東北大学研究者紹介

研究者詳細

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顔写真

シミズ　リツコ

清水　律子

Ritsuko Shimizu

所属

大学院医学系研究科　保健学専攻　臨床検査医科学講座（分子血液学分野）

職名

教授

学位

博士（医学）（自治医科大学）

researchmap

https://researchmap.jp/7000022549

J-GLOBAL ID

201801009867552249

経歴 7

2009年4月～継続中

東北大学　教授
1999年4月～ 2009年3月

筑波大学　講師
2002年9月～ 2003年9月

ミシガン大学
1998年10月～ 1999年3月

筑波大学　リサーチアソシエイト
1992年6月～ 1998年9月

自治医科大学　助手
1990年5月～ 1992年5月

芳賀赤十字病院　医員
1988年4月～ 1990年4月

慶應義塾大学付属病院　研修医

︎全件表示 ︎最初の5件までを表示

学歴 1

慶應義塾大学　医学部

～ 1988年3月31日

研究分野 1

ライフサイエンス / 血液、腫瘍内科学 /

受賞 1

日本血液学会奨励賞

2001年4月20日　日本血液学会

論文 130

Gaze Patterns of Children with Communication Difficulties Associated with Core Symptoms of Autism Spectrum Disorder.

Mika Kobayashi, Tomoko Kobayashi, Taku Obara, Akira Narita, Akimitsu Miyake, Tomohisa Suzuki, Mami Ishikuro, Masatsugu Orui, Eiichi N Kodama, Ritsuko Shimizu, Yohei Hamanaka, Yoko Izumi, Atsushi Hozawa, Nobuo Fuse, Atsuo Kikuchi, Gen Tamiya, Shigeo Kure, Shinichi Kuriyama, Masayuki Yamamoto

The Tohoku journal of experimental medicine　2025年6月12日

DOI： 10.1620/tjem.2025.J074 　
Integration of Digital Phenotyping and Genomics for Dry Eye Disease: Protocol for a Prospective Cohort Study. 国際誌

Ken Nagino, Yasutsugu Akasaki, Nobuo Fuse, Soichi Ogishima, Atsushi Shimizu, Akira Uruno, Yoichi Sutoh, Yayoi Otsuka-Yamasaki, Fuji Nagami, Jun Seita, Tomohiro Nakamura, Satoshi Nagaie, Makiko Taira, Tomoko Kobayashi, Ritsuko Shimizu, Atsushi Hozawa, Shinichi Kuriyama, Atsuko Eguchi, Akie Midorikawa-Inomata, Masahiro Nakamura, Akira Murakami, Shintaro Nakao, Takenori Inomata

JMIR research protocols　14　e67862　2025年5月12日

DOI： 10.2196/67862 　

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BACKGROUND: Dry eye disease (DED) is a common ocular condition with diverse and heterogeneous symptoms. Current treatment standards of DED include the post facto management of associated symptoms through topical eye drops. However, there is a need for predictive, preventive, personalized, and participatory medicine. The DryEyeRhythm mobile health app enables real-time data collection on environmental, lifestyle, host, and digital factors in a patient's daily environment. Combining these data with genetic information from biobanks could enhance our understanding of individual variations and facilitate the development of personalized treatment strategies for DED. OBJECTIVE: This study aims to integrate digital data from the DryEyeRhythm smartphone app with the Tohoku Medical Megabank database to create a comprehensive database that elucidates the interplay between multifactorial factors and the onset and progression of DED. METHODS: This prospective observational cohort study will include 1200 participants for the discovery stage and 1000 participants for the replication stage, all of whom have data available in the Tohoku Medical Megabank database. Participants will be recruited from the Community Support Center of Sendai, Miyagi Prefecture, Japan. Participant enrollment for the discovery stage was conducted from August 1, 2021, to June 30, 2022, and the replication stage will be conducted from August 31, 2024, to March 31, 2026. Participants will provide demographic data, medical history, lifestyle information, DED symptoms, and maximum blink interval measurements at baseline and after 30 days using the DryEyeRhythm smartphone app. Upon scanning a registration code, each participant's cohort ID from the Tohoku Medical Megabank database will be linked to their smartphone app, enabling data integration between the Tohoku Medical Megabank and DryEyeRhythm database. The primary outcome will assess the association between genetic polymorphisms and DED using a genome-wide association study. Secondary outcomes will explore associations between DED and various factors, including sociodemographic characteristics, lifestyle habits, medical history, biospecimen analyses (eg, blood and urine), and physiological measurements (eg, height, weight, and eye examination results). Associations will be evaluated using logistic regression analysis, adjusting for potential confounding factors. RESULTS: The discovery stage of participant enrollment was conducted from August 1, 2021, to June 30, 2022. The replication stage will take place from August 31, 2024, to March 31, 2026. Data analysis is expected to be completed by September 2026, with results reported by March 2027. CONCLUSIONS: This study highlights the potential of smartphone apps in advancing biobank research and deepening the understanding of multifactorial DED, paving the way for personalized treatment strategies in the future. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/67862.
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年4月17日
出版者・発行元： 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.
Returning genetic risk information for hereditary cancers to participants in a population-based cohort study in Japan. 国際誌

Kinuko Ohneda, Yoichi Suzuki, Yohei Hamanaka, Shu Tadaka, Muneaki Shimada, Junko Hasegawa-Minato, Masanobu Takahashi, Nobuo Fuse, Fuji Nagami, Hiroshi Kawame, Tomoko Kobayashi, Yumi Yamaguchi-Kabata, Kengo Kinoshita, Tomohiro Nakamura, Soichi Ogishima, Kazuki Kumada, Hisaaki Kudo, Shin-Ichi Kuriyama, Yoko Izumi, Ritsuko Shimizu, Mikako Tochigi, Tokiwa Motonari, Hideki Tokunaga, Atsuo Kikuchi, Atsushi Masamune, Yoko Aoki, Chikashi Ishioka, Takanori Ishida, Masayuki Yamamoto

Journal of human genetics　70　(3)　147-157　2025年3月

DOI： 10.1038/s10038-024-01314-w 　

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Large-scale population cohort studies that collect genomic information are tasked with returning an assessment of genetic risk for hereditary cancers to participants. While several studies have applied to return identified genetic risks to participants, comprehensive surveys of participants' understanding, feelings, and behaviors toward cancer risk remain to be conducted. Here, we report our experience and surveys of returning genetic risks to 100 carriers of pathogenic variants for hereditary cancers identified through whole genome sequencing of 50 000 individuals from the Tohoku Medical Megabank project, a population cohort study. The participants were carriers of pathogenic variants associated with either hereditary breast and ovarian cancer (n = 79, median age=41) or Lynch syndrome (n = 21, median age=62). Of these, 28% and 38% had a history of cancer, respectively. We provided information on cancer risk, heritability, and clinical actionability to the participants in person. The comprehension assessment revealed that the information was better understood by younger (under 60 years) females than by older males. Scores on the cancer worry scale were positively related to cancer experiences and general psychological distress. Seventy-one participants were followed up at Tohoku University Hospital; six females underwent risk-reducing surgery triggered by study participation and three were newly diagnosed with cancer during surveillance. Among first-degree relatives of hereditary breast and ovarian cancer carriers, participants most commonly shared the information with daughters. This study showed the benefits of returning genetic risks to the general population and will provide insights into returning genetic risks to asymptomatic pathogenic variant carriers in both clinical and research settings.
Genome-Wide Association Study of Intraocular Pressure in Population-Based Cohorts in Japan: The Tohoku Medical Megabank Organization Eye Study. 国際誌

