集　67回・47回　749-749　2005/09

    Publisher: 日本臨床血液学会

  40. 【血液疾患 state of arts】 病態生理に関する基礎的・臨床的研究 最近の進歩 病態研究 血液疾患に対する発生工学的アプローチ 転写因子GATA-1の機能破綻と血液疾患 (医学のあゆみ)

    清水律子, 山本雅之

    医学のあゆみ　別冊　(血液疾患-state of arts Ver.3)　187-190　2005/09

  41. Application of Modern Biotechnology and Mouse Genetics for the Study of Hematopoiesis Invited

    Yamamoto M, Shimizu R

    Education Program Book　157-163　2005/04

    Publisher: he Joint Meeting of the 67th Annual Meeting of Japanese Society of Hematology and the 47th Annual Meeting of Japanese Society of Clinical Hematology

  42. Self-association of GATA-1 is required for erythropoiesis in vivo.

    R Shimizu, K Ohneda, K Nishikawa, CD Trainor, M Yamamoto

    BLOOD CELLS MOLECULES AND DISEASES　34　(2)　122-122　2005/03

    ISSN： 1079-9796

  43. 病態生理に関する基礎的・臨床的研究:最近の進歩 47 病態研究 血液疾患に対する発生工学的アプローチ-転写因子GATA-1の機能破綻と血液疾患

    清水律子, 山本雅之

    医学のあゆみ　2005

    ISSN： 0039-2359

  44. 【転写制御と疾患 温故知新】 GATA-1変異と白血病 転写因子の質的異常と量的異常 (医学のあゆみ)

    長野真澄, 清水律子, 山本雅之

    医学のあゆみ　211　(2)　159-162　2004/10

  45. モデルマウスが教える造血制御と白血病発症 GATA-1ノックダウンマウス (Mebio)

    清水律子, 山本雅之

    Mebio　21　(8)　58-62　2004/08

  46. 転写制御と疾患-温故知新 GATA-1変異と白血病-転写因子の質的異常と量的異常

    長野真澄, 清水律子, 山本雅之

    医学のあゆみ　211　(2)　2004

    ISSN： 0039-2359

  47. A minigene containing four discrete cis elements recapitulates GATA-1 gene expression in vivo.

    K Ohneda, R Shimizu, S Takahashi, JD Enge, M Yamamoto

    BLOOD CELLS MOLECULES AND DISEASES　31　(1)　157-157　2003/07

    ISSN： 1079-9796

  48. MDSモデルマウス (分子細胞治療)

    清水律子

    分子細胞治療　2　(6)　628-632　2001/12

  49. 遺伝子改変マウスを用いた血液疾患病態の解明 (臨床血液)

    山本雅之, 清水律子

    臨床血液　42　(4)　233-236　2001/04

    Publisher: 日本臨床血液学会

    DOI： 10.11406/rinketsu.42.233 　

    ISSN： 0485-1439

  50. Functional role of STAT3 in vivo megakaryopoiesis.

    K Kirito, M Osawa, R Shimizu, A Oda, K Nakajima, H Morita, M Yamamoto, K Ozawa, N Komatsu

