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Affiliation |
Faculty of Medicine School of Medicine Department of Internal Medicine, Hematology, Diabetes, and Endocrinology |
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Professor |
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External Link |
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SHIMODA Kazuya
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Degree 【 display / non-display 】
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博士（医学） ( 1994.5 九州大学 )
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医学士 ( 1987.3 九州大学 )
Research Areas 【 display / non-display 】
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Life Science / Hematology and medical oncology
Papers 【 display / non-display 】
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Usuki K., Kameda T., Kawano N., Ito T., Hashimoto Y., Shide K., Kawano H., Sekine M., Toyama T., Iizuka H., Sato S., Takeuchi M., Ishizaki J., Maeda K., Nakai M., Yamashita K., Kubuki Y., Shimoda K.
International Journal of Hematology 2024.3
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
Myeloid and lymphoid neoplasms associated with FGFR1 abnormalities (MLN-FGFR1 abnormalities) are rare hematologic malignancies associated with chromosome 8p11.2 abnormalities. Translocations of 8p11.2 were detected in 10 of 17,039 (0.06%) unique patient cytogenetic studies performed at nine institutions in Japan. No inversions or insertions of 8p11.2 were detected. Among the 10 patients with 8p11.2 translocations, three patients were diagnosed with MLN-FGFR1 abnormalities, which were confirmed by FISH analysis. Peripheral blood eosinophilia was observed in all three patients, and all progressed to AML or T-lymphoblastic lymphoma/leukemia. The prevalence of 8p11.2 translocations in clinical practice and the proportion of MLN-FGFR1 abnormalities in patients with 8p11.2 translocations in Japan were consistent with those in previous reports from Western countries.
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Ichikawa T., Suekane A., Nakahata S., Iha H., Shimoda K., Murakami T., Morishita K.
International Journal of Molecular Sciences 25 ( 5 ) 2842 2024.2
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Molecular Sciences
N-myc downstream-regulated gene 2 (NDRG2), which is a tumour suppressor, is frequently lost in many types of tumours, including adult T-cell leukaemia/lymphoma (ATL). The downregulation of NDRG2 expression is involved in tumour progression through the aberrant phosphorylation of several important signalling molecules. We observed that the downregulation of NDRG2 induced the translocation of protein arginine methyltransferase 5 (PRMT5) from the nucleus to the cytoplasm via the increased phosphorylation of PRMT5 at Serine 335. In NDRG2low ATL, cytoplasmic PRMT5 enhanced HSP90A chaperone activity via arginine methylation, leading to tumour progression and the maintenance of oncogenic client proteins. Therefore, we examined whether the inhibition of PRMT5 activity is a drug target in NDRG2low tumours. The knockdown of PRMT5 and binding partner methylsome protein 50 (MEP50) expression significantly demonstrated the suppression of cell proliferation via the degradation of AKT and NEMO in NDRG2low ATL cells, whereas NDRG2-expressing cells did not impair the stability of client proteins. We suggest that the relationship between PRMT5/MEP50 and the downregulation of NDRG2 may exhibit a novel vulnerability and a therapeutic target. Treatment with the PRMT5-specific inhibitors CMP5 and HLCL61 was more sensitive in NDRG2low cancer cells than in NDRG2-expressing cells via the inhibition of HSP90 arginine methylation, along with the degradation of client proteins. Thus, interference with PRMT5 activity has become a feasible and effective strategy for promoting cancer vulnerability in NDRG2low ATL.
DOI： 10.3390/ijms25052842
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Mine K., Nagafuchi S., Akazawa S., Abiru N., Mori H., Kurisaki H., Shimoda K., Yoshikai Y., Takahashi H., Anzai K.
Nature Communications 15 ( 1 ) 1337 2024.2
Language：English Publishing type：Research paper (scientific journal) Publisher：Nature Communications
Tyrosine kinase 2 (TYK2), a member of the JAK family, has attracted attention as a potential therapeutic target for autoimmune diseases. However, the role of TYK2 in CD8+ T cells and autoimmune type 1 diabetes (T1D) is poorly understood. In this study, we generate Tyk2 gene knockout non-obese diabetes (NOD) mice and demonstrate that the loss of Tyk2 inhibits the development of autoreactive CD8+ T-BET+ cytotoxic T lymphocytes (CTLs) by impairing IL-12 signaling in CD8+ T cells and the CD8+ resident dendritic cell-driven cross-priming of CTLs in the pancreatic lymph node (PLN). Tyk2-deficient CTLs display reduced cytotoxicity. Increased inflammatory responses in β-cells with aging are dampened by Tyk2 deficiency. Furthermore, treatment with BMS-986165, a selective TYK2 inhibitor, inhibits the expansion of T-BET+ CTLs, inflammation in β-cells and the onset of autoimmune T1D in NOD mice. Thus, our study reveals the diverse roles of TYK2 in driving the pathogenesis of T1D.