Nobuo Fuse, Hayato Anzawa, Miyuki Sakurai, Ikuko N Motoike, Satoshi Nagaie, Tomohiro Nakamura, Akiko Miyazawa, Eiichi N Kodama, Masatsugu Orui, Yohei Hamanaka, Tomoko Kobayashi, Akira Uruno, Makiko Taira, Ritsuko Shimizu, Naoki Nakaya, Mami Ishikuro, Taku Obara, Fuji Nagami, Soichi Ogishima, Fumiki Katsuoka, Kazuki Kumada, Shinichi Kuriyama, Atsushi Hozawa, Yoko Izumi, Kengo Kinoshita, Masayuki Yamamoto

Ophthalmology science　5　(5)　100821-100821　2025年

DOI： 10.1016/j.xops.2025.100821 　

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PURPOSE: This study was conducted to elucidate the distribution and determinants of ocular biometric parameters and to assess the association between intraocular pressure (IOP) and single nucleotide polymorphisms (SNPs) in the Japanese population-based genome cohort studies. DESIGN: Cross-sectional analysis involving genome-wide association studies (GWASs). PARTICIPANTS: In total, 22 150 participants aged >18 years from the population cohort (Community-Based Cohort [CommCohort]) and 11 302 participants from the Birth and Three-Generation (BirThree) Cohort of the Tohoku Medical Megabank Organization Eye Study were examined. METHODS: Participant underwent interviews, ophthalmic and physiological examinations, laboratory tests, and microarray analyses. Genome-wide association studies were conducted in the CommCohort (discovery stage) and the BirThree Cohort (replication stage), followed by a meta-analysis. Associations of SNPs and IOP were evaluated using a genome-wide significance threshold (5 × 10- 8). MAIN OUTCOME MEASURES: Association of SNPs with IOP and distributions of IOP by sex and age. RESULTS: In the discovery stage, the mean IOP of the right and left eye was 13.95 and 14.02 mmHg, respectively. In the replication stage, the corresponding values were 14.32 and 14.27 mmHg, respectively. A significant age-related reduction in IOP was observed in both stages (P < 0.001). Genome-wide association studies identified 573 and 2 genome-wide significant SNPs in the discovery and replication stages, respectively. Meta-analysis revealed 1601 significant SNPs across 21 loci on 11 chromosomes (Chrs). Of these loci, 17 were previously known to be associated with IOP or glaucoma, while four-septin-8 (SEPT8; Chr5), aldehyde dehydrogenase 2 (ALDH2; Chr12), collagen type VI alpha 2 chain (COL6A2; Chr21), and Wnt family member 7B (WNT7B; Chr22)-were newly identified. CONCLUSIONS: This large-scale GWAS in a Japanese population identified 21 loci associated with IOP, including 4 novel loci. The findings highlight both genetic similarities and population-specific variations in SNPs influencing IOP and provide valuable insights to enhance eye health care, including glaucoma management. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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年7月16日

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.
Sequential Sampling of the Gastrointestinal Tract to Characterize the Entire Digestive Microbiome in Japanese Subjects. 国際誌

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年6月28日

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.
Activation of NOTCH signaling impedes cell proliferation and survival in acute megakaryoblastic leukemia. 国際誌

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年6月13日

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.
The Significance of Bile in the Biliopancreatic Limb on Metabolic Improvement After Duodenal-Jejunal Bypass. 国際誌

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年5月

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.
Intracanal microbiome profiles of two apical periodontitis cases in one patient: A comparison with saliva and plaque profiles. 国際誌査読有り

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

Clinical and experimental dental research　10　(2)　e862　2024年4月

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.
Strain-dependent modifiers exacerbate familial leukemia caused by GATA1-deficiency. 国際誌

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

Experimental hematology & oncology　13　(1)　23-23　2024年2月26日

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.
The abundance of the short GATA1 isoform affects megakaryocyte differentiation and leukemic predisposition in mice. 国際誌

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

Experimental hematology & oncology　13　(1)　24-24　2024年2月26日

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.
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年2月24日

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.
[GATA factor-related hematopoietic neoplasms].

Ritsuko Shimizu

[Rinsho ketsueki] The Japanese journal of clinical hematology　65　(9)　902-910　2024年

DOI： 10.11406/rinketsu.65.902 　

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GATA1, GATA2, and GATA3, collectively known as hematopoietic GATA factors, play a central role in the transcription factor network that governs hematopoietic homeostasis. Dysfunction of these factors leads to various hematopoietic disorders. Aberrant function of GATA1 factor, crucial in erythrocyte and megakaryocyte differentiation, not only causes anemia and thrombocytopenia, but also triggers erythroid leukemia and acute megakaryoblastic leukemia. Similarly, GATA2 factor expression is dynamic in the hematopoietic hierarchy, and dysfunction of GATA2 factor contributes not only to dysfunction of the myeloid and lymphoid lineages but also to the development of diverse hematopoietic neoplasms such as myelodysplastic syndromes, acute myeloid leukemia, and myeloproliferative neoplasms. GATA3, critical for T-lymphocyte differentiation, is relevant to lymphocytic leukemia. This review discusses hematopoietic disorders caused by aberrant GATA transcription functions, with a particular emphasis on hematopoietic malignancies.
jMorp: Japanese Multi-Omics Reference Panel update report 2023. 国際誌査読有り

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年11月1日

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.
Nrf2 alleviates spaceflight-induced immunosuppression and thrombotic microangiopathy in mice 査読有り

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年8月

DOI： 10.1038/s42003-022-03316-w 　
Tohoku Medical Megabank Brain Magnetic Resonance Imaging Study: Rationale, Design, and Background 査読有り

JMA Journal　6　(3)　246-264　2023年7月
出版者・発行元：
DOI： 10.31662/jmaj.2022-0220 　

ISSN：2433-328X

eISSN：2433-3298
Recent progress in analyses of GATA1 in hematopoietic disorders: a mini-review 査読有り

Ritsuko Shimizu, Masayuki Yamamoto

Frontiers in Hematology　2　2023年5月3日
出版者・発行元： 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.
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. 査読有り

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年1月20日

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.
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年

