MF Researcher Database

Researchers Database

Advance

IIDA Shinsuke

    Graduate School of Medical Sciences Department of Hematology & Oncology　Professor
Contact： iidamed.nagoya-cu.ac.jp
Last Updated :2024/04/24

Researcher Information

URL

J-Global ID

Research Interests

  • 分子標的療法   白血病   骨髄腫   リンパ腫   

Research Areas

  • Life sciences / Hematology and oncology

Academic & Professional Experience

  • 1991~1994 Visiting scientist, Aichi Cancer Center Research Institute, Nagoya, Japan1994~1997 Visiting scientist/Postdoctoral fellow, Department of Pathology, Columbia University, New York, NY, USA

Education

  •        - 1987  Nagoya City University  Faculty of Medicine  医学

Association Memberships

  • European Hematology Association   American Society of Hematology   日本臨床腫瘍学会   日本造血細胞移植学会   日本癌学会   日本血液学会   日本内科学会   Japanese Society of Myeloma   

Published Papers

MISC

Research Grants & Projects

  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2020/04 -2023/03 
    Author : 飯田 真介; 李 政樹
     
    本研究では、骨髄腫の病勢進行や薬剤感受性に関わる因子を同定する目的にて、骨髄および末梢血から、単核球DNAおよび血清中のcell free DNA: cfDNAを抽出し、病態や薬剤感受性に関わる遺伝子の変異を検索し、病勢の進行や治療薬の反応性との関連を調べることを目的としている。 これまでに、初発未治療の多発性骨髄腫患者さんの末梢血血清から、cfDNAを抽出し、約40-200ngほどのライブラリー作成に十分な量が得られることを確認し、得られる末梢血cfDNAの量はステージ進行や腫瘍量と相関があることを見出してきた。これまでに作成したターゲットキャプチャーシクエンスの基盤となる、多発性骨髄腫の薬剤や病態に関連する遺伝子パネルリストを用いて、実際にシークエンスを行い原データを収集を行なった。なかでも、ハイリスク染色体異常であるIgH-MAF転座症例を中心に、病態に関わる遺伝子変異を骨髄腫細胞と末梢血cfDNAの双方のdry解析を行なっている。
  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2020/04 -2023/03 
    Author : 三田 貴臣; 飯田 真介; 鈴木 智貴
     
    二年度においては、成人Ｔ細胞性白血病（ATL）、二次性形質細胞白血病（PCL）と多発性骨髄腫（MM）、びまん性大細胞性リンパ腫（DLBCL）を対象として、エンハンサー解析、遺伝子発現解析、ゲノム解析を行った。COVID-19に関連した移動制限・活動制限のため、主にデータ解析並びに予備データの作成に努めた。 まず、ATLに関して、細胞株並びに患者検体を用いた遺伝子発現解析・エンハンサープロファイリングを行い、ATL特異的に発現亢進している遺伝子を同定した。これらのうち、患者検体の多くでCD28-CTLA4、IKZF2、TP73遺伝子領域にスーパーエンハンサーが認められ、幾つかの検体では同領域に遺伝子・染色体異常を伴っていることが確認された。これら３つの遺伝子は、T細胞の発達あるいは腫瘍細胞の増殖に関与していることが知られており、スーパーエンハンサー形成並びに遺伝子異常がATLの病態と関わっていることが示唆された。一方、ATL細胞において特異的に発現している転写産物の解析も行い、新規long non-codingを同定した。これらに関して、遺伝子ノックダウンや強制発現系を用いて機能解析を行っている。 次に、PCLに関して、患者検体を用いて全ゲノム解析、遺伝子発現解析、シングルセル解析を行い、MMからPCLへ発展する段階で認められる遺伝子異常を同定した。興味深いことに、MMにおいて以前から知られている1q21領域の増幅がPCLのサンプルにて認められ、これらがPCLの病態形成、並びにクローン進化に関与している可能性が示唆された。 加えて、DLBCLの多数患者検体を用いて全エキソームシーケンス解析を行い、遺伝子異常と病態との関連性について解析を行っている。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2016/04 -2020/03 
    Author : Iida Shinsuke
     
    The purpose of this study is to explore predictive or prognostic biomarkers in blood in patients with multiple myeloma (MM). Cell free nuclear acids such as microRNA and cfDNA isolated from peripheral blood were analyzed by next generation sequencing in association with clinical information including patients’ prognosis and sensitivity to molecular targeting agents. Our study identified several serum microRNAs associated with sensitivity to bortezomib therapy. Sequential genetic analysis of cfDNAs in the same patients could identify some specific mutations relevant to the disease progression in MM. As well, serum lipid metabolites were comprehensively analyzed. It identified some lipid metabolites which might predict poor response to bortezomib plus dexamethasone therapy and occurrence of grade 2 or higher bortezomib-induced peripheral neuropathy. Further studies are needed to validate such candidate biomarkers in prospective large-scale studies.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2008 -2010 
    Author : KOMATSU Hirokazu; IIDA Shinsuke; KUSUMOTO Shigeru
     