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Clinical outcomes of patients with myelofibrosis after immediate transition to momelotinib from ruxolitinib. Reviewed
Mesa R, Verstovsek S, Platzbecker U, Gupta V, Lavie D, Giraldo P, Recher C, Kiladjian JJ, Oh ST, Gerds AT, Devos T, Passamonti F, Vannucchi AM, Egyed M, Lech-Maranda E, Pluta A, Nilsson L, Shimoda K, McLornan D, Kawashima J, Klencke B, Huang M, Strouse B, Harrison C
Haematologica 109 ( 2 ) 676 - 681 2024.2
Language：English Publishing type：Research paper (scientific journal)
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Impaired humoral immunity following COVID-19 vaccination in HTLV-1 carriers. Reviewed
Kameda T., Utsunomiya A., Otsuka N., Kubuki Y., Uchida T., Shide K., Kamiunten A., Nakano N., Tokunaga M., Miyazono T., Ito Y., Yonekura K., Kawakita T., Akizuki K., Tahira Y., Karasawa M., Hidaka T., Konagata A., Taniguchi N., Nagatomo Y., Kogo F., Shimizu K., Ueno H., Ishizaki J., Takahashi N., Ikei Y., Hidaka M., Yamaguchi H., Shimoda K.
BMC Infectious Diseases 24 ( 1 ) 96 2024.1
Language：English Publishing type：Research paper (scientific journal) Publisher：BMC Infectious Diseases
Background: Whether human T-lymphotropic virus type 1 (HTLV-1) carriers can develop sufficient humoral immunity after coronavirus disease 2019 (COVID-19) vaccination is unknown. Methods: To investigate humoral immunity after COVID-19 vaccination in HTLV-1 carriers, a multicenter, prospective observational cohort study was conducted at five institutions in southwestern Japan, an endemic area for HTLV-1. HTLV-1 carriers and HTLV-1-negative controls were enrolled for this study from January to December 2022. During this period, the third dose of the COVID-19 vaccine was actively administered. HTLV-1 carriers were enrolled during outpatient visits, while HTLV-1-negative controls included health care workers and patients treated by participating institutions for diabetes, hypertension, or dyslipidemia. The main outcome was the effect of HTLV-1 infection on the plasma anti-COVID-19 spike IgG (IgG-S) titers after the third dose, assessed by multivariate linear regression with other clinical factors. Results: We analyzed 181 cases (90 HTLV-1 carriers, 91 HTLV-1-negative controls) after receiving the third dose. HTLV-1 carriers were older (median age 67.0 vs. 45.0 years, p < 0.001) and more frequently had diabetes, hypertension, or dyslipidemia than did HTLV-1-negative controls (60.0% vs. 27.5%, p < 0.001). After the third dose, the IgG-S titers decreased over time in both carriers and controls. Multivariate linear regression in the entire cohort showed that time since the third dose, age, and HTLV-1 infection negatively influenced IgG-S titers. After adjusting for confounders such as age, or presence of diabetes, hypertension, or dyslipidemia between carriers and controls using the overlap weighting propensity score method, and performing weighted regression analysis in the entire cohort, both time since the third dose and HTLV-1 infection negatively influenced IgG-S titers. Conclusions: The humoral immunity after the third vaccination dose is impaired in HTLV-1 carriers; thus, customized vaccination schedules may be necessary for them.
Books 【 display / non-display 】
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イヤーノート2025 内科・外科編
下田和哉 他（ Role： Joint author , 血液学総論（造血幹細胞移植~脾摘術）、白血球系の異常(白血球増加症～骨髄異形成症候群)、白血球系の異常（悪性腫瘍リンパ腫以外の成熟B細胞腫瘍～成熟T細胞腫瘍））
株式会社メディックメディア 2024.3
Book type：Scholarly book
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別冊日本臨牀 血液症候群（第3版）ーその他の血液疾患を含めてーⅣ
亀田拓郎、幣光太郎、下田和哉（ Role： Joint author , 本態性血小板血症）
株式会社 日本臨牀社 2024.2
Responsible for pages：27-32頁 Language：Japanese Book type：Scholarly book
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血液専門医テキスト(改訂第4版)
下田和哉 他（ Role： Joint author , その他の骨髄増殖性疾患 252-254頁）
株式会社 南江堂 2023.10
Language：Japanese Book type：Textbook, survey, introduction
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造血器腫瘍診療ガイドライン2023年版
下田和哉、入山規良、川口辰哉、木村晋也、桐戸敬太、髙橋直人、竹中克斗（ Role： Joint author , 慢性骨髄性白血病/骨髄増殖性腫瘍（chronic myeloid leukemia/myeloproliferative neoplasms:CML/MPN））
金原出版 2023.7 （ ISBN:978-4-307-10224-7 ）
Total pages：484 Responsible for pages：50 Book type：Scholarly book
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イヤーノート2024 内科・外科編
下田和哉 他（ Role： Contributor , 血液学総論（造血幹細胞移植~脾摘術）、白血球系の異常(白血球増加症～骨髄異形成症候群、悪性腫瘍リンパ腫以外の成熟B細胞腫瘍～成熟T細胞腫瘍)）
株式会社メディックメディア 2023.3
Language：Japanese Book type：Scholarly book
MISC 【 display / non-display 】
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【アンメットニーズに対するJAK阻害薬の可能性】骨髄増殖性腫瘍に対するJAK阻害薬の治療効果
幣光太郎、下田和哉
炎症と免疫 32 ( 2 ) 129 - 132 2024.2
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
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治療法の再整理とアップデートのために 専門家による私の治療 原発性骨髄線維症(PMF)
下田和哉
日本医事新報 ( 5203 ) 34 - 35 2024.1
Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
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【JAK阻害薬の効果・安全性と展望】骨髄線維症,真性多血症の病態と,JAK阻害薬の効果・安全性・展望
幣光太郎、下田和哉
リウマチ科 70 ( 6 ) 608 - 614 2023.12
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
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【実診療において治療に難渋する造血器腫瘍の病態と新たな治療戦略】二次性骨髄線維症の治療 新規治療薬開発の動向も踏まえて
秋月渓一、下田和哉
血液内科 87 ( 2 ) 193 - 198 2023.8
Publishing type：Rapid communication, short report, research note, etc. (scientific journal)
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Uchida T., Ueno H., Konagata A., Taniguchi N., Kogo F., Nagatomo Y., Shimizu K., Yamaguchi H., Shimoda K.
Diabetes Therapy 14 ( 6 ) 1075 - 1076 2023.6
Language：English Publishing type：Rapid communication, short report, research note, etc. (scientific journal) Publisher：Diabetes Therapy
Presentations 【 display / non-display 】
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ネフローゼ症候群を呈した非典型的慢性GVHD
長嶺宏士朗、松本健吾、幣光太郎、秋月渓一、池田涼馬、唐澤賢祥、上運天綾子、田平優貴、亀田拓郎、久冨木庸子、下田和哉
第14回日本血液学会九州地方会 2024.3.9
Event date： 2024.3.9
Presentation type：Oral presentation (general)
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ATL新規治療標的同定と、個別化診療への展開
下田和哉
HTLV-1 関連疾患研究領域 研究班合同発表会 2024.2.17 厚生労働省 新興・再興感染症及び予防接種政策推進研究事業「HTLV-1総合対策」推進におけるキャリア対策の基盤整備と適正な研究開発の推進に資する包括的評価と提言のための研究、AMED
Event date： 2024.2.17
Presentation type：Oral presentation (general)
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NS-018, a potent novel JAK2 inhibitor,effectively treats murine MPN induced by the Janus kinase 2 (JAK2) V617F mutant. International conference
