Search for a novel biological regulatory system based on low temperature biology

• Project/Area Number: 26670110
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Gunma University
• Principal Investigator: OHNISHI HIROSHI 群馬大学, 大学院保健学研究科, 教授 (70334125)
• Co-Investigator(Renkei-kenkyūsha): HASHIMOTO Miho 学術振興会, 特別研究員 (90381087) ; Kusakari Shinya 東京医科大学, 医学部, 助教 (10510901) ; KODERA Yoshio 北里大学, 理学部, 准教授 (60265733) ; KANEKO Yoriaki 群馬大学, 大学院医学系研究科, 講師 (00334095) ; KITAMURA Tadahiro 群馬大学, 生体調節研究所, 教授 (20447262) ; KOBAYASHI Masaki 群馬大学, 生体調節研究所, 助教 (80373041)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: チロシンリン酸化 / 低体温 / ストレス / 生体保護 / Cl-チャネル / 分子シャペロン

Outline of Final Research Achievements

The function and molecular mechanism of low temperature-induced tyrosine phosphorylation of a membrane protein SIRPα were investigated. As a result of examinations, there was a possibility that the low temperature-induced SIRPα signal might be related to suppressive action of hypothermia on memory formation and/or maintenance. In addition, possibilities that the SIRPα signal might enhance the susceptibility of cultured neurons to low temperature stress, and that it might contribute to the suppression of the LPS-induced systemic inflammatory response, were considered. In addition, possible molecular interaction between SIRPα and molecular chaperons, and the importance of ligand-biding to the extracellular region of SIRPα in cold-induced SIRPα phosphorylation, were indicated.