ISSN：2758-2094
Heterozygous variants in GATA2 contribute to DCML deficiency in mice by disrupting tandem protein binding 査読有り

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

Communications Biology　5　(1)　2022年12月
出版者・発行元： 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 (G2^R398W/+), 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 G2^R398W 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, G2^R398W 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.
Characterization and Demonstration of Mock Communities as Control Reagents for Accurate Human Microbiome Community Measurements. 国際誌査読有り

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年4月27日

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.
Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan 国際誌査読有り

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年3月
出版者・発行元： 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.
Loss of Atg2b and Gskip Impairs the Maintenance of the Hematopoietic Stem Cell Pool Size. 国際誌査読有り

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年1月20日

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.
dbTMM: an integrated database of large-scale cohort, genome and clinical data for the Tohoku Medical Megabank Project. 国際誌査読有り

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年12月10日

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.
Nrf2 plays a critical role in the metabolic response during and after spaceflight. 国際誌査読有り

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年12月9日

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.
Gene expression changes related to bone mineralization, blood pressure and lipid metabolism in mouse kidneys after space travel 査読有り

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年11月
出版者・発行元： Elsevier BV
DOI： 10.1016/j.kint.2021.09.031 　

ISSN：0085-2538
Blockade of the interaction between BMP9 and endoglin on erythroid progenitors promotes erythropoiesis in mice 査読有り

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

Genes to Cells　2021年8月12日
出版者・発行元： Wiley
DOI： 10.1111/gtc.12887 　

ISSN：1356-9597

eISSN：1365-2443
Nrf2 contributes to the weight gain of mice during space travel. 国際誌査読有り

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年9月8日

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.
A non-mosaic transchromosomic mouse model of down syndrome carrying the long arm of human chromosome 21. 国際誌査読有り

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年6月29日

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.
Cohort Profile: Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study): rationale, progress and perspective. 国際誌査読有り

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年2月1日

DOI： 10.1093/ije/dyz169 　

ISSN：0300-5771
Study profile of The Tohoku Medical Megabank Community-Based Cohort Study. 査読有り

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年1月11日

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.
Oral Microbiome Analysis in Prospective Genome Cohort Studies of the Tohoku Medical Megabank Project. 国際誌査読有り

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年

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.
Design and Progress of Oral Health Examinations in the Tohoku Medical Megabank Project 査読有り

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年
出版者・発行元： Tohoku University Medical Press
DOI： 10.1620/tjem.251.97 　

ISSN：0040-8727

eISSN：1349-3329
Quantitative and qualitative impairments in GATA2 and myeloid neoplasms. 査読有り

Shimizu R, Yamamoto M

IUBMB life　2019年11月

DOI： 10.1002/iub.2188 　

ISSN：1521-6543
Establishment of Integrated Biobank for Precision Medicine and Personalized Healthcare: The Tohoku Medical Megabank Project. 査読有り

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年9月

DOI： 10.31662/jmaj.2019-0014. 　
Generation and Molecular Characterization of Human Ring Sideroblasts: a Key Role of Ferrous Iron in Terminal Erythroid Differentiation and Ring Sideroblast Formation. 国際誌査読有り

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年4月

DOI： 10.1128/MCB.00387-18 　

ISSN：0270-7306
GATA2 hypomorphism induces chronic myelomonocytic leukemia in mice. 査読有り

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

Cancer science　110　(4)　1183-1193　2019年4月

DOI： 10.1111/cas.13959 　

ISSN：1347-9032
Genome analyses for the Tohoku Medical Megabank Project towards establishment of personalized healthcare. 国際誌査読有り

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年2月1日

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.
A Gata3 3' distal otic vesicle enhancer directs inner ear-specific Gata3 expression. 国際誌査読有り

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年8月

DOI： 10.1128/MCB.00302-18 　

ISSN：0270-7306
Effects of in vivo deletion of GATA2 in bone marrow stromal cells 査読有り

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年12月

DOI： 10.1016/j.exphem.2017.08.004 　

ISSN：0301-472X

eISSN：1873-2399
Induction of erythropoietin gene expression in epithelial cells by chemicals identified in GATA inhibitor screenings 査読有り

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

GENES TO CELLS　22　(11)　939-952　2017年11月

DOI： 10.1111/gtc.12537 　

ISSN：1356-9597

eISSN：1365-2443
Prolyl isomerase Pin1 promotes proplatelet formation of megakaryocytes via tau 査読有り

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

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

DOI： 10.1016/j.bbrc.2017.09.115 　

ISSN：0006-291X

eISSN：1090-2104
Reducing Inflammatory Cytokine Production from Renal Collecting Duct Cells by Inhibiting GATA2 Ameliorates Acute Kidney Injury 査読有り

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年11月

DOI： 10.1128/MCB.00211-17 　

ISSN：0270-7306

eISSN：1098-5549
【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年8月
出版者・発行元： (株)最新医学社
ISSN：0370-8241
Renal Anemia Model Mouse Established by Transgenic Rescue with an Erythropoietin Gene Lacking Kidney-Specific Regulatory Elements. 国際誌査読有り

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

Molecular and cellular biology　37　(4)　2017年2月15日

DOI： 10.1128/MCB.00451-16 　

ISSN：0270-7306

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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.
GATA1 activity governed by configurations of cis-acting elements 招待有り査読有り

Atsushi Hasegawa, Ritsuko Shimizu

Frontiers in Oncology　6　269　2017年1月9日
出版者・発行元： Frontiers Media S.A.
DOI： 10.3389/fonc.2016.00269 　

ISSN：2234-943X
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年

ISSN：1344-6940
Monitoring of minimal residual disease in early T-cell precursor acute lymphoblastic leukaemia by next-generation sequencing 査読有り

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年1月

DOI： 10.1111/bjh.13948 　

ISSN：0007-1048

eISSN：1365-2141
The Tohoku Medical Megabank Project: Design and Mission 査読有り

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年9月

DOI： 10.2188/jea.JE20150268 　

ISSN：0917-5040
GATA1 Binding Kinetics on Conformation-Specific Binding Sites Elicit Differential Transcriptional Regulation 査読有り

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年8月

DOI： 10.1128/MCB.00017-16 　

ISSN：0270-7306

eISSN：1098-5549
GATA-related hematologic disorders 招待有り査読有り

Ritsuko Shimizu, Masayuki Yamamoto

EXPERIMENTAL HEMATOLOGY　44　(8)　696-705　2016年8月

DOI： 10.1016/j.exphem.2016.05.010 　

ISSN：0301-472X

eISSN：1873-2399
GATA2 regulates dendritic cell differentiation 査読有り

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年7月

DOI： 10.1182/blood-2016-02-698118 　

ISSN：0006-4971

eISSN：1528-0020
Unique cistrome defined as CsMBE is strictly required for Nrf2-sMaf heterodimer function in cytoprotection 査読有り

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年2月

DOI： 10.1016/j.freeradbiomed.2015.12.005 　

ISSN：0891-5849

eISSN：1873-4596
Phylogeny and Ontogeny of Erythropoiesis 査読有り

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

BIOMED RESEARCH INTERNATIONAL　2015　136270　2015年

DOI： 10.1155/2015/136270 　

ISSN：2314-6133

eISSN：2314-6141
GATA2 regulates differentiation of bone marrow-derived mesenchymal stem cells 査読有り

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年11月

DOI： 10.3324/haematol.2014.105692 　

ISSN：0390-6078
Conformational Change in Transfer RNA Is an Early Indicator of Acute Cellular Damage 査読有り

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年10月

DOI： 10.1681/ASN.2013091001 　

ISSN：1046-6673

eISSN：1533-3450
Down syndrome-associated haematopoiesis abnormalities created by chromosome transfer and genome editing technologies 査読有り

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年8月

DOI： 10.1038/srep06136 　

ISSN：2045-2322
PGC-1 Coactivator Activity Is Required for Murine Erythropoiesis 査読有り

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年6月

DOI： 10.1128/MCB.00247-14 　

ISSN：0270-7306

eISSN：1098-5549
A Remote GATA2 Hematopoietic Enhancer Drives Leukemogenesis in inv(3)(q21;q26) by Activating EVI1 Expression 査読有り

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

CANCER CELL　25　(4)　415-427　2014年4月

DOI： 10.1016/j.ccr.2014.02.008 　

ISSN：1535-6108

eISSN：1878-3686
Keap1-Nrf2 system regulates cell fate determination of hematopoietic stem cells 査読有り

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

GENES TO CELLS　19　(3)　239-253　2014年3月

DOI： 10.1111/gtc.12126 　

ISSN：1356-9597

eISSN：1365-2443
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年

ISSN：1344-6940
GATA factor switching from GATA2 to GATA1 contributes to erythroid differentiation 査読有り

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年11月

DOI： 10.1111/gtc.12086 　

ISSN：1356-9597

eISSN：1365-2443
Verification of the in vivo activity of three distinct cis-acting elements within the Gata1 gene promoter-proximal enhancer in mice 査読有り

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

GENES TO CELLS　18　(11)　1032-1041　2013年11月

DOI： 10.1111/gtc.12096 　

ISSN：1356-9597

eISSN：1365-2443
Loss of a Rho-Regulated Actin Nucleator, mDia2, Impairs Cytokinesis during Mouse Fetal Erythropoiesis 査読有り

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年11月

DOI： 10.1016/j.celrep.2013.10.021 　

ISSN：2211-1247
Establishment of erythroleukemic GAK14 cells and characterization of GATA1 N-terminal domain 査読有り

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年10月

DOI： 10.1111/gtc.12084 　

ISSN：1356-9597 1365-2443
The performance of Tohoku University on the innovation of academically driven drug discovery using chemical library 査読有り

Sugawara Akira, Aoki Junken, Dan Takashi, Shimizu Ritsuko, Suzuki Norio, Kano Kuniyuki, Okudaira Shinichi, Hakoda Akiko, Kaneko Hiroshi, Uchida Takafurni, Nakazawa Toru, Doi Takayuki, Miyata Toshio, Oshima Yoshiteru, Yamamoto Masayuki

JOURNAL OF PHARMACOLOGICAL SCIENCES　121　50P　2013年

ISSN：1347-8613
Hes repressors are essential regulators of hematopoietic stem cell development downstream of notch signaling 査読有り

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年1月

DOI： 10.1084/jem.20120993 　

ISSN：0022-1007 1540-9538
Naturally occurring oncogenic GATA1 mutants with internal deletions in transient abnormal myelopoiesis in Down syndrome 査読有り

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年
出版者・発行元： American Society of Hematology
DOI： 10.1182/blood-2012-01-405746 　

ISSN：1528-0020 0006-4971
Contribution of GATA1 dysfunction to multi-step leukemogenesis 招待有り査読有り

Ritsuko Shimizu, Masayuki Yamamoto

Cancer Science　103　(12)　2039-2044　2012年12月

DOI： 10.1111/cas.12007 　

ISSN：1347-9032 1349-7006
UG4 Enhancer-Driven GATA-2 and Bone Morphogenetic Protein 4 Complementation Remedies the CAKUT Phenotype in Gata2 Hypomorphic Mutant Mice 査読有り

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年6月

DOI： 10.1128/MCB.06699-11 　

ISSN：0270-7306
N- and C-terminal Transactivation Domains of GATA1 Protein Coordinate Hematopoietic Program 査読有り

Hiroshi Kaneko, Eri Kobayashi, Masayuki Yamamoto, Ritsuko Shimizu

JOURNAL OF BIOLOGICAL CHEMISTRY　287　(25)　21439-21449　2012年6月

DOI： 10.1074/jbc.M112.370437 　

ISSN：0021-9258
Mature erythrocyte membrane homeostasis is compromised by loss of the GATA1-FOG1 interaction 査読有り

Atsushi Hasegawa, Ritsuko Shimizu, Narla Mohandas, Masayuki Yamamoto

BLOOD　119　(11)　2615-2623　2012年3月

DOI： 10.1182/blood-2011-09-382473 　

ISSN：0006-4971
Protective role of Nrf2 in age-related hearing loss and gentamicin ototoxicity 査読有り

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年11月

DOI： 10.1016/j.bbrc.2011.10.019 　

ISSN：0006-291X
The Ufm1-activating enzyme Uba5 is indispensable for erythroid differentiation in mice 査読有り

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年2月

DOI： 10.1038/ncomms1182 　

ISSN：2041-1723
Transcriptional regulation by GATA1 and GATA2 during erythropoiesis 招待有り査読有り

Mikiko Suzuki, Ritsuko Shimizu, Masayuki Yamamoto

INTERNATIONAL JOURNAL OF HEMATOLOGY　93　(2)　150-155　2011年2月

DOI： 10.1007/s12185-011-0770-6 　

ISSN：0925-5710
Nrf2 and selenoproteins are essential for maintaining oxidative homeostasis in erythrocytes and protecting against hemolytic anemia 査読有り

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

BLOOD　117　(3)　986-996　2011年1月

DOI： 10.1182/blood-2010-05-285817 　

ISSN：0006-4971
Dual-Color Luciferase Mouse Directly Demonstrates Coupled Expression of Two Clock Genes 査読有り

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

BIOCHEMISTRY　49　(37)　8053-8061　2010年9月

DOI： 10.1021/bi100545h 　

ISSN：0006-2960
GATA factor switching during erythroid differentiation 招待有り査読有り

Hiroshi Kaneko, Ritsuko Shimizu, Masayuki Yamamoto

CURRENT OPINION IN HEMATOLOGY　17　(3)　163-168　2010年5月

DOI： 10.1097/MOH.0b013e32833800b8 　

ISSN：1065-6251
Loss of the Gata1 Gene IE Exon Leads to Variant Transcript Expression and the Production of a GATA1 Protein Lacking the N-terminal Domain 査読有り

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

JOURNAL OF BIOLOGICAL CHEMISTRY　285　(1)　773-783　2010年1月

DOI： 10.1074/jbc.M109.030726 　

ISSN：0021-9258
Induction of hyperproliferative fetal megakaryopoiesis by an N-terminally truncated GATA1 mutant 査読有り

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

GENES TO CELLS　14　(9)　1119-1131　2009年9月

DOI： 10.1111/j.1365-2443.2009.01338.x 　

ISSN：1356-9597
Direct Binding of pRb/E2F-2 to GATA-1 Regulates Maturation and Terminal Cell Division during Erythropoiesis 査読有り

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年6月

DOI： 10.1371/journal.pbio.1000123 　

ISSN：1544-9173
Stem cells of GATA1-related leukemia undergo pernicious changes after 5-fluorouracil treatment. 国際誌査読有り

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

Experimental hematology　37　(4)　435-445　2009年4月

DOI： 10.1016/j.exphem.2008.12.004 　

ISSN：0301-472X
Leukemia-related transcription factor TEL/ETV6 expands erythroid precursors and stimulates hemoglobin synthesis 査読有り

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

CANCER SCIENCE　100　(4)　689-697　2009年4月

DOI： 10.1111/j.1349-7006.2009.01097.x 　

ISSN：1347-9032
GATA1関連白血病

清水律子

東北医学雑誌　121　(2)　2009年

ISSN：0040-8700
GATA1 - related leukaemias 招待有り査読有り

Ritsuko Shimizu, James Douglas Engel, Masayuki Yamamoto

NATURE REVIEWS CANCER　8　(4)　279-287　2008年4月

DOI： 10.1038/nrc2348 　

ISSN：1474-175X
Reduced BMP4 abundance in Gata2 hypomorphic mutant mice result in uropathies resembling human CAKUT 査読有り

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年2月

DOI： 10.1111/j.1365-2443.2007.01158.x 　

ISSN：1356-9597
Impairment of erythroid and megakaryocytic differentiation by a leukemia-associated and t(9;9)-derived fusion gene product, SET/TAF-I beta-CAN/NUp214 査読有り

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

JOURNAL OF CELLULAR PHYSIOLOGY　214　(2)　322-333　2008年2月

DOI： 10.1002/jcp.21199 　

ISSN：0021-9541
GATA-1の機能異常と白血病

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年

ISSN：0916-8796
In vivo promoter analysis on refeeding response of hepatic sterol regulatory element-binding protein-1c expression 査読有り

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年11月

DOI： 10.1016/j.bbrc.2007.08.165 　

ISSN：0006-291X

eISSN：1090-2104
GATA因子スイッチングとGATA-1関連白血病 (生化学) 査読有り

清水律子, 山本雅之

生化学　79　(10)　941-952　2007年10月

ISSN：0037-1017
Dynamic regulation of Gata factor levels is more important than their identity 査読有り

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年6月

DOI： 10.1182/blood-2006-11-060491 　

ISSN：0006-4971

eISSN：1528-0020
A Gata2 intronic enhancer confers its pan-endothelia-specific regulation 査読有り

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年5月

DOI： 10.1242/dev.001297 　

ISSN：0950-1991
GATA-1 self-association controls erythroid development in vivo 査読有り

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

JOURNAL OF BIOLOGICAL CHEMISTRY　282　(21)　15862-15871　2007年5月

DOI： 10.1074/jbc.M701936200 　

ISSN：0021-9258
Characterization of GATA-1(+) hemangioblastic cells in the mouse embryo 査読有り

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年1月

DOI： 10.1038/sj.emboj.7601480 　

ISSN：0261-4189

eISSN：1460-2075
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年

ISSN：0915-8529
Rapid turnover of GATA-2 via ubiquitin-proteasome protein degradation pathway 査読有り

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

GENES TO CELLS　10　(7)　693-704　2005年7月

DOI： 10.1111/j.1365-2443.2005.00864.x 　

ISSN：1356-9597
Graded levels of GATA-1 expression modulate survival, proliferation, and differentiation of erythroid progenitors 査読有り

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年6月

DOI： 10.1074/jbc.M500081200 　

ISSN：0021-9258
Gene expression regulation and domain function of hematopoietic GATA factors 招待有り査読有り

R Shimizu, M Yamamoto

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY　16　(1)　129-136　2005年2月

DOI： 10.1016/j.semcdb.2004.11.001 　

ISSN：1084-9521
Transgenic over-expression of GATA-1 mutant lacking N-finger domain causes hemolytic syndrome in mouse erythroid cells 査読有り

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年1月

DOI： 10.1111/j.1365-2443.2005.00814.x 　

ISSN：1356-9597
Leukemogenesis caused by incapacitated GATA-1 function 査読有り

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年12月

DOI： 10.1128/MCB.24.24.10814-10825.2004 　

ISSN：0270-7306
Transgenic rescue of GATA-1-deficient mice with GATA-1 lacking a FOG-1 association site phenocopies patients with X-linked thrombocytopenia 査読有り

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

BLOOD　103　(7)　2560-2567　2004年4月

DOI： 10.1182/blood-2003-07-2514 　

ISSN：0006-4971
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年

ISSN：0910-0474
A minigene containing four discrete cis elements recapitulates GATA-1 gene expression in vivo 査読有り

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

GENES TO CELLS　7　(12)　1243-1254　2002年12月

DOI： 10.1046/j.1365-2443.2002.00595.x 　

ISSN：1356-9597
Elimination of Pasteurella pneumotropica from a contaminated mouse colony by oral administration of enrofloxacin 査読有り

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年7月

DOI： 10.1538/expanim.51.401 　

ISSN：1341-1357
Essential and instructive roles of GATA factors in eosinophil development 査読有り

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年6月

DOI： 10.1084/jem.20020170 　

ISSN：0022-1007
A functional role of Stat3 in in vivo megakaryopoiesis 招待有り査読有り

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年5月

DOI： 10.1182/blood.V99.9.3220 　

ISSN：0006-4971
Effect of growth factors on ex vivo bone marrow cell expansion using three-dimensional matrix support 査読有り

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

ARTIFICIAL ORGANS　26　(4)　333-339　2002年4月

DOI： 10.1046/j.1525-1594.2002.06842.x 　

ISSN：0160-564X
In vivo requirements for GATA-1 functional domains during primitive and definitive erythropoiesis 査読有り

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

EMBO JOURNAL　20　(18)　5250-5260　2001年9月

DOI： 10.1093/emboj/20.18.5250 　

ISSN：0261-4189
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年

ISSN：0485-1439
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年

ISSN：1345-2266
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 査読有り

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

INTERNATIONAL JOURNAL OF HEMATOLOGY　73　(1)　78-83　2001年1月

ISSN：0925-5710
GATA factor transgenes under GATA-1 locus control rescue germline GATA-1 mutant deficiencies 査読有り

