• 研究室概要
• 主要研究テーマ
• スタッフ
• 主な研究実績
• 共同開発・研究
• 主な研究費取得状況

本寄附講座は令和５年３月３１日をもって終了いたしました。

成果報告書は こちらからご確認ください。

本講座は血栓塞栓症の発生病理と予防・治療を大きな目的としている。この課題へのアプローチとしてDAMPs, PAMPsの生物学を主軸としている。すなわち、・DAMPs, PAMPs の血栓塞栓発症への関与、・DAMPs, PAMPs 生成とそのシグナル伝達、代謝のダイナミズム、
そして、・それらの破綻の病態と制御法（予防と治療）、などを主たる目標として研究している。これらの研究の過程で見出したDAMPs, PAMPs とexosome の関係、トロンボモジュリンの役割などが直近の研究の焦点である。

研究室概要

連絡先

主要研究テーマ

スタッフ

特任教授

研究者総覧 リポジトリ

特任准教授

研究者総覧 リポジトリ

特任助教

研究者総覧 リポジトリ

特任助教

研究者総覧 リポジトリ

主な研究実績

丸山征郎

• Recombinant thrombomodulinの創薬化

原著論文

1. Maruyama I, Salem HH, Majerus PW.　 “Coagulation factor Va binds to human umbilical vein endothelial cells and accelerates protein C activation” J Clin Invest. 1984 Jul;74(1):224-30.
2. Salem HH, Maruyama I, Ishii H, Majerus PW.　 “Isolation and characterization of thrombomodulin from human placenta” J Biol Chem. 1984 Oct 10;259(19):12246-51.
3. Suzuki K, Kusumoto H, Deyashiki Y, Nishioka J, Maruyama I, Zushi M, Kawahara S, Honda G, Yamamoto S, Horiguchi S.　 “Structure and expression of human thrombomodulin, a thrombin receptor on endothelium acting as a cofactor for protein C activation” EMBO J. 1987 Jul;6(7):1891-7.
4. Maruyama I.　 “Thrombomodulin, an endothelial anticoagulant; its structure, function and expression” Jpn Circ J. 1992 Feb;56(2):187-91.
5. Abeyama K, Stern DM, Ito Y, Kawahara K, Yoshimoto Y, Tanaka M, Uchimura T, Ida N, Yamazaki Y, Yamada S, Yamamoto Y, Yamamoto H, Iino S, Taniguchi N, Maruyama I. “The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel antiinflammatory mechanism”. J Clin Invest. 2005 May;115(5):1267-74.
6. Yamada S, Yakabe K, Ishii J, Imaizumi H, Maruyama I.　 “New high mobility group box 1 assay system” 　 Clin Chim Acta. 2006 Oct;372(1-2):173-8.
7. Ito T, Kawahara K, Nakamura T, Yamada S, Nakamura T, Abeyama K, Hashiguchi T, Maruyama I. “High-mobility group box 1 protein promotes development of microvascular thrombosis in rats” J Thromb Haemost. 2007 Jan;5(1):109-16.
8. Ito T, Kawahara K, Okamoto K, Yamada S, Yasuda M, Imaizumi H, Nawa Y, Meng X, Shrestha B, Hashiguchi T, Maruyama I.：“Proteolytic cleavage of high mobility group box 1 protein by thrombin-thrombomodulin complexes” Arterioscler Thromb Vasc Biol. 2008 Oct;28(10):1825-30.
9. Nawa Y, Kawahara K, Tancharoen S, Meng X, Sameshima H, Ito T, Masuda Y, Imaizumi H, Hashiguchi T, Maruyama I. ：“Nucleophosmin may act as an alarmin: implications for severe sepsis” J Leukoc Biol. 2009 Sep;86(3):645-53.
10. Nakahara M, Ito T, Kawahara K, Yamamoto M, Nagasato T, Shrestha B, Yamada S, Miyauchi T, Higuchi K, Takenaka T, Yasuda T, Matsunaga A, Kakihana Y, Hashiguchi T, Kanmura Y, Maruyama I. ：“Recombinant thrombomodulin protects mice against histone-induced lethal thromboembolism” PLoS One. 2013 Sep 30;8(9):e75961.
11. Sadamura-Takenaka Y, Ito T, Noma S, Oyama Y, Yamada S, Kawahara K, Inoue H, Maruyama I.：“HMGB1 promotes the development of pulmonary arterial hypertension in rats” PLoS One. 2014 Jul 17;9(7):e102482.

