Development of tools and activity measurement methods for artificial manipulation of Notch signaling pathway

• Project/Area Number: 25670020
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Chiba University
• Principal Investigator: ITOH MOTOYUKI 千葉大学, 大学院薬学研究院, 教授 (20377906)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: Notch / シグナル伝達 / 固相化

Outline of Final Research Achievements

Notch signaling plays important roles in various tissue development, and its manupiration is useful for artificially inducing the differentiation from pluripotent cells into target cells. In this study, human D114 and JAG1 ligand-immobilized beads were prepared and we demonstrated that they showed T cell-inducing activity from hematopoietic progenitor cells. Further, we succeeded in developing a Dll4 ligand protein with superior activity to wild type by introducing a point mutation.

Research Products

• [Journal Article] Identification of domains for efficient Notch signaling activity in immobilized Notch ligand proteins. (2016)
  • Author(s): Liu L, Wada H, Matsubara N, Hozumi K and Itoh M.
  • Journal Title: J Cell Biochem Volume: 118 Issue: 4 Pages: 785-796
  • DOI: 10.1002/jcb.25744
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Identification of domains for efficient Notch signaling activity in immobilized Notch ligand proteins Notch meeting: Fine tