Myeloid cell dysfunction and the pathogenesis of ovarian hypertrophy.

• Project/Area Number: 15H04693
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Akita University
• Principal Investigator: Sasaki Junko 秋田大学, 医学(系)研究科(研究院), 准教授 (30333371)
• Co-Investigator(Renkei-kenkyūsha): NAKANISHI HIROKI 秋田大学, 大学生体情報研究センター, 助教 (10466740)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2015: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 細胞内シグナル伝達 / イノシトールリン脂質

Outline of Final Research Achievements

In this study we analyzed the relationship between aberrant lipid metabolism and the pathogenesis of ovarian hypertrophy using myeloid cell-specific phosphoinositide metabolizing enzymes-deficient mice (cDKO mice). We found that ovarian hypertrophy in cDKO mouse was induced by a high PIP3 level and Akt hyperactivation, and not only conventional myeloid cells but also uncharacterized cells contributed to the disease pathogenesis.

Research Products

• [Journal Article] TMEM55a localizes to macrophage phagosomes to downregulate phagocytosis (2018)
  • Author(s): Morioka Shin、Nigorikawa Kiyomi、Okada Eri、Tanaka Yoshimasa、Kasuu Yoshihiro、Yamada Miho、Kofuji Satoshi、Takasuga Shunsuke、Nakanishi Hiroki、Sasaki Takehiko、Hazeki Kaoru
  • Journal Title: Journal of Cell Science Volume: 131 Issue: 5 Pages: 213272-213272
  • DOI: 10.1242/jcs.213272
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] PTEN Regulates PI(3,4)P 2 Signaling Downstream of Class I PI3K (2017)
  • Author(s): Malek M、Kielkowska A、Chessa T、Anderson K E.、Barneda D、Pir P、Nakanishi H、Eguchi S、Koizumi A、Sasaki J、Juvin V、Kiselev VY.、Niewczas I、Gray A、Valayer A、Spensberger D、Imbert M、Felisbino S、Habuchi T、Beinke S、Cosulich S、Le Novere N、Sasaki T、Clark J、Hawkins PT.、Stephens LR.
  • Journal Title: Molecular Cell Volume: 68 Issue: 3 Pages: 566-580
  • DOI: 10.1016/j.molcel.2017.09.024
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The effect and possible clinical efficacy of in vivo inhibition of neutrophil extracellular traps by blockade of PI3K-gamma on the pathogenesis of microscopic polyangiitis (2017)
  • Author(s): Kimura Hirotaka、Matsuyama Yasushi、Araki Sachiko、Koizumi Atsushi、Kariya Yumi、Takasuga Shunsuke、Eguchi Satoshi、Nakanishi Hiroki、Sasaki Junko、Sasaki Takehiko
  • Journal Title: Modern Rheumatology Volume: 28 Issue: 3 Pages: 530-541
  • DOI: 10.1080/14397595.2017.1367116
  • Peer Reviewed / Open Access
• [Journal Article] Docosahexaenoic acid preserves visual function by maintaining correct disc morphology in retinal photoreceptor cells (2017)
  • Author(s): Shindou Hideo、Koso Hideto、Sasaki Junko、Nakanishi Hiroki、Sagara Hiroshi、Nakagawa Koh M.、Takahashi Yoshikazu、Hishikawa Daisuke、Iizuka-Hishikawa Yoshiko、Tokumasu Fuyuki、Noguchi Hiroshi、Watanabe Sumiko、Sasaki Takehiko、Shimizu Takao
  • Journal Title: Journal of Biological Chemistry Volume: 292 Issue: 29 Pages: 12054-12064
  • DOI: 10.1074/jbc.m117.790568
  • Peer Reviewed / Open Access
• [Journal Article] Lysophosphatidic acid acyltransferase 3 tunes the membrane status of germ cells by incorporating docosahexaenoic acid during spermatogenesis (2017)
  • Author(s): Iizuka-Hishikawa Yoshiko、Hishikawa Daisuke、Sasaki Junko、Takubo Keiyo、Goto Motohito、Nagata Katsuyuki、Nakanishi Hiroki、Shindou Hideo、Okamura Tadashi、Ito Chizuru、Toshimori Kiyotaka、Sasaki Takehiko、Shimizu Takao
  • Journal Title: Journal of Biological Chemistry Volume: 292 Issue: 29 Pages: 12065-12076
  • DOI: 10.1074/jbc.m117.791277
  • Peer Reviewed / Open Access
• [Journal Article] Vps34 regulates myofibril proteostasis to prevent hypertrophic cardiomyopathy. (2017)
  • Author(s): Kimura H, Eguchi S, Sasaki J, Kuba K, Nakanishi H, Takasuga S, Yamazaki M, Goto A, Watanabe H, Itoh H, Imai Y, Suzuki A, Mizushima N, Sasaki T
  • Journal Title: JCI Insight Volume: 2 Issue: 1 Pages: 89462-89478
  • DOI: 10.1172/jci.insight.89462