伊藤隆史

＜論文＞

1. Ito T, Thachil J, Asakura H, Levy JH, Iba T.　Thrombomodulin in disseminated intravascular coagulation and other critical conditions-a multi-faceted anticoagulant protein with therapeutic potential.　Crit Care. (2019,23(1):280)
2. Ito T, Totoki T, Yokoyama Y, Yasuda T, Furubeppu H, Yamada S, Maruyama I, Kakihana Y.　Serum histone H3 levels and platelet counts are potential markers for coagulopathy with high risk of death in septic patients: a single-center observational study.　J Intensive Care. (2019,7:63)
3. Yokoyama Y, Ito T, Yasuda T, Furubeppu H, Kamikokuryo C, Yamada S, Maruyama I, Kakihana Y.　Circulating histone H3 levels in septic patients are associated with coagulopathy, multiple organ failure, and death: a single-center observational study.　Thromb J. (2019,17:1)
4. Yamakawa K, Yoshimura J, Ito T, Hayakawa M, Hamasaki T, Fujimi S.　External Validation of the Two Newly Proposed Criteria for Assessing Coagulopathy in Sepsis.　Thromb Haemost. (2019,119(2):203-212)
5. Yamamoto K, Ito T, Nagasato T, Shinnakasu A, Kurano M, Arimura A, Arimura H, Hashiguchi H, Deguchi T, Maruyama I, Nishio Y.　Effects of glycemic control and hypoglycemia on Thrombus formation assessed using automated microchip flow chamber system: an exploratory observational study.　Thromb J. (2019,17:17)
6. Shrestha B, Ito T, Kakuuchi M, Totoki T, Nagasato T, Yamamoto M, Maruyama I.　Recombinant Thrombomodulin Suppresses Histone-Induced Neutrophil Extracellular Trap Formation.　Front Immunol. (2019,10:2535)
7. Yashima N, Ito T, Kajiyama K, Maeda H, Kakihana Y, Maruyama I.　Leukocyte- derived extracellular DNA contributes to abnormal pressure elevation in the extracorporeal circulation circuit.　Sci Rep. (2020,10(1):474)
8. Ito T, Maruyama I, Shimazaki S, Yamamoto Y, Aikawa N, Hirayama A, Honda G, Saito H.　Effects of thrombomodulin alfa on hemostatic parameters in disseminated intravascular coagulation: Post hoc analysis of a phase 3 randomized controlled trial.　Res Pract Thromb Haemost. (2020,4(7):1141-1149)
9. Ito T, Shrestha B, Kakihana Y, Maruyama I.　Recombinant thrombomodulin alleviates oxidative stress without compromising host resistance to infection in rats infected with methicillin-resistant Staphylococcus aureus.　Sci Rep. (2020,10(1):17413)
10. Atari B, Ito T, Nagasato T, Ohnishi T, Hosokawa K, Yasuda T, Maruyama I, Kakihana Y　A modified microchip-based flow chamber system for evaluating thrombogenicity in patients with thrombocytopenia.　Thromb J. (2020,18:31)

大塚章太郎

＜論文＞

1. Otsuka S, Sakakima H, Sumizono M, Takada S, Terashi T, Yoshida Y. The neuroprotective effects of preconditioning exercise on brain damage and neurotrophic factors after focal brain ischemia in rats. Behav Brain Res. 15;303:9-18. 2016.
2. Kikuchi K, Setoyama K, Kawahara KI, Nagasato T, Terashi T, Ueda K, Nakanishi K, Otsuka S, Miura N, Sameshima H, Hosokawa K, Harada Y, Shrestha B, Yamamoto M, Morimoto-Yamashita Y, Kikuchi H, Kiyama R, Kamikokuryo C, Tancharoen S, Sakakima H, Morioka M, Tanaka E, Ito T, Maruyama I. Edaravone, a Synthetic Free Radical Scavenger, Enhances Alteplase-Mediated Thrombolysis. Oxid Med Cell Longev. 6873281. 2017.
3. Sumizono M, Sakakima H, Otsuka S, Terashi T, Nakanishi K, Ueda K, Takada S, Kikuchi K. The effect of exercise frequency on neuropathic pain and pain-related cellular reactions in the spinal cord and midbrain in a rat sciatic nerve injury model. J Pain Res. 11:281-291. 2018.
4. Kikuchi K, Setoyama K, Terashi T, Sumizono M, Tancharoen S, Otsuka S, Takada S, Nakanishi K, Ueda K, Sakakima H, Kawahara KI, Maruyama I, Hattori G, Morioka M, Tanaka E, Uchikado H. Application of a Novel Anti-Adhesive Membrane, E8002, in a Rat Laminectomy Model. Int J Mol Sci. 19(5). 2018.
5. Kikuchi K, Setoyama K, Tanaka E, Otsuka S, Terashi T, Nakanishi K, Takada S, Sakakima H, Ampawong S, Kawahara KI, Nagasato T, Hosokawa K, Harada Y, Yamamoto M, Kamikokuryo C, Kiyama R, Morioka M, Ito T, Maruyama I, Tancharoen S. Uric acid enhances alteplase-mediated thrombolysis as an antioxidant. Sci Rep. 8(1):15844. 2018.
6. Otsuka S, Sakakima H, Terashi T, Takada S, Nakanishi K, Kikuchi K. Preconditioning exercise reduces brain damage and neuronal apoptosis through enhanced endogenous 14-3-3γ after focal brain ischemia in rats. Brain Struct Funct. 224(2):727-738. 2019
7. Terashi T, Otsuka S, (double first), Takada S, Nakanishi K, Ueda K, Sumizono M, Kikuchi K, Sakakima H. Neuroprotective effects of different frequency preconditioning exercise on neuronal apoptosis after focal brain ischemia in rats. Neurol Res. 41(6):510-518. 2019
8. Takada S, Sakakima H, Matsuyama T, Otsuka S, Nakanishi K, Norimatsu K, Itashiki Y, Tani A, Kikuchi K. Disruption of Midkine gene reduces traumatic brain injury through the modulation of neuroinflammation. J Neuroinflammation. 29;17(1):40. 2020
9. Kikuchi K, Setoyama K, Takada S, Otsuka S, Nakanishi K, Norimatsu K, Tani A, Sakakima H, Kawahara KI, Hosokawa K, Kiyama R, Sumizono M, Tancharoen S, Maruyama I, Hattori G, Morioka M, Tanaka E, Uchikado H. E8002 Inhibits Peripheral Nerve Adhesion by Enhancing Fibrinolysis of l-Ascorbic Acid in a Rat Sciatic Nerve Model. Int J Mol Sci. 1;21(11):3972. 2020

髙田聖也

1. Otsuka S, Sakakima H, Terashi T, Takada S, Nakanishi K, Kikuchi K. Preconditioning exercise reduces brain damage and neuronal apoptosis through enhanced endogenous 14-3-3γ after focal brain ischemia in rats. Brain Struct Funct. 224(2):727-738. 2019
2. Sumizono M, Sakakima H, Otsuka S, Terashi T, Nakanishi K, Ueda K, Takada S, Kikuchi K. The effect of exercise frequency on neuropathic pain and pain-related cellular reactions in the spinal cord and midbrain in a rat sciatic nerve injury model. J Pain Res. 11:281-291. 2018.
3. Terashi T, Otsuka S, Takada S, Nakanishi K, Ueda K, Sumizono M, Kikuchi K, Sakakima H. Neuroprotective effects of different frequency preconditioning exercise on neuronal apoptosis after focal brain ischemia in rats. Neurol Res. 41(6):510-518. 2019
4. Kikuchi K, Setoyama K, Tanaka E, Otsuka S, Terashi T, Nakanishi K, Takada S, Sakakima H, Ampawong S, Kawahara KI, Nagasato T, Hosokawa K, Harada Y, Yamamoto M, Kamikokuryo C, Kiyama R, Morioka M, Ito T, Maruyama I, Tancharoen S. Uric acid enhances alteplase-mediated thrombolysis as an antioxidant. Sci Rep. 8(1):15844. 2018.
5. Kikuchi K, Setoyama K, Terashi T, Sumizono M, Tancharoen S, Otsuka S, Takada S, Nakanishi K, Ueda K, Sakakima H, Kawahara KI, Maruyama I, Hattori G, Morioka M, Tanaka E, Uchikado H. Application of a Novel Anti-Adhesive Membrane, E8002, in a Rat Laminectomy Model. Int J Mol Sci. 19(5). 2018.
6. Takada S, Sakakima H, Matsuyama T, Otsuka S, Nakanishi K, Norimatsu K, Itashiki Y, Tani A, Kikuchi K. Disruption of Midkine gene reduces traumatic brain injury through the modulation of neuroinflammation. J Neuroinflammation. 29;17(1):40. 2020
7. Otsuka S, Sakakima H, Sumizono M, Takada S, Terashi T, Yoshida Y. The neuroprotective effects of preconditioning exercise on brain damage and neurotrophic factors after focal brain ischemia in rats. Behav Brain Res. 15;303:9-18. 2016.
8. Kikuchi K, Setoyama K, Takada S, Otsuka S, Nakanishi K, Norimatsu K, Tani A, Sakakima H, Kawahara KI, Hosokawa K, Kiyama R, Sumizono M, Tancharoen S, Maruyama I, Hattori G, Morioka M, Tanaka E, Uchikado H. E8002 Inhibits Peripheral Nerve Adhesion by Enhancing Fibrinolysis of l-Ascorbic Acid in a Rat Sciatic Nerve Model. Int J Mol Sci. 1;21(11):3972. 2020
9. Sakakima H, Takada S, Norimatsu K, Otsuka S, Nakanishi K, Tani A. Diurnal Profiles of Locomotive and Household Activities Using an Accelerometer in Community-Dwelling Older Adults with Musculoskeletal Disorders: A Cross-Sectional Survey. Int J Environ Res Public Health. 17(15):5337.2020

主な特許等（出願中も含む）

共同開発・研究

• 糖鎖情報とmiRNA情報を組み合せた癌の細胞外小胞分析システム開発（アルプスアルパイン株式会社）
• 「人参養栄湯の老化抑制活性」に関する研究（株式会社ツムラ）
• 炎症・細胞障害関連蛋白質に対する抗体の作製及び評価（富山大学・ジーンテクノサイエンス）
• 遺伝子組換えトロンボモジュリンによるHMGB1分解促進効果の検証（旭化成ファーマ株式会社）
• 健常成人における血流下血栓形成ならびに好中球細胞下トラップ放出の解析（藤森工業株式会社）

主な研究費取得状況

丸山征郎

伊藤隆史

大塚 章太郎

髙田 聖也