    BLOOD　96　(11)　538A-538A　2000/11

    ISSN： 0006-4971

  51. Regulation of mouse GATA-1 and GATA-2 genes.

    M Yamamoto, N Minegishi, R Shimizu, N Suzuki, S Takahashi

    BLOOD CELLS MOLECULES AND DISEASES　26　(5)　507-507　2000/10

    ISSN： 1079-9796

  52. GATA factor transgenes under GATA-1 locus control rescue germ line GATA-1 mutant deficiencies.

    R Shimizu, S Takahashi, JD Engel, M Yamamoto

    BLOOD CELLS MOLECULES AND DISEASES　26　(5)　527-528　2000/10

    ISSN： 1079-9796

  53. 赤血球・巨核球造血におけるStat3の役割 トランスジェニックマウスを用いた機能解析

    桐戸敬太, 田中勝, 大沢匡毅, 森田晴彦, 清水律子, 山本雅之, 小沢敬也, 小松則夫

    International Journal of Hematology. Supplement　71　(1)　179　2000/04

    ISSN： 0917-1258

  54. 医学と医療の最前線 血液細胞と転写因子 (日本内科学会雑誌) Invited

    清水律子, 山本雅之

    日本内科学会雑誌　88　(10)　2057-2063　1999/10

    Publisher: The Japanese Society of Internal Medicine

    DOI： 10.2169/naika.88.2057 　

    ISSN： 0021-5384

  55. Blood cell and transcription factor.

    清水律子, 山本雅之

    日本内科学会雑誌　88　(10)　1999

    ISSN： 0021-5384

  56. Stat3 has a negative effect on the thrombopoietin-induced megakaryocytic differentiation of a human leukemia cell line.

    K Kirito, M Tanaka, R Shimizu, M Uchida, M Takatoku, K Nakajima, T Hirano, A Takeshita, Y Miura, K Ozawa, N Komatsu

    BLOOD　92　(10)　63A-63A　1998/11

    ISSN： 0006-4971

  57. 【貧血 診療に必須の最新情報】 ベーシックな知識を蓄える 造血の鍵をにぎる転写因子 研究の最前線 (内科) Invited

    清水律子, 山本雅之

    内科　82　(3)　417-421　1998/09

  58. Role of mitogen-activated protein kinase in the cell differentiation into erythroid and megakaryocytic lineages.

    M Uchida, K Kirito, R Shimizu, Y Miura, K Ozawa, N Komatsu

    EXPERIMENTAL HEMATOLOGY　26　(8)　685-685　1998/08

    ISSN： 0301-472X

  59. Anemia. Essential latest information for medical care. Reserving basic knowledge.Transcription factor holding key of hemopoiesis. Forefront of research.

    清水律子, 山本雅之

    内科　82　(3)　1998

    ISSN： 0022-1961

  60. A dominant negative effect of a truncated erythropoietin receptor on erythropoietin-induced erythroid differentiation.

    R Shimizu, N Komatsu, Y Miura

    BLOOD　90　(10)　240-240　1997/11

    ISSN： 0006-4971

  61. 【骨髄異形成症候群-前白血病状態を解き明かす】 骨髄異形成症候群の病態生理 最近の進歩を中心に アポトーシス (Modern Physician)

    清水律子, 小松則夫

    Modern Physician　17　(10)　1189-1192　1997/10

  62. 造血系とアポトーシス サイトカインレセプターとアポトーシス (臨床免疫) Invited

    清水律子

    臨床免疫　29　(4)　448-453　1997/04

  63. サイトカインレセプターの性状とその異常 トロンボポエチン受容体を介した細胞内シグナル伝達とその異常 (臨床血液)

    高徳正昭, 清水律子

    臨床血液　38　(3)　203-208　1997/03

    DOI： 10.11406/rinketsu.38.203 　

  64. Thrombopoietin has a direct effect on erythroid differentiation

    M Yamada, N Komatsu, K Kirito, R Shimizu, T Kato, H Miyazaki, K Abe, Y Miura

    EXPERIMENTAL HEMATOLOGY　24　(9)　456-456　1996/08

    ISSN： 0301-472X

  65. Analysis of functional domains of the human TPO receptor encoded by c-Mpl

    M Takatoku, N Komatsu, R Shimizu, T Kato, H Miyazaki, Y Miura

    EXPERIMENTAL HEMATOLOGY　24　(9)　457-457　1996/08

    ISSN： 0301-472X

  66. 血液疾患におけるアポトーシス サイトカインレセプターとアポトーシス (臨床血液)

    清水律子, 小松則夫

    臨床血液　37　(7)　526-530　1996/07

    Publisher: The Japanese Society of Hematology

    DOI： 10.11406/rinketsu.37.526 　

    ISSN： 0485-1439

  67. ROLE OF C-JUN IN THE INHIBITION OF APOPTOSIS THROUGH THE ERYTHROPOIETIN RECEPTOR

    R SHIMIZU, N KOMATSU, Y NAKAMURA, H NAKAUCHI, Y NAKABEPPU, Y MIURA

    EXPERIMENTAL HEMATOLOGY　23　(8)　831-831　1995/08

    ISSN： 0301-472X

  68. Analysis of erythropoietin acceptor structure and oncogene expression concerning apoptosis. ( Ministry of Health and Welfare S )

    三浦恭定, 清水律子, 小松則夫, 中村幸夫, 中内啓光

    特発性造血障害調査研究班 平成6年度研究業績報告書　168-169　1995

  69. 急性骨髄性白血病完全寛解期に発症したメチシリン・セフェム耐性黄色ブドウ球菌(MRSA)腸炎の1例 Peer-reviewed

    清水律子

    34　(10)　1373-1373　1993/10

Show all ︎Show first 5

Books and Other Publications 1

  1. 未来型血液治療学

    小松, 則夫

    中外医学社　2019/10

    ISBN: 9784498225183

Presentations 52

  1. Loss of the Gata1 Gene IE Exon Leads to Variant Transcript Expression and the Production of a GATA1 Protein Lacking the N-terminal Domain.

    Kobayashi E, Shimizu R, Kikuchi Y, Takahashi S, Yamamoto M

    2010/12/07

  2. GATA2 in Urogenital development. Invited

    Moriguchi T, Ainoya K, Ohmori S, Morita M, Chandler KJ, Mortlock DP, Shimizu R, Lim K-C, Engel JD, Yamamoto M

    2010/11/17

  3. Regulation of Gata1 gene in vivo with the cis-acting functional motifs and GATA factor switching Invited

    Takai J, Moriguchi T, Suzuki M, Ohneda K, Shimizu R, Yamamoto M

    2010/11/18

  4. Hasegawa A, Shimizu R, Yamamoto M. International-presentation

    Spehrocytic hemolytic, anemia cased, y disruption of GATA, FOG, interaction

    International Symposium on GATA Factors　2010/11/17

  5. Roles of GATA1/Rb interaction in control of megakaryocyte proliferation. International-presentation

    Kobayashi E, Shimizu R, Toki T, Ito E, Yamamoto M

    International Symposium on GATA factors　2010/11/17

  6. Identification and analysis of novel transactivation domain of transcription factor GATA1. International-presentation

    Hiroshi K, Kawatani Y, Shimizu R, Yamamoto M

    International Symposium on GATA factors　2010/11/17

  7. Regulation of Gata1 gene in vivo with the cis-acting functional motifs and GATA factor switching. International-presentation

    Takai J, Moriguchi T, Suzuki M, Ohneda K, Shimizu R, Yamamoto M

    International Symposium on GATA factors　2010/11/17

  8. Multi-step leukemogenesis caused by N-terminally truncated GATA1 mutants. International-presentation

    Shimizu R, Kobayashi E, Engel, JD, Yamamoto M

    International Symposium on GATA factors　2010/11/17

  9. Spherocytic hemolytic anemia causedby disruption of GATA1-FOG1 interaction International-presentation

    Shimizu R, Hasegawa A, Yamamoto M

    Conference on Hemoglobin Switching　2010/09/01

  10. SUMO-conjugated GATA1 and GATA Factor Switching. International-presentation

    Shimizu R, Ohmori S, Hasegawa A, Kaneko H, Moriguchi T, Yamamoto M

    Conference on Hemoglobin Switching　2010/09/01

  11. Hemolytic Anemia Caused by Disruption of GATA1-FOG1 Interaction. International-presentation

    Hasegawa A, Shimizu R, Yamamoto M

    Interaction. JSH International Symposium　2010/07/16

  12. Compound Deficiency of Nrf2 and Selenoproteins in Hematopoietic Cells Leads to Severe Defects in Erythroid and Lymphoid Lineage Development. International-presentation

    Kawatani Y, Suzuki T, Shimizu R, Kelly VP, Yamamoto M

    International Symposium on Selenium in Biology and Medicine. Kyoto, May.31-June 4, 2010 (Abstract p38)　2010/05/31

  13. Loss of the Gata1 Gene IE Exon Leads to Variant Transcript Expression and the Production of a GATA1 Protein Lacking the N-terminal Domain.