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Decreased 16:0/20:4-phosphatidylinositol level in the post-mortem prefrontal cortex of elderly patients with schizophrenia. (2017)
  • Author(s): Matsumoto J, Nakanishi H, Kunii Y, Sugiura Y, Yuki D, Wada A, Hino M, Niwa SI, Kondo T, Waki M, Hayasaka T, Masaki N, Akatsu H, Hashizume Y, Yamamoto S, Sato S, Sasaki T, Setou M, Yabe H.
  • Journal Title: Sci Rep. Volume: 7 Issue: 7 Pages: 45050-45050
  • DOI: 10.1038/srep45050
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Histone deacetylase inhibitors inhibit metastasis by restoring a tumor suppressive microRNA-150 in advanced cutaneous T-cell lymphoma. (2017)
  • Author(s): Abe F, Kitadate A, Ikeda S, Yamashita J, Nakanishi H, Takahashi N, Asaka C, Teshima K, Miyagaki T, Sugaya M, Tagawa H.
  • Journal Title: Oncotarget Volume: 8 Issue: 5 Pages: 7572-7585
  • DOI: 10.18632/oncotarget.13810
  • Peer Reviewed / Open Access
• [Journal Article] INPP4B is a PtdIns(3,4,5)P3 phosphatase that can act as a tumor suppressor. (2015)
  • Author(s): Kofuji S, Kimura H, Nakanishi H, Nanjo H, Takasuga S, Liu H, Eguchi S, Nakamura R, Itoh R, Ueno N, Asanuma K, Huang M, Koizumi A, Habuchi T, Yamazaki M, Suzuki A, Sasaki J, Sasaki T.
  • Journal Title: Cancer Discov. Volume: 5 Pages: 730-739
  • Peer Reviewed
• [Journal Article] Inositol Polyphosphate-4-Phosphatase Type I Negatively (2015)
  • Author(s): Nigorikawa, K., Hazeki, K., Sasaki, J., Omori, Y., Miyake, M., Morioka, S., Guo, Y., Sasaki, T., Hazeki, O
  • Journal Title: PLoS One Volume: 10 Issue: 11 Pages: 740-751
  • DOI: 10.1371/journal.pone.0142091
  • Peer Reviewed / Open Access
• [Journal Article] Loss of INPP4B causes a DNA repair defect through loss of BRCA1, ATM and ATR and can be targeted with PARP inhibitor treatment. (2015)
  • Author(s): Ip LR, Poulogiannis G, Viciano FC, Sasaki J, Kofuji S, Spanswick VJ, Hochhauser D, Hartley JA, Sasaki T, Gewinner CA.
  • Journal Title: Oncotarget Volume: 6 Issue: 12 Pages: 10548-10562
  • DOI: 10.18632/oncotarget.3307
  • Peer Reviewed
• [Presentation] INPP4B is a tumor suppressor in the context of PTEN insufficiency by modulating the levels of PI3K lipid products (2017)
  • Author(s): Takehiko Sasaki,Hiroki Nakanishi,Satoshi Eguchi,and Junko Sasaki
  • Organizer: International Symposium on Imaging Frontier 2017
  • Int'l Joint Research
• [Presentation] イノシトールリン脂質クオリティとシグナル伝達 (2017)
  • Author(s): 佐々木純子、中西広樹、刈屋佑美、江口賢史、佐々木雄彦
  • Organizer: 第69回日本細胞生物学会大会
• [Presentation] 性転換とリン脂質代謝 (2017)
  • Author(s): 佐々木純子
  • Organizer: リポクオリティ領域若手研究発表会
• [Presentation] A method for studying quality of phosphoinositides (2016)
  • Author(s): Takehiko Sasaki, Hiroki Nakanishi, Satoshi Eguchi, Masaki Ishikawa, Akira Suzuki, Junko Sasaki
  • Organizer: 第39回日本分子生物学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] ホスホイノシタイドの新しい解析方法 (2015)
  • Author(s): 中西広樹、江口賢史、石川将己、鈴木聡、佐々木純子、佐々木雄彦
  • Organizer: 第38回日本分子生物学会年会・第88回生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] 心肥大におけるホスホイノシタイド代謝酵素Vps34のタンパク質分解機構の役割 (2015)
  • Author(s): 木村洋貴、江口賢史、久場敬司、今井由美子、高須賀俊輔、伊藤玲悦、中村亮太郎、中西広樹、石川将己、佐々木純子、山崎正和、佐々木雄彦
  • Organizer: 第38回日本分子生物学会年会・第88回生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] イノシトールリン脂質研究の新しい方法論の提示 (2015)
  • Author(s): 中西広樹、小藤智史、江口賢史、中村亮太郎、石川将己、高須賀俊輔、佐々木純子、佐々木雄彦
  • Organizer: 第14回生命科学研究会
  • Place of Presentation: 三浦市民ホール
  • Year and Date: 2015-06-26
• [Book] 生体の科学 (2016)
  • Author(s): 中西広樹
  • Total Pages: 5
  • Publisher: 医学書院
• [Remarks]
  • URL: http://www.med.akita-u.ac.jp/~bisei/
• [Patent(Industrial Property Rights)] ホスホイノシタイド分離測定法の開発. (2017)
  • Inventor(s): 中西広樹 佐々木雄彦 佐々木純子 江口賢史 中西貴代
  • Industrial Property Rights Holder: 秋田大学 ALTe
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2017-051354
  • Filing Date: 2017-03-16
• [Patent(Industrial Property Rights)] 新規リン脂質およびその利用. (2016)
  • Inventor(s): 佐々木雄彦 中西広樹 石川将己 上野紀子 江口賢史 佐々木純子
  • Industrial Property Rights Holder: 秋田大学 ALTe
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-144177
  • Filing Date: 2016-07-22