    Individual-based management including anticipatory nausea has been shown to be critical for anti-emetic therapy in ambulatory cancer patients undergoing chemotherapy. Early oral health care can be effective for the management of chemotherapy-induced stomatitis. Skin damage by chemotherapy and molecular-targeted therapy should be managed prophylactically by the multi-disciplinary medicine. Nurses in outpatient chemotherapy center may have difficulty in assessing their patients'symptoms and supportive care needs. The total supports for their family should be essential as well as patients. Psycho-oncology, patients' education and home health care will be next focused issues.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2005 -2009 
    Author : UEDA Ryuzo; SATO Shigeki; KOMATSU Hirokazu; ISHIDA Takashi
     
    CCR4 is a chemokine receptor selectively expressed on Treg and Th2 cells. Because we previously found that CCR4 is expressed on certain types of T-cell leukemia/lymphoma, we postulated that this molecule might represent a novel molecular target for immunotherapy against refractory T-cell leukemia/lymphoma. Accordingly, we have developed a next-generation anti-CCR4 mAb, the Fc region of which is defucosylated, resulting in highly enhanced ADCC. Based on our laboratory work on CCR4, and as an outcome of the success of this translational research, we have completed phase I & II clinical trials of anti-CCR4 mAb in patients with CCR4-positive T-cell leukemia/lymphoma in Japan, and are in the process of preparing an application to the regulatory authority for approval.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2007 -2008 
    Author : HANAMYRA Ichiro; NITTA Masakazu; IIDA Shinsuke; TANIWAKI Masafumi; GOTO Mayuko; JOHN Shaughnessy
     
    ヒト骨髄腫細胞株を用いた検討では、染色体1q21領域の増加/増幅の多くは1番染色体そのものまたは長腕の増多に伴って起きたものであり、jumping/tandem translocationといった複雑な転座様式をとったものは約30%であった。未治療MM例とは異なり細胞株においては1q21の増加の有無や増幅様式の差と、13q14欠失、17p13欠失、Ig領域との染色体転座で脱制御されるCCND1やFGFR3、c-MAF、MAFBなどとの間に有意な相関は認めなかった。このことは、細胞株は進行期の病変から樹立されることが多いためと思われるが、MMにおいて1番染色体長腕その中でも特に1q21は特異な領域であることが改めて示唆された。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2005 -2006 
    Author : KOMATSU Hirokazu; UEDA Ryuzo; IIDA Shinsuke
     
    We previously reported that a dominant-positive activating mutation (Asn505) in the transmembrane domain (TMD) of c-MPL, which encodes the thrombopoietin receptor, caused familial essential thrombocythemia. Here, we show that the Asn505 mutation induces both autonomous dimerization of c-Mpl and signal activation in the absence of its ligand. Signal activation was preserved in a truncated mutant of Asn505 that lacked the extracellular domain of c-Mpl. We also found that the substitution of the amino acid (AA) residue at position 505 with others of strong polarity (Glu, Asp or Gln) also resulted in activated dimerization without ligand stimulation. Overall, these data show that the Asn505 mutation transduced the signal through the autonomous dimerization of the c-Mpl protein due to strong AA polarity. This finding provides a new insight into the mechanism of disease causation by mutations in the TMD of cytokine/hematopoietic receptors.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2004 -2006 
    Author : UEDA Ryuzo; IIDA Shinsuke; KOMATSU Hirokazu
     
    CCR4 was shown to be expressed in many types of T-cell malignancies, especially in adult T-cell leukemia/lymphoma (ATLL), peripheral T-cell lymphoma-unspecified (PTCL-U) and anaplastic large cell lymphoma (ALK negative) and be a significant and independent prognostic marker in ATLL and PTCL-U. Monoclonal antibody for CCR4 presented a strong anti-tumor effect for several types of T-cell malignancies via ADCC activity in vivo as well as in vitro assay, including CCR4-espressing Hodgkin lymphoma and cutaneous T-cell lymphoma. CCR4 was also expressed in the surface of cells with the character of regulatory T-cells (FOXP3 positive), strongly suggesting that the origin of ATLL tumor cells can be regulatory T-cells. Reactive T-cells surrounding Hodgkin cells (Reed-Sternberg cells) were shown to manifest both CCR4 and FOXP3 expressions on their surfaces, which suggest that CCR4 can be target molecule for the elimination of the anergy for tumor immunity. Phase I clinical study of the humanized monoclonal antibody therapy of CCR4 for T-cell malignancies was conducted and was shown to be well-tolerable with clinical resoponse.
  • 多発性骨髄腫における染色体転座の発症機構と腫瘍化への関与
    Date (from‐to) : 2001 -2003
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2000 -2003 
    Author : UEDA Ryuzo; IIDA Shinsuke; WAKITA Atsushi
     