    Kobayashi E, Shimizu R, Kikuchi Y, Takahashi S, Yamamoto M

    2009/12/07

  14. Spherocytic hemolytic anemia caused by disruption of GATA1-FOG1 interaction.

    Shimizu R, Hasegawa A, Yamamoto M

    2009/12/07

  15. Acquired loss of IE exon of Gata1 gene causes expression of variant transcripts and leads to production of N-terminus truncated GATA1 protein. International-presentation

    Shimizu R, Kobayashi EEngel JD, Yamamoto M

    Red Cell Gordon Conference　2009/06/28

  16. GATA factor switching during erythroid differentiation International-presentation

    Yamamoto M, Moriguchi, T, Suzuki, M, Shimizu R

    Red cell Gordon Conference　2009/06/28

  17. Compound Deficiency of Nrf2 and Selenoproteins in Hematopoietic Cells Leads to Severe Defects in Erythroid and Lymphoid Development

    2009/12/07

  18. Induction of Hyperproliferative Fetal Megakaryopoiesis by an N-terminally Truncated GATA1 Mutant International-presentation

    Shimizu R, Engel JD, Yamamoto M

    ASH Annual Meeting　2008/12/06

  19. Gata1 Gene Regulation and GATA1-related Leukemia International-presentation

    Yamamoto M, Moriguchi, T, Suzuki, M, Shimizu R

    Conference on Hemoglobin Switching　2008/10/11

  20. Induction of Hyperproliferative Fetal Megakaryopoiesis by an N-terminally Truncated GATA1 Mutant International-presentation

    Shimizu R, Engel JD, Yamamoto M

    Conference on Hemoglobin Switching　2008/10/11

  21. GATA-2 in Auditory and Neuronal System International-presentation

    Tomofumi Hoshino, Ritsuko Shimizu, Masayuki Yamamoto, Akira Hara

    Midwinter Research Meeting of Association for Research in Otolaryngology　2008/02/16

  22. Leukemia-related transcription factor TEL expands erythroid precursors International-presentation

    Minenori Eguchi-Ishimae, Mariko Eguchi, Kazuhiro Maki, Ritsuko Shimizu, Masayuki Yamamoto M, Kinuko Mitani

    Annual meeting of American Society of Hematology　2007/12/08

  23. Stem cells in GATA-1 knockdown leukemia are held in quiescence and released into cell cycle after 5-fluorouracil treatment. The 11th Germany-Japan Cancer Workshop, Kyoto, Japan, Nov. 29-Dec. 1, 200 Invited

    Shimizu R, Abe K, Yamamoto M

    2007/11/30

  24. Stem cells in GATA-1 knockdown leukemia are held in quiescence and released into cell cycle after 5-fluorouracil treatment

    Shimizu R, Abe K, Yamamoto M

    Germany-Japan Cancer Workshop　2007/11/29

  25. Increase of hematopoietic progenitors but impairment of erythroid and megakaryocytic differentiation in transgenic mice expressing SET-CAN International-presentation

    Syoko Saito, Kaoru Nouno, Ritsuko Shimizu, Masayuki Yamamoto, Kyosuke Nagata

    Stem cell Gordon Conference　2007/09/09

  26. Analyses of leukemic stem cells of GATA-1 related leukemia International-presentation

    Kanako Abe, Ritsuko Shimizu, Xiaoqing Pan, Hiromi Hamada, Hiroyuki Yoshikawa, Masayuki Yamamoto

    Stem cell Gordon Conference　2007/09/09

  27. Transcription Factor GATA-2 Regulates Self-renewal of Hematopoietic Stem Cells International-presentation

    Ritsuko Shimizu, Tomofumi Hoshino, Norio Suzuki, Masayuki Yamamoto

    Stem cell Gordon Conference　2007/09/09

  28. Sumo-modification of GATA-1 at lysine-137 is important for erythropoiesis through its ability to repress Gata2 transcription International-presentation

    Shimizu R, Ohmori S, Engel JD, Yamamoto M

    International Symposium on GATA Factors　2007/04/14

  29. Construction of transgenic mice expressing novel beetle luciferase International-presentation

    Tomoko Michihata, Tamotsu Noguchi, Yoshihiro Nakajima, Ritsuko Shimizu, Masayuki Yamamoto, Yoshihiro Ohmiya

    nternational Symposium on Bioluminescence and Chemiluminescence　2006/10/15

  30. Dynamic regulation of gata factor levels is more important than their identity International-presentation

    Rita Ferreira, Albert Wai, Ritsuko Shimizu, Nynke Gillmans, Robbert Rottier, Marieke von Lindern, Kinuko Ohneda, Frank Grosveld, Masayuki Yamamoto, Sjaak Philipsen

    Hemoglobin Switching Conference　2006/09/15

  31. TAL-1 and GATA-1 coupled cell proliferation and differentiation during terminal erythroid differentiation International-presentation

    Zahra Kadri, Nicolas Goardon, Ritsuko Shimizu, Osamu Ohneda O, Tran Hoang, Philippe Leboulch, Sylveie Gisselbrecht, Masayuki Yamamoto, Stany Chretien, Paul-Henri Romeo

    Hemoglobin Switching Conference　2006/09/15

  32. Regulation of Mouse Gata1 Gene Expression in Erythroid Progenitors International-presentation

    Masayuki Yamamoto, Mikiko Suzuk, Norio Suzuki, Ritsuko Shimizu

    Hemoglobin Switching Conference　2006/09/15

  33. Developmental regulation ofGata1 gene expression through adjacent GATA boxes and CP2-binding sites International-presentation

    Ritsuko Shimizu, Rie Fujita, Shinya Ohmori, Sergio Ottolenghi, Antonella Ronchi, Masayuki Yamamoto

    Hemoglobin Switching Meeting　2006/09/14

  34. The direct association of GATA-1 to rb is necessary for definitive erythropoiesis International-presentation

    Zahra Kadri, Ritsuko Shimizu, Sylveie Gisselbrecht, Osamu Ohneda, Masayuki Yamamoto, Paul-Henri Romeo, Stany Chretien

    American Society of Hematology　2005/12/08

  35. Gene expression regulation and domain function of hematopoietic GATA factors

    Masayuki Yamamoto, Ritsuko Shimizu, Kinuko Ohneda, Norio Suzuki

    apanese Biochemical Society Meeting　2005/10/19

  36. Establishment of GATA-1-deficient GAK14 Cells and Examination of Roles N-terminal Domain of GATA-1 Play during Erythroid Differentiation International-presentation

    Harumi Y. Mukai, Masumi Nagano, Osamu Ohneda, Kinuko Ohneda, Ritsuko Shimizu, Masayuki Yamamoto

    Red cell Gordon Conference　2005/06/11

  37. Contribution of NT Domain of GATA-1 and Runx1 to the Definitive Erythropoiesis. International-presentation

    Ritsuko Shimizu, Kinuko Ohneda, Masayuki Yamamoto

    Red cell Gordon Conference　2005/06/11

  38. Rescue of GATA1 null Mice by GATA Transgenes Requires the Correct Spatio-Temporal Expression Pattern International-presentation

    Rita Ferreira, Albert Wai, Ritsuko Shimizu, Nynke Gillmans, Robbert Rottier, Marieke von Lindern, Kinuko Ohneda, Masayuki Yamamoto, Frank Grosveld, Sjaak Philipsen