Research Products

• [Journal Article] Anti-SIRPα antibodies as a potential new tool for cancer immunotherapy. (2017)
  • Author(s): Yanagita T, Murata Y, Tanaka D, Motegi S, Arai E, Daniwijaya EW, Hazama D, Washio K, Saito Y, Kotani T, Ohnishi H, Oldenborg PA, Verjan Garcia N, Miyasaka M, Ishikawa O, Kanai Y, Komori T, Matozaki T.
  • Journal Title: JCI Insight Volume: 2 Issue: 1
  • DOI: 10.1172/jci.insight.89140
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Relationship between tumor-associated macrophage subsets and CD47 expression in squamous cell carcinoma of the head and neck in the tumor microenvironment. (2016)
  • Author(s): Sakakura K, Takahashi H, Kaira K, Toyoda M, Murata T, Ohnishi H, Oyama T, Chikamatsu K.
  • Journal Title: Lab Invest Volume: 96 Issue: 9 Pages: 994-1003
  • DOI: 10.1038/labinvest.2016.70
  • Peer Reviewed
• [Journal Article] Shp2 in forebrain neurons regulates synaptic plasticity, locomotion, and memory formation in mice (2015)
  • Author(s): Kusakari S, Saitow F, Ago Y, Shibasaki K, Sato-Hashimoto, M., Matsuzaki, Y., Kotani T, Murata Y, Hirai H, Matsuda T, Suzuki H, Matozaki T, Ohnishi H
  • Journal Title: Mol. Cell. Biol. Volume: 35 Issue: 9 Pages: 1557-1572
  • DOI: 10.1128/mcb.01339-14
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Adult mice expressing a Braf Q241R mutation on an ICR/CD-1 background exhibit a cardio-facio-cutaneous syndrome phenotype. (2015)
  • Author(s): Moriya M, Inoue S, Miyagawa-Tomita S, Nakashima Y, Oba D, Niihori T, Hashi M, Ohnishi H, Kure S, Matsubara Y, Aoki Y.
  • Journal Title: Hum Mol Genet. Volume: 24 Issue: 25 Pages: 7349-7360
  • DOI: 10.1093/hmg/ddv435
  • Peer Reviewed
• [Journal Article] Pathogenesis of multiple lentigines in LEOPARD syndrome with PTPN11 gene mutation (2015)
  • Author(s): Motegi S, Yokoyama Y, Ogino S, Yamada K, Uchiyama A, Takeuchi Y, Ohnishi H, Ishikawa O
  • Journal Title: Acta Derm Venereol Volume: 95 Issue: 8 Pages: 978-984
  • DOI: 10.2340/00015555-2123
  • Peer Reviewed
• [Journal Article] ミクログリアを制御する細胞間相互作用シグナル (2015)
  • Author(s): 橋本美穂、大西浩史
  • Journal Title: Clinical Neuroscience Volume: 33 Pages: 1350-1353
• [Journal Article] The CD47-SIRPα signalling system : its physiological roles and therapeutic application (2014)
  • Author(s): Murata Y, Kotani T, Ohnishi H, Matozaki T
  • Journal Title: J Biochem Volume: 155 Issue: 6 Pages: 335-344
  • DOI: 10.1093/jb/mvu017
  • NAID: 40020088978
  • Peer Reviewed
• [Journal Article] Comprehensive behavioral analysis of cluster of differentiation 47 knockout mice (2014)
  • Author(s): Koshimizu H, Takao K, Matozaki T, Ohnishi H, Miyakawa T
  • Journal Title: PLoSOne Volume: 9 Issue: 2 Pages: e89584-e89584
  • DOI: 10.1371/journal.pone.0089584
  • Peer Reviewed / Open Access
• [Journal Article] Autoimmune animal models in the analysis of the CD47-SIRPα signaling pathway (2014)
  • Author(s): Murata Y, Saito Y, Kaneko T, Kotani T, Kaneko Y, Ohnishi H, Matozaki T
  • Journal Title: Methods Volume: 65 Issue: 2 Pages: 254-9
  • DOI: 10.1016/j.ymeth.2013.09.016
  • Peer Reviewed
• [Presentation] 細胞間接触シグナルによる脳内グリア恒常性制御 (2017)
  • Author(s): 大西浩史
  • Organizer: 第６回Multidisciplinary meeting on atherosclerosis
  • Place of Presentation: 仙台
  • Invited
• [Presentation] Analysis of a direct cell-cell communication signal that regulates glial acrivation in the brain (2016)
  • Author(s): Tomomi Nozu, Miho Hashimoto, Ruwaida Elhanbaly, Tatsuya Ishikawa, Ayaka Hirose, Waka Shimizu, Takashi Matozaki, Yugo Fukazawa, Hiroshi Ohnishi
  • Organizer: 12th International Conference on Protein Phosphatase
  • Place of Presentation: 近畿大学
  • Year and Date: 2016-10-27
  • Int'l Joint Research
• [Presentation] SIRPα欠損マウスにおけるクプリゾン感受性の亢進 (2016)
  • Author(s): 野津智美、橋本美穂,Ruwaida Elhanbaly, 石川達也、齊藤泰之、小谷武徳、村田陽二、深澤有吾、的崎尚、大西浩史
  • Organizer: 第63回北関東医学会総会
  • Place of Presentation: 群馬大学
  • Year and Date: 2016-09-29
• [Presentation] SIRPα欠損マウスはLPS投与によって誘導される低体温症が重症化する (2016)
  • Author(s): 橋本美穂、野津智美、浦野江里子、齊藤泰之、小谷武徳、村田陽二、的崎尚、大西浩史
  • Organizer: 第38回日本生物学的精神医学会・第59回日本神経化学会大会 合同年会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2016-09-08
• [Presentation] 白質におけるミクログリア恒常性制御 (2016)
