Analysis of filamin's role in platelet production

• Project/Area Number: 19591146
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Kurume University
• Principal Investigator: OKAMURA Takashi (2008) Kurume University, 医学部, 教授 (30136436); 金地 泰典 (2007) Kurume University, 医学部, 助教 (40363428)
• Co-Investigator(Kenkyū-buntansha): OKAMURA Takashi 久留米大学, 医学部, 教授 (30136436)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2007: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 移植再生医療 / 血小板 / 血小板産生 / 巨大血小板 / 細胞骨格 / フィラミン / ES細胞

Research Abstract

GPIbαプロモーター下に緑色蛍光蛋白質GFPを発現させさらにその3'非翻訳領域に細胞骨格蛋白質フィラミンAの発現を特異的に抑制するmicro RNA配列を挿入する事で血小板特異的にフィラミンをノックダウンした巨核球、血小板をES細胞から得る事ができた。GFPの発現とフィラミンの発現は逆相関を認めたが、GFPの発現が弱くさらに高発現株をスクリーニング中である。同様のコンストラクトを用いてトランスジェニックマウスを作成中である。

Research Products

• [Journal Article] Characterization of the light chain-restricted clonal B cells in peripheral blood of HCV-positive patients. (2009)
  • Author(s): Ohtsubo K, Sata M, Kawaguchi T, Morishige S, Takata Y, Oku E, Imamura R, Seki R, Hashiguchi M, Osaki K, Yakushiji K, Kanaji T, Yoshimoto K, Ueno T, Okamura T.
  • Journal Title: Int J Hematol. 89 Pages: 452-9
  • NAID: 10025161209
  • Peer Reviewed
• [Journal Article] Identification of four novel mutations in F5 associated with congenital factor V deficiency. (2009)
  • Author(s): Kanaji S, Kanaji T, Honda M, Nakazato S, Wakayama K, Tabata Y, Shibata S, Gondo H, Nakamura I, Node K, Miura M, Miyahara M, Okamura T, Nagumo F, Ohta S, Izuhara K.
  • Journal Title: Int J Hematol. 89 Pages: 71-5
  • NAID: 10025159727
  • Peer Reviewed
• [Journal Article] Identification of four novel mutations in F5 associated with congenital factor V deficiency. (2009)
  • Author(s): Kanaji S
  • Journal Title: Int J Hematol 89 Pages: 71-75
  • Peer Reviewed
• [Journal Article] Metalloproteinase regulation improves in vitro generation of efficacious platelets from mouse embryonic stem cells. (2008)
  • Author(s): Nishikii H, Eto K, Tamura N, Hattori K, Heissig B, Kanaji T, Sawaguchi A, Goto S, Ware J, Nakauchi H.
  • Journal Title: J Exp Med. 205 Pages: 1917-27
• [Journal Article] Periostin and bone marrow fibrosis. (2008)
  • Author(s): Oku E, Kanaji T, Takata Y, Oshima K, Seki R, Morishige S, Imamura R, Ohtsubo K, Hashiguchi M, Osaki K, Yakushiji K, Yoshimoto K, Ogata H, Hamada H, Izuhara K, Sata M, Okamura T.
  • Journal Title: Int J Hematol. 88 Pages: 57-63
  • NAID: 10025159122
  • Peer Reviewed
• [Journal Article] In vivo relevance for platelet glycoprotein Ib. residue Tyr276 in thrombus formation. (2008)
  • Author(s): Guerrero JA, Shafirstein G, Russell S, Varughese KI, Kanaji T, Liu J, Gartner TK, Baumler W, Jarvis GE, Ware J.
  • Journal Title: J Thromb Haemost. 6 Pages: 684-91
  • Peer Reviewed
• [Journal Article] Lower factor XII activity is a risk marker rather than a risk factor for cardiovascular disease: a rebuttal. (2008)
  • Author(s): Kanaji T.
  • Journal Title: J Thromb Haemost. 6 Pages: 1053-4
• [Journal Article] Characterization of a patient with atypical amegakaryocytic thrombocytopenia. (2008)
  • Author(s): Kanaji S, Kanaji T, Migita M, Kunishima S, Kunicki TJ, Okamura T, Izuhara K.
  • Journal Title: Eur J Haematol. 80 Pages: 361-4
  • Peer Reviewed
• [Journal Article] Platelet dysfunction and a high bone mass phenotype in a murine model of platelet-type von Willebrand disease. (2008)
  • Author(s): Suva LJ, Hartman E, Dilley JD, Russell S, Akel NS, Skinner RA, Hogue WR, Budde U, Varughese KI, Kanaji T, Ware J.
  • Journal Title: Am J Pathol. 172 Pages: 430-9
  • Peer Reviewed
• [Journal Article] Periostin and bone marrow fibrosis. (2008)
  • Author(s): Oku E
  • Journal Title: Int J Hematol 88 Pages: 57-63
  • Peer Reviewed
• [Journal Article] Platelet dysfunction and a high bone mass phenotype in a murine model of platelet-type von Willebrand disease (2008)
  • Author(s): Suva LJ
  • Journal Title: Am J Pathol 172 Pages: 430-439
  • Peer Reviewed
• [Journal Article] Characterization of a patient with atypical amegakaryocytic thrombocytopenia (2008)
  • Author(s): Kanaji S
  • Journal Title: Eur J Haematol 80 Pages: 361-364
  • Peer Reviewed
• [Journal Article] In vivo relevance for platelet glycoprotein Ibalpha residue Tyr276 in thrombus formation (2008)
  • Author(s): Guerrero JA
  • Journal Title: J Thromb Haemost 6 Pages: 684-91
  • Peer Reviewed
• [Journal Article] Lower factor XII activity is a risk marker rather than a risk factor for cardiovascular disease:a rebuttal (2008)
  • Author(s): Kanaji T
  • Journal Title: J Thromb Haemost
  • Peer Reviewed
• [Presentation] Platelets having a W127X mutation in GPIX express sufficient residual amounts of the GPIba chain to support ristocetin-mediated agglutination and adhesion to VWF and collagen under conditions of flow. (2008)
  • Author(s): Kanaji T
  • Organizer: 50 th American Society of Hematology
  • Place of Presentation: San Francisco, CA U.S.A
  • Year and Date: 2008-12-06
• [Presentation] 初診時から30年後にType 2N/3と遺伝子診断できたVon Willebrand病姉妹例の解析 (2007)
  • Author(s): 金地 泰典
  • Organizer: 第30回日本血栓止血学会学術集会
  • Place of Presentation: 志摩
  • Year and Date: 2007-11-16
• [Presentation] 初診時から30年後にType 2N/3と遺伝子診断できた Von Willebrand 病姉妹例の解析 (2007)
  • Author(s): 金地 泰典, 緒方 秀章, 吉本 幸治, 関 律子, 高田 由香, 奥 英二郎, 森重 聡, 大坪 維範, 今村 理恵, 橋口 道俊, 大崎 浩一, 薬師寺 和昭, 岡村 孝
  • Organizer: 第30回日本血栓止血学会学術集会
  • Place of Presentation: 志摩
  • Year and Date: 2007-11-15
• [Presentation] 骨髄増殖性疾患(MPD)におけるJAK2V617F変異の頻度と病態の検討 (2007)
  • Author(s): 高田 由香, 金地 泰典, 緒方 秀章, 吉本 幸治, 薬師寺 和昭, 橋口 道俊, 大崎 浩一, 今村 理恵, 大坪 惟範, 奥 英二郎, 森重 聡, 関 律子, 南野 隆一, 岡村 孝
  • Organizer: 第69回日本血液学会総会、第49回日本臨床血液学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-11
• [Presentation] 無巨核球性血小板減少症患者におけるc-mplとGPVIの発現相関c-mplとGPVIの発現相関 (2007)
  • Author(s): 金地 泰典, 金地 佐千子, 右田昌宏, 国島 伸治, 出原 賢治, 岡村 孝
  • Organizer: 第69回日本血液学会総会、第49回日本臨床血液学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-11
• [Presentation] 無巨核性血小板減少症患者におけるc-mplおGPVIの発現相関 (2007)
  • Author(s): 金地 泰典
  • Organizer: 第69回日本血液学会総会、第49回日本臨床血液学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-11
• [Presentation] Platelet having a W127X mutation in GPIX express sufficient residual amounts of GPIbτ chain to support ristocetin-mediated agglutination and adhesion to VWF and collagen under condition of flow.
  • Author(s): Kanji T, Takata Y, Moroi M, Seki R, Oku E, Sano M, Nakazato S, Izuhara K, Sueoka E, Imamura Y, Okamura T.
  • Organizer: 50^<th> American Society of Hematology
  • Place of Presentation: San Francisoco
• [Book] Clinical role of protein S deficiency in Asian population.Tanaka K. Daivie EW (Eds). Recent advance in thrombosis and hematosis 2008 (2008)
  • Author(s): Hamasaki N, and Kanaji T.
  • Publisher: Springer