    Hemoglobin Switching Meeting　2004/09/10

  39. A New Pathway for Definitive Hematopoiesis Revealed in the Transgenic Rescue of Runx1-deficient Mouse International-presentation

    Tomomasa Yokomizo, Satoru Takahashi, Naoko Mochizuki, Takashi Kuroha, Masatsugu Ema, Ritsuko Shimizu, Osamu Ohneda, Motomi Osato, Hitoshi Okada, Minetaro Ogawa, Shin-Ichi Nishikawa, Yoshiaki Ito, Masayuki Yamamoto

    Hemoglobin Switching Meeting　2004/09/10

  40. Self-Associationof GATA-1 is Required for Erythropoiesis In Vivo International-presentation

    Ritsuko Shimizu, Kinuko Ohneda, Keizo Nishikawa, Cecelia D. Trainor, Masayuki Yamamoto

    Hemoglobin Switching Meeting　2004/09/10

  41. Transgenic rescue of runx1-deficient mice reveals the heterogeneity of he definitive hematopoietic pathway International-presentation

    Satoru Takahashi, Tomomasa Yokomizo, Naoko Mochizuki, Takashi Kuroha, Ritsuko Shimizu, Osamu Ohneda, Motomi Osato, Hitoshi Okada, Minetaro Ogawa, Shin-Ichi Nishikawa, Yoshiaki Ito, Masayuki Yamamoto

    3rd International Symposium on GATA Factors　2003/07/17

  42. GATA-2 and hematopoietic stem cells International-presentation

    Norio Suzuki, Osamu Ohneda, Naoko Minegishi, Maki Osaki, Masumi Nagano, Ritsuko Shimizu, James Douglas Engel, Masayuki Yamamoto

    International Symposium on GATA Factors　2003/07/17

  43. Leukemogenesis caused by incapacitated GATA-1 function. The 3rd International Symposium on GATA Factors International-presentation

    Ritsuko Shimizu, Osamu Ohneda, Takashi Kuroha, Satoru Takahashi, Sjaak Philipsen, James Douglas Engel, Masayuki Yamamoto

    International Symposium on GATA Factors　2003/07/15

  44. A minigene containing four discrete cis elements recapitulates GATA-1 gene expression in vivo

    Kinuko Ohneda, Ritsuko Shimizu, Satoru Takahashi, James Douglas Engel, Masayuki Yamamoto

    2002/09/26

  45. Functional role of Stat3 in megakaryopoiesis: in vivo.

    2000/12/08

  46. Regulation of the murine GATA-2 and GATA-3 gene. Invited

    James Douglas Engel, Melin Khandekar, Ganesh Lakshmanan, Ken H. Lieuw K, Qinghui Liu, Kim-Chew Lim, Naoko Minegishi, Ritsuko Shimizu, Naruyoshi Suwabe, Satoru Takahashi, Masayuki Yamamoto, Yinghui Zhou

    The 2nd International Symposium on GATA Factors　2000/11/18

  47. Functional GATA-1 domain analysis with transgenic rescue of germ line GATA-1 mutant mouse.

    2000/11/18

  48. Regulation and domain function analyses of GATA-1 and GATA-2 Invited

    Masayuki Yamamoto, Naoko Minegishi, Ritsuko Shimizu, Norio Suzuki, Xiaoqing Pan, Maki Osaki, James Douglas Engel

    The 2nd International Symposium on GATA factors “GATA Factor Functions in Development”　2000/11/19

  49. Functional GATA-1 domain analysis with transgenic rescue of germ line GATA-1 mutant deficiencies.

    2000/06/09

  50. Regulation of Mouse GATA-1 and GATA-2 Gene Invited

    Shimizu R, Yamamoto M

    The 12th Conference on Hemoglobin Switching　2000/06/11

  51. Dominant negative effect of a truncated erythropoietin receptor on erythropoietin-induced erythroid differentiation.

    Ritsuko Shimizu, Norio Komatsu, Yasusada Miura

    1997/12/06

  52. Role of c-Jun in the inhibition of apoptosis through the erythropoietin receptor.

    Ritsuko Shimizu, Norio Komatsu, Yukio Nakamura, Hiromitsu Nakauchi, Yusaku Nakabeppu, Yasusada Miura