Yuki Tahira, Kotaro Shide, MD, PhD, Takuro Kameda, MD, Ayako Kamiunten, Keiichi Akizuki, MD, Masayoshi Karasawa, Ryoma Ikeda, Kengo Matsumoto, Yoko Kubuki, MD, PhD, Kazuya Shimoda, MD, PhD
The American society of Hematology 65th Annual Meeting and Exposition (San Diego, California, USA) 2023.12.11
Event date： 2023.12.9 - 2023.12.12
Language：English Presentation type：Oral presentation (general)
Venue：San Diego, California, USA Country：United States
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チルゼパチド投与3か月後にインスリン60単位/日を中止できた一例
上野浩晶、水田雅也、古郷芙美子、中村孝之、内田泰介、与那嶺真一、積島愛加理、積島宏昴、清水浩一郎、山口秀樹、下田和哉
第61回日本糖尿病学会九州地方会 2023.12.2
Event date： 2023.12.1 - 2023.12.2
Presentation type：Oral presentation (general)
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２型糖尿病に対するチルゼパチドの短期使用効果の検討
与那嶺真一、上野浩晶、古郷芙美子、中村孝之、内田泰介、積島愛加理、積島宏昴、清水浩一郎、山口秀樹、下田和哉
第61回日本糖尿病学会九州地方会 2023.12.2
Event date： 2023.12.1 - 2023.12.2
Presentation type：Oral presentation (general)
Awards 【 display / non-display 】
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日本白血病研究基金 清水賞
2002.11 日本白血病研究基金
下田和哉
Award type：Award from publisher, newspaper, foundation, etc. Country：Japan
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日本癌学会奨励賞
2002.10 日本がん学会
下田和哉
Award type：Award from Japanese society, conference, symposium, etc. Country：Japan
Grant-in-Aid for Scientific Research 【 display / non-display 】
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新規病態：HTLV-1陽性HRS細胞を伴う成人T細胞白血病/リンパ腫の統合的解析
Grant number：23H02693 2023.04 - 2027.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究（B）
Authorship：Coinvestigator(s)
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腫瘍性fibrocyteの本態解明と、骨髄線維症診断・治療への展開
Grant number：23H02938 2023.04 - 2026.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究（B）
Authorship：Principal investigator
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1007創薬に向けた、CALR変異とfibrocyteに着目する骨髄増殖性腫瘍研究
2017.04 - 2019.03
科学研究費補助金 基盤研究(B)
下田和哉、久冨木庸子、日髙智徳、幣光太郎
Authorship：Principal investigator
骨髄増殖性腫瘍(MPN)のドライバー変異であるJAK2,CALR変異が同定されMPNの病態が明らかにされつつあるが、CALR変異がMPNを発症させる機序や、骨髄線維症の本態である骨髄線維化細胞の起源、つまり間質の反応性変化なのか、あるいは腫瘍クローン由来fibrocyteなのかは不明である。本研究では以下の3つの方法により、MPNの新たな治療につながる研究を行う。
Ⅰ. MPLとの会合やSTAT活性化に必須な変異CALRの領域同定と、その阻害による治療開発
Ⅱ. 本態性血小板血症から骨髄線維症へ進展する分子イベントの同定
Ⅲ. 腫瘍クローン由来fibrocyteが骨髄線維化に果たす役割の同定と、骨髄線維化を改善することをすでに見出しているMEK阻害剤がfibrocyteに及ぼす影響の解明 -
TET2変異による造血器腫瘍の発症と進展メカニズムの解明
2014.04 - 2017.03
科学研究費補助金 基盤研究(C)
Authorship：Principal investigator
TET2変異による造血器腫瘍の発症と進展メカニズムの解明
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骨髄増殖性腫瘍における病型の進展と急性転化メカニズムの解明
2012.04 - 2015.03
科学研究費補助金 基盤研究(C)
Authorship：Coinvestigator(s)
骨髄増殖性腫瘍における病型の進展と急性転化メカニズムの解明
Past consigned research fund received 【 display / non-display 】
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A Phase 2b Open-Label Single-Arm Study to Evaluate the Efficacy and Safety of Oral HBI-8000 in Patients with Relapsed or Refractory Adult T Cell Lymphoma(ATL)
2017.01 - 2019.12
Investigational New Drug Test
Consigned research type：Investigational New Drug Test
Available Technology 【 display / non-display 】
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骨髄増殖性腫瘍、病因遺伝子の機能解析と新規治療法開発
白血病細胞のゲノム情報に基づく成人T細胞白血病の克服戦略Home Page： 内科学講座 血液・糖尿病・内分泌学分野
Related fields where technical consultation is available：・血液疾患マウスモデルの作成と解析、治療法開発への応用
・サイトカインシグナル伝達機構の解析
（共同研究が可能なテーマ）骨髄増殖性腫瘍、成人T細胞白血病を対象とした研究