  • Author(s): 野津智美、橋本美穂,Ruwaida Elhanbaly, 石川達也、齊藤泰之、小谷武徳、村田陽二、的崎尚、深澤有吾、大西浩史
  • Organizer: 第38回日本生物学的精神医学会・第59回日本神経化学会大会 合同年会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2016-09-08
• [Presentation] ミクログリアにおけるSIRPαの役割 (2015)
  • Author(s): 橋本美穂、野津智美，浦野江里子 齊藤泰之，小谷武徳，村田陽二 的崎 尚
  • Organizer: 第62回北関東医学会総会
  • Place of Presentation: 群馬大学 刀城会館（前橋）
  • Year and Date: 2015-10-01
• [Presentation] Cell-cell interactions via CD47-SIRPα signal regulate microglial activation (2015)
  • Author(s): Sato-Hashimoto M, Nozu T, Urano E, Saito Y, Kotani T, Murata Y, Matozaki T, Ohnishi H
  • Organizer: 第58回日本神経化学会大会
  • Place of Presentation: 大宮ソニックシティ（大宮）
  • Year and Date: 2015-09-12
• [Presentation] Behavioral phenotypes of neuron-specific Shp2 conditional knockout mice (2015)
  • Author(s): Ohnishi H, Kusakari S, Hashimoto M, Ishikawa S, Urano E, Kotani T, Murata Y, Matozaki T
  • Organizer: 第58回日本神経化学会大会
  • Place of Presentation: 大宮ソニックシティ（大宮）
  • Year and Date: 2015-09-12
• [Presentation] Analysis of cell-cell interaction signal that regulates microglial homeostasis (2015)
  • Author(s): Sato-Hashimoto M, Nozu T, Urano E, Saito Y, Kotani T, Murata Y, Matozaki T, Ohnishi H
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸コンベンションセンター（ポートアイランド）(神戸)
  • Year and Date: 2015-07-28
• [Presentation] Behavioral analysis of forebrain neuron-specific Shp2 conditional knockout mice (2015)
  • Author(s): Ohnishi H, Kusakari S, Hashimoto M, Ishikawa S, Urano E, Kotani T, Murata Y, Matozaki T
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸コンベンションセンター（ポートアイランド）(神戸)
  • Year and Date: 2015-07-28
• [Presentation] Essential role of SIRPα on dendritic cells in organization and homeostasis of the spleen (2014)
  • Author(s): Washio K, Kotani T, Respatika D, Murata Y, Saito Y, Okazawa H, Ohnishi H, Fukunaga A, Nishigori C, Matozaki T
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Immunological analysis of autoimmune nephritis observed in DC-specific Shp1 conditional knockout mice (2014)
  • Author(s): Watanabe M, Kaneko Y, Hiromura K, Ohishi Y, Kinoshita M, Ohnishi H, Matozaki T, Nojima Y
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Functional analysis of protein tyrosine phosphatase Shp2 in post-mitotic neurons (2014)
  • Author(s): Kusakari S, Saitow F, Hashimoato M, Matsuzaki Y, Kotani T, Murata Y, Hirai H, Suzuki H, Matozaki T, Ohnishi H
  • Organizer: 11th International Conference on Protein Phosphatase Protein Phosphatases in Health and Diseases
  • Place of Presentation: 東北大学医学部 艮陵会館（宮城県仙台市）
  • Year and Date: 2014-11-12 – 2014-11-14
• [Presentation] Regulation of microglial homeostasis through cell-cell interaction signal (2014)
  • Author(s): Sato-Hashimoto M, Hayashi Y, Kusakari S, Kotani T, Murata Y, Matozaki T, Ohnishi H
  • Organizer: Neuroscience 2014 第３７回日本神経科学大会 The 37th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: パシフィコ横浜（神奈川県）
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Functional Analysis of protein tyrosine phosphatase Shp2 in the adult forebrain neurons (2014)
  • Author(s): Ohnishi H, Kusakari S, Saitow F, Hashimoto M, Matsuzaki Y, Kotani T, Murata Y, Hirai H, Suzuki H, Matozaki T
  • Organizer: Neuroscience 2014 第３７回日本神経科学大会 The 37th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: パシフィコ横浜（神奈川県）
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] 腸上皮の恒常性維持におけるチロシンホスファターゼShp2の役割 Role of the protein tyrosine phosphatase Shp2 in maintaining homeostasis of the intestinal epithelium (2014)
  • Author(s): 小谷武徳、山下博成、村田陽二、岡澤秀樹、大西浩史、具英成、的崎尚
  • Organizer: 第66回日本細胞生物学会大会
  • Place of Presentation: 奈良県新公会堂・東大寺総合文化センター・奈良国立博物館
  • Year and Date: 2014-06-11 – 2014-06-13
• [Presentation] 樹状細胞とSLE：樹状細胞特異的SHP-1欠損マウスの解析 (2014)
  • Author(s): 廣村桂樹、渡辺光治、大石裕子、金子和光、斎藤泰之、金子哲也、高岸憲二、 大西浩史、的崎 尚、野島美久
  • Organizer: 第58回 日本リウマチ学会総会・学術集会
  • Place of Presentation: グランドプリンスホテル新高輪（東京）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Book] 脳内環境 ー 維持機構と破綻がもたらす疾患研究 (2014)
  • Author(s): （編集）高橋良輔、漆谷真、山中宏二、樋口真人 （著者）大西浩史 他
  • Total Pages: 228
  • Publisher: 株式会社 メディカルドゥ
• [Remarks] 群馬大学_大西研究室
  • URL: http://biosignal.dept.med.gunma-u.ac.jp/
• [Remarks] 群馬大学 大西研究室ホームページ
  • URL: http://biosignal.dept.med.gunma-u.ac.jp/