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年8月

ISSN：0006-4971
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査読有り

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年1月
出版者・発行元：日本臨床血液学会
DOI： 10.11406/rinketsu.41.8 　

ISSN：0485-1439
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 査読有り

R Shimizu, N Komatsu, Y Miura

EXPERIMENTAL HEMATOLOGY　27　(2)　229-233　1999年2月

DOI： 10.1016/S0301-472X(98)00048-4 　

ISSN：0301-472X
当科における60歳以上の急性白血病の臨床的検討査読有り

田端雅彦, 吉田稔, 和泉透, 川野千鶴, 栗原亮子, 外島正樹, 大嶺謙, 高徳正昭, 内田美栄, 桐戸敬太, 宮里彰, 高橋弘憲, 星野充明, 照井康仁, 冨塚浩, 大月哲也, 清水律子, 角田純一, 室井一男, 古川雄祐, 雨宮洋一, 今川重彦, 小松則夫, 鈴木俊之, 佐々木龍平, 畠清彦, 三浦恭定

臨床血液　39　(3)　176-184　1998年3月
出版者・発行元：日本臨床血液学会
DOI： 10.11406/rinketsu.39.176 　

ISSN：0485-1439
In vitro development of erythroid and megakaryocytic cells from a UT-7 subline, UT-7/GM 査読有り

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

BLOOD　89　(11)　4021-4033　1997年6月

ISSN：0006-4971
Tec protein-tyrosine kinase is involved in the thrombopoietin/c-Mpl signaling pathway 査読有り

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

EXPERIMENTAL HEMATOLOGY　25　(3)　211-216　1997年3月

ISSN：0301-472X
Identification of functional domains of the human thrombopoietin receptor required for growth and differentiation of megakaryocytic cells 査読有り

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

JOURNAL OF BIOLOGICAL CHEMISTRY　272　(11)　7259-7263　1997年3月

DOI： 10.1074/jbc.272.11.7259 　

ISSN：0021-9258
Protein kinase C and c-myc gene activation pathways in thrombopoietin signal transduction 査読有り

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年2月

DOI： 10.1006/bbrc.1996.5969 　

ISSN：0006-291X
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

清水律子, 小松則夫

モダンフィジシャン　17　(10)　1997年

ISSN：0913-7963
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

清水律子

臨床免疫　29　(4)　1997年

ISSN：0386-9695
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

高徳正昭, 清水律子

臨床血液　38　(3)　1997年

ISSN：0485-1439
Role of c-jun in the inhibition of erythropoietin receptor-mediated apoptosis 査読有り

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

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　222　(1)　1-6　1996年5月

DOI： 10.1006/bbrc.1996.0688 　

ISSN：0006-291X
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

清水律子, 小松則夫

臨床血液　37　(7)　1996年

ISSN：0485-1439
濾胞性リンパ腫自験例21例の検討査読有り

和泉透, 今川重彦, 室井一男, 清水律子, 高橋弘憲, 星野充明, 冨塚浩, 河上利則, 戸谷公比古, 倉田寛一, 角田純一, 古川祐介, 鈴木俊之, 小松則夫, 大坂顯通, 雨宮洋一, 高木省治郎, 吉田稔, 佐々木龍平, 畠清彦, 三浦恭定

臨床血液　37　(1)　7-13　1996年1月
出版者・発行元：日本臨床血液学会
DOI： 10.11406/rinketsu.37.7 　

ISSN：0485-1439
Hepatitis C virus infection in Waldenstrom's macroglobulinemia [6] 査読有り

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

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

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

ISSN：0361-8609
Combination chemotherapy of carboplatin and cytosine arabinoside for high-risk leukemia: A pilot study 査読有り

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年12月

ISSN：0145-2126
ERYTHROPOIETIN INDUCES TYROSINE PHOSPHORYLATION AND ACTIVATION OF PHOSPHOLIPASE C-GAMMA-1 IN A HUMAN ERYTHROPOIETIN-DEPENDENT CELL-LINE 査読有り

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

JOURNAL OF BIOLOGICAL CHEMISTRY　269　(30)　19633-19638　1994年7月

ISSN：0021-9258
特集 MRSA感染症対策とG-CSF 2. 血液病とMRSAの治療と対策臨床例 VI

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年

ISSN：0917-5776

︎全件表示 ︎最初の5件までを表示

MISC 69

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年9月
出版者・発行元： (一社)日本血液学会
GATA転写因子群と血液疾患

清水律子

臨床血液　61　(9)　2020年

ISSN： 0485-1439
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年9月
出版者・発行元： (一社)日本血液学会-東京事務局
ISSN： 0485-1439

eISSN： 1882-0824
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年6月

ISSN： 0390-6078
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年6月
出版者・発行元：医薬ジャーナル社
ISSN： 1344-6940
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年8月
出版者・発行元： (有)科学評論社
ISSN： 2185-582X
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年12月

ISSN： 0006-4971

eISSN： 1528-0020
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年12月

ISSN： 0006-4971

eISSN： 1528-0020
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・日本分子生物学会年会合同大会講演要旨集　88回・38回　[4T5L-10(3P0698)]　2015年12月
出版者・発行元： (公社)日本生化学会
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年3月
出版者・発行元： (公社)日本薬学会
ISSN： 0918-9823
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年10月

ISSN： 0962-8819

eISSN： 1573-9368
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年6月

ISSN： 0390-6078
【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年3月
出版者・発行元： (株)医薬ジャーナル社
ISSN： 1344-6940
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年
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年11月

ISSN： 0006-4971
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年11月

ISSN： 0006-4971
Two Distinct Transactivation Domains of GATA1 Contribute Megakaryopoiesis

Hiroshi Kaneko, Eri Kobayashi, Ritsuko Shimizu, Masayuki Yamamoto

BLOOD　118　(21)　1451-1451　2011年11月

ISSN： 0006-4971
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) 招待有り

清水律子

臨床血液　52　(8)　695-702　2011年8月
出版者・発行元：一般社団法人日本血液学会
DOI： 10.11406/rinketsu.52.695 　

ISSN： 0485-1439
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年5月
出版者・発行元： (公財)大阪癌研究会
GATA1転写因子の機能異常と白血病

清水律子

臨床血液　52　(8)　2011年

ISSN： 0485-1439
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年12月
出版者・発行元：東北医学会
ISSN： 0040-8700
Spherocytic Hemolytic Anemia Caused by Disruption of GATA1-FOG1 Interaction

Ritsuko Shimizu, Atsushi Hasegawa, Masayuki Yamamoto

BLOOD　114　(22)　321-321　2009年11月

ISSN： 0006-4971
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年11月

ISSN： 0006-4971
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年7月
出版者・発行元：東北大学医学部保健学科
ISSN： 1348-8899
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年