    1995/08/29

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Research Projects 2

  1. ドライバー変異と協調して白血病発症を修飾する遺伝的素因の探索

    清水 律子, 平野 育生, 長谷川 敦史

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(B)

    Institution: 東北大学

    2019/04/01 - 2023/03/31

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    ヒト純赤白血病は比較的稀な白血病であり、その発症メカニズムの詳細は分かっていない。我々は、赤血球造血に必須な転写因子GATA1の機能異常が純赤白血病発症に関与している可能性を考えている。GATA1遺伝子はX染色体上に存在するため、GATA1遺伝子に変異をヘテロに持つマウスは変異アリルが活性化した細胞と野生型アリルが活性化した細胞が共存する。GATA1ノックダウンアリルを持つヘテロ雌は、GATA1ノックダウンアリルが活性化した細胞由来の細胞がドライバー遺伝子変異を獲得してcKit陽性CD71陽性の純赤白血病を発症すること、ノックアウトではアポトーシス死してしまう赤芽球前駆細胞が、ノックダウンでは僅かに存在するGATA1により分化できないまま残存するため、蓄積した赤芽球にドライバー変異が蓄積するためだと考えられる。本年度は、GATA1ノックダウンによる赤芽球系への影響を、マウス成獣を用いて解析した。ノックダウン雄マウスではGATA1機能不全による赤血球造血不全で胎生11.5日程度で死亡するため、また、ノックダウン雌マウスではX染色体のランダムな不活化により混在している正常赤芽球とGATA1ノックダウンにより分化異常を有する赤芽球を分離できないため、成獣でのGATA1の機能解析は困難であった。そこで、Hprt遺伝子座にGFPを挿入したレポーターマウスとのコンパウンドマウス（Gata1遺伝子発現が正常な細胞はGFP陽性となる）を樹立し、MEP（megakaryocyte erythroid progenitor）分画でのRNAseq解析と、ｃkit陽性のプロジェニター分画でのsingle cell RNAseq解析を行った。その結果、GATA1ノックダウンがあってもMEP分画までは分化しうるが、MEP分画の細胞は巨核球系の性質に偏っているというプレリミナリーな結果を得た。

  2. 血球分化の分子機構と臨床的解析 Competitive

    小松 則夫

    Offer Organization: 日本学術振興会

    System: 基盤研究B

    1997/04 - 2000/03

Teaching Experience 3

  1. 輸血学　筑波大学、東北大学

  2. 医化学　筑波大学、東北大学

  3. 血液学　東北大学

Other 7

  1. ダウン症に合併するTAMをモデルとしたがんの発症と退縮に関わるエピジェネティクスの解析

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    ダウン症に合併するTAMをモデルとしたがんの発症と退縮に関わるエピジェネティクスの解析

  2. GATA2による血球の運命決定機構とその破綻による白血病発症メカニズムの解析

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    GATA2による血球の運命決定機構とその破綻による白血病発症メカニズムの解析

  3. 白血病幹細胞の分子機構の解明と分子治療標的の同定

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    白血病幹細胞の分子機構の解明と分子治療標的の同定

  4. 造血機構の恒常性破綻と巨核芽球性白血病発症メカニズムの解析

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    造血機構の恒常性破綻と巨核芽球性白血病発症メカニズムの解析

  5. 多段階白血病発症の分子メカニズムの個体解析

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    多段階白血病発症の分子メカニズムの個体解析

  6. 白血病幹細胞に対する治療標的分子の同定

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    白血病幹細胞に対する治療標的分子の同定

  7. 転写因子GATA1の機能破綻に起因する急性巨核芽球性白血病発症メカニズムの解析

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    転写因子GATA1の機能破綻に起因する急性巨核芽球性白血病発症メカニズムの解析

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