    1.Identification of novel chromosomal translocations found in multiple myeloma : 1)t(1;14)(p34;q32) : 1p34 breakpoint of ODA cells was isolated by genomic cloning and found to have disrupted E3/LAPTm5 gene in terms of its expression. This phenomenon was caused by hypermethylation of the regulatory sequences of the gene. 2)t(1;14)(p34;q32) : 1p34 breakpoint of ODA cells was isolated by genomic cloning and found to have disrupted E3/LAPTm5 gene in the first intron. Interestingly, this gene was shut off in 60% of the myeloma cell lines in terms of its expression. This phenomenon was caused by hypermethylation of the regulatory sequences of the gene. 2.14q32 translocations in MGUS/smoldering multiple myeloma(SMM) Purified plasma cells derived from 16 MGUS/SMM patients were examined concerning 14q32 chromosomal trans locations by means of double color-FISH analysis. 56% of the cases carried 14q32 translocations, in which two thirds were between 14q32(IgH) and 11q13(CCND1) loci with concomitant nuclear expression of CyclinD1. 3.Identification of the distinct developmental pathways of multiple myeloma : Quantitative RT-PCR assay was established for CCND1, FGFR3, MUM1, c-MAF, MAFB and c-MYC genes, and applied for the study of 19 cell lines and 30 myeloma samples. It led to the identification of at least three distinct developmental pathways of multiple myeloma, which originated from altered expression of CCND1, FGFR3 and c-MAF/MAFB genes.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 1999 -2001 
    Author : WAKITA Atsushi; KOMATSU Hirokazu; IIDA Shinsuke; UEDA Ryuzo
     
    We investigate 42 members out degree in a family with hereditary essential thrombocythemia. Ten members had already died, and the causes of the deaths are 2 of old age, one brain hemorrage and one cerebral infarction. Eighteen members who alive were received blood examination, essential thrombocythemia was diagnosed for 9 patients. In the essential thrombocythemia patients, the age was 7 to 64 years old. The oldest patients had complication brain hemorrage and he died of second hemorragic attack. On deaths, his bone marrow showed myelofibrosis and platelet count was lower than normal. There was no patients with trombotic or hemorragic complications. Other symptoms resulting from platelet increment were, one patient had headache and one had dizziness, they were not serious. Platelet function test showed decreased ADP aggregation and epinephrine aggregation in the patients, they were normal in the healthy members. Platelet adhesion test was almost normal. Oral mucous sample was harvested from 7 female patients, which were examined clonality analysis using polymorphism of HUMARA gene. There was no evidence of clonal shift in the all seven patients. Sereum thrombopoietin level almost normal in the patients, and completely normal in the healthy members. Analysis of c-Mpl mutaion was daone in two patients. Kown mutations were not detected in our patients.
  • 形質細胞性腫瘍の発生に関与する癌遺伝子の単離同定とその機能解析
    Date (from‐to) : 1999 -2000
  • 難治性リンパ系腫瘍におけるヒストン脱アセチル化酵素阻害剤に対する耐性化機構の解明
    名古屋市立大学：
    Author : 飯田真介; 李政樹
  • リンパ系腫瘍におけるMUM1/IRF4の転写標的遺伝子の同定と治療標的分子の探索

Social Contribution

  • 独立行政法人医薬品・医療機器総合機構(Pmda)外部専門委員
    Date (from-to) : 2012/04-2013/03
    Sponser, Organizer, Publisher  : 行政
    名古屋市立大学桜山キャンパス 重篤な副作用症例に関する評価
  • 独立行政法人医薬品・医療機器総合機構(Pmda)外部専門委員
    Date (from-to) : 2012/12/27-2012/12/27
    Sponser, Organizer, Publisher  : 行政
    医薬品・医療機器総合機構 新薬承認審査前のPmda内での審査報告書の審議
  • 公益社団法人日本看護協会 セミナー講師
    Date (from-to) : 2012/11/16-2012/11/16
    Sponser, Organizer, Publisher  : 地域団体・NPO
    日本看護協会 神戸研修センター がん専門看護師養成セミナーの講師
  • 厚生労働省医薬食品局「必要性の高い未承認薬・適応外薬検討会議」委員
    Date (from-to) : 2012/06/18-2012/11/05
    Sponser, Organizer, Publisher  : 行政
    医薬品・医療機器総合機構 抗がんワーキンググループ委員として公知承認等の適切性の審議に参加（2012年6月18日、8月21日、11月5日）
  • 患者会 セミナー講師
    Date (from-to) : 2012/07/08-2012/07/08
    Sponser, Organizer, Publisher  : 地域団体・NPO
    京都テルサ 日本骨髄腫患者の会主催のセミナー講師を務めた。

Other link

researchmap


Copyright © MEDIA FUSION Co.,Ltd. All rights reserved.