ISSN： 1348-8899
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年11月

ISSN： 0006-4971
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年3月

ISSN： 0916-8796
Leukemia-related transcription factor TEL expands erythroid precursors 査読有り

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

BLOOD　110　(11)　108B-108B　2007年11月

ISSN： 0006-4971
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年10月
出版者・発行元： (公社)日本生化学会
ISSN： 0037-1017
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年8月
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年4月
出版者・発行元： (一社)日本糖尿病学会
ISSN： 0021-437X
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年3月

DOI： 10.1016/j.bcmd.2006.10.117 　

ISSN： 1079-9796
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年3月

DOI： 10.1016/j.bcmd.2006.10.125 　

ISSN： 1079-9796
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年3月

DOI： 10.1016/j.bcmd.2006.10.128 　

ISSN： 1079-9796
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年3月

DOI： 10.1016/j.bcmd.2006.10.153 　

ISSN： 1079-9796
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年

ISSN： 0037-1017
【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年6月
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年11月

ISSN： 0006-4971
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

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年9月
出版者・発行元：日本臨床血液学会
【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年9月
Application of Modern Biotechnology and Mouse Genetics for the Study of Hematopoiesis 招待有り

Yamamoto M, Shimizu R

Education Program Book　157-163　2005年4月
出版者・発行元： he Joint Meeting of the 67th Annual Meeting of Japanese Society of Hematology and the 47th Annual Meeting of Japanese Society of Clinical Hematology
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年3月

ISSN： 1079-9796
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年

ISSN： 0039-2359
【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年10月
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年8月
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年

ISSN： 0039-2359
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年7月

ISSN： 1079-9796
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年12月
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年4月
出版者・発行元：日本臨床血液学会
DOI： 10.11406/rinketsu.42.233 　

ISSN： 0485-1439
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年11月

ISSN： 0006-4971
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年10月

ISSN： 1079-9796
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年10月

ISSN： 1079-9796
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年4月

ISSN： 0917-1258
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) 招待有り

清水律子, 山本雅之

日本内科学会雑誌　88　(10)　2057-2063　1999年10月
出版者・発行元： The Japanese Society of Internal Medicine
DOI： 10.2169/naika.88.2057 　

ISSN： 0021-5384

詳細を見る詳細を閉じる

血液細胞は,造血幹細胞から転写因子ネットワークの制御を受けて分化する.近年,遺伝子解析手法の進歩により,多くの転写因子が血液がん発症に関与していることが明らかとなった.白血病の病因には,転写因子機能の失調が深く関与している.そのメカニズムは, 1)通常ではほとんど発現しない転写因子が,高レベルに発現する遺伝子の調節領域に転座して高発現するようになったもの(量的変化), 2) 2つの異なった遺伝子が転座により再融合し,通常と異なった機能を持つキメラ転写因子を創り出すために発症するもの(質的変化),に大別される.このような病因の正確な理解が,正確な診断法や新しい治療法の開発に必須である.
血液細胞と転写因子

清水律子, 山本雅之

日本内科学会雑誌　88　(10)　1999年

ISSN： 0021-5384
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年11月

ISSN： 0006-4971
【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) 招待有り

清水律子, 山本雅之

内科　82　(3)　417-421　1998年9月
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年8月

ISSN： 0301-472X
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

清水律子, 山本雅之

内科　82　(3)　1998年

ISSN： 0022-1961
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年11月

ISSN： 0006-4971
【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年10月
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) 招待有り

清水律子

臨床免疫　29　(4)　448-453　1997年4月
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年3月

DOI： 10.11406/rinketsu.38.203 　
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年8月

ISSN： 0301-472X
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年8月

ISSN： 0301-472X
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年7月
出版者・発行元：一般社団法人日本血液学会
DOI： 10.11406/rinketsu.37.526 　

ISSN： 0485-1439
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年8月

ISSN： 0301-472X
エリスロポエチン受容体構造とアポトーシスに関与する癌遺伝子発現の解析 (厚生省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年
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例査読有り

清水律子

臨床血液　34　(10)　1373-1373　1993年10月

︎全件表示 ︎最初の5件までを表示

書籍等出版物 1

未来型血液治療学

小松, 則夫

中外医学社　2019年10月

ISBN: 9784498225183

講演・口頭発表等 52

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

The 51th ASH Annual Meeting,　2010年12月7日
GATA2 in Urogenital development. 招待有り

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

The 5th International Symposium on GATA factors at Tohoku University　2010年11月17日
Regulation of Gata1 gene in vivo with the cis-acting functional motifs and GATA factor switching 招待有り

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

The 5th International Symposium on GATA factors at Tohoku University　2010年11月18日
Hasegawa A, Shimizu R, Yamamoto M. 国際会議

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

International Symposium on GATA Factors　2010年11月17日
Roles of GATA1/Rb interaction in control of megakaryocyte proliferation. 国際会議

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

International Symposium on GATA factors　2010年11月17日
Identification and analysis of novel transactivation domain of transcription factor GATA1. 国際会議

Hiroshi K, Kawatani Y, Shimizu R, Yamamoto M

International Symposium on GATA factors　2010年11月17日
Regulation of Gata1 gene in vivo with the cis-acting functional motifs and GATA factor switching. 国際会議

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

International Symposium on GATA factors　2010年11月17日
Multi-step leukemogenesis caused by N-terminally truncated GATA1 mutants. 国際会議

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

International Symposium on GATA factors　2010年11月17日
Spherocytic hemolytic anemia causedby disruption of GATA1-FOG1 interaction 国際会議

Shimizu R, Hasegawa A, Yamamoto M

Conference on Hemoglobin Switching　2010年9月1日
SUMO-conjugated GATA1 and GATA Factor Switching. 国際会議

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

Conference on Hemoglobin Switching　2010年9月1日
Hemolytic Anemia Caused by Disruption of GATA1-FOG1 Interaction. 国際会議

Hasegawa A, Shimizu R, Yamamoto M

Interaction. JSH International Symposium　2010年7月16日
Compound Deficiency of Nrf2 and Selenoproteins in Hematopoietic Cells Leads to Severe Defects in Erythroid and Lymphoid Lineage Development. 国際会議

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年5月31日
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

The 51th ASH Annual Meeting,　2009年12月7日
Spherocytic hemolytic anemia caused by disruption of GATA1-FOG1 interaction.

Shimizu R, Hasegawa A, Yamamoto M

The 51th ASH Annual Meeting,　2009年12月7日
Acquired loss of IE exon of Gata1 gene causes expression of variant transcripts and leads to production of N-terminus truncated GATA1 protein. 国際会議

Shimizu R, Kobayashi EEngel JD, Yamamoto M

Red Cell Gordon Conference　2009年6月28日
GATA factor switching during erythroid differentiation 国際会議

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

Red cell Gordon Conference　2009年6月28日
Compound Deficiency of Nrf2 and Selenoproteins in Hematopoietic Cells Leads to Severe Defects in Erythroid and Lymphoid Development

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

he 51th ASH Annual Meeting,　2009年12月7日
Induction of Hyperproliferative Fetal Megakaryopoiesis by an N-terminally Truncated GATA1 Mutant 国際会議

Shimizu R, Engel JD, Yamamoto M

ASH Annual Meeting　2008年12月6日
Gata1 Gene Regulation and GATA1-related Leukemia 国際会議

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

Conference on Hemoglobin Switching　2008年10月11日
Induction of Hyperproliferative Fetal Megakaryopoiesis by an N-terminally Truncated GATA1 Mutant 国際会議

Shimizu R, Engel JD, Yamamoto M

Conference on Hemoglobin Switching　2008年10月11日
GATA-2 in Auditory and Neuronal System 国際会議

Tomofumi Hoshino, Ritsuko Shimizu, Masayuki Yamamoto, Akira Hara

Midwinter Research Meeting of Association for Research in Otolaryngology　2008年2月16日
Leukemia-related transcription factor TEL expands erythroid precursors 国際会議

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

Annual meeting of American Society of Hematology　2007年12月8日
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 招待有り

Shimizu R, Abe K, Yamamoto M

The 11th Germany-Japan Cancer Workshop　2007年11月30日
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年11月29日
Increase of hematopoietic progenitors but impairment of erythroid and megakaryocytic differentiation in transgenic mice expressing SET-CAN 国際会議

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

Stem cell Gordon Conference　2007年9月9日
Analyses of leukemic stem cells of GATA-1 related leukemia 国際会議

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

Stem cell Gordon Conference　2007年9月9日
Transcription Factor GATA-2 Regulates Self-renewal of Hematopoietic Stem Cells 国際会議

Ritsuko Shimizu, Tomofumi Hoshino, Norio Suzuki, Masayuki Yamamoto

Stem cell Gordon Conference　2007年9月9日
Sumo-modification of GATA-1 at lysine-137 is important for erythropoiesis through its ability to repress Gata2 transcription 国際会議

Shimizu R, Ohmori S, Engel JD, Yamamoto M

International Symposium on GATA Factors　2007年4月14日
Construction of transgenic mice expressing novel beetle luciferase 国際会議

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

nternational Symposium on Bioluminescence and Chemiluminescence　2006年10月15日
Dynamic regulation of gata factor levels is more important than their identity 国際会議

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年9月15日
TAL-1 and GATA-1 coupled cell proliferation and differentiation during terminal erythroid differentiation 国際会議

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年9月15日
Regulation of Mouse Gata1 Gene Expression in Erythroid Progenitors 国際会議

Masayuki Yamamoto, Mikiko Suzuk, Norio Suzuki, Ritsuko Shimizu

Hemoglobin Switching Conference　2006年9月15日
Developmental regulation ofGata1 gene expression through adjacent GATA boxes and CP2-binding sites 国際会議

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

Hemoglobin Switching Meeting　2006年9月14日
The direct association of GATA-1 to rb is necessary for definitive erythropoiesis 国際会議

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

American Society of Hematology　2005年12月8日
Gene expression regulation and domain function of hematopoietic GATA factors

Masayuki Yamamoto, Ritsuko Shimizu, Kinuko Ohneda, Norio Suzuki

apanese Biochemical Society Meeting　2005年10月19日
Establishment of GATA-1-deficient GAK14 Cells and Examination of Roles N-terminal Domain of GATA-1 Play during Erythroid Differentiation 国際会議

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

Red cell Gordon Conference　2005年6月11日
Contribution of NT Domain of GATA-1 and Runx1 to the Definitive Erythropoiesis. 国際会議

Ritsuko Shimizu, Kinuko Ohneda, Masayuki Yamamoto

Red cell Gordon Conference　2005年6月11日
Rescue of GATA1 null Mice by GATA Transgenes Requires the Correct Spatio-Temporal Expression Pattern 国際会議

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年9月10日
A New Pathway for Definitive Hematopoiesis Revealed in the Transgenic Rescue of Runx1-deficient Mouse 国際会議

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年9月10日
Self-Associationof GATA-1 is Required for Erythropoiesis In Vivo 国際会議

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

Hemoglobin Switching Meeting　2004年9月10日
Transgenic rescue of runx1-deficient mice reveals the heterogeneity of he definitive hematopoietic pathway 国際会議

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年7月17日
GATA-2 and hematopoietic stem cells 国際会議

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

International Symposium on GATA Factors　2003年7月17日
Leukemogenesis caused by incapacitated GATA-1 function. The 3rd International Symposium on GATA Factors 国際会議

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

International Symposium on GATA Factors　2003年7月15日
A minigene containing four discrete cis elements recapitulates GATA-1 gene expression in vivo

The 13th Conference on Hemoglobin Switching Meeting,　2002年9月26日
Functional role of Stat3 in megakaryopoiesis: in vivo.

Keita Kirito, Masatake Ozawa, Ritsuko Shimizu, Atsushi Oda, Koichi Nakajima, Haruhiko Morita, Masayuki Yamamoto, Keiya Ozawa, Norio Komatsu

he 42nd Annual Meeting of the American Society of Hematology　2000年12月8日
Regulation of the murine GATA-2 and GATA-3 gene. 招待有り

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年11月18日
Functional GATA-1 domain analysis with transgenic rescue of germ line GATA-1 mutant mouse.

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

The 2nd International Symposium on GATA factors “GATA Factor Functions in Development”　2000年11月18日
Regulation and domain function analyses of GATA-1 and GATA-2 招待有り

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年11月19日
Functional GATA-1 domain analysis with transgenic rescue of germ line GATA-1 mutant deficiencies.

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

The 12th Conference on Hemoglobin Switching Meeting,　2000年6月9日
Regulation of Mouse GATA-1 and GATA-2 Gene 招待有り

Shimizu R, Yamamoto M

The 12th Conference on Hemoglobin Switching　2000年6月11日
Dominant negative effect of a truncated erythropoietin receptor on erythropoietin-induced erythroid differentiation.

The 39th Annual Meeting of the American Society of Hematology　1997年12月6日
Role of c-Jun in the inhibition of apoptosis through the erythropoietin receptor.

24th Annual Meeting of the International Society for Experimental Hematology,　1995年8月29日

︎全件表示 ︎最初の5件までを表示

共同研究・競争的資金等の研究課題 2

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

2019年4月1日～ 2023年3月31日

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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。
血球分化の分子機構と臨床的解析競争的資金

小松則夫

1997年4月～ 2000年3月

担当経験のある科目(授業) 3

輸血学　筑波大学、東北大学
医化学　筑波大学、東北大学
血液学　東北大学

その他 7

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
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
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
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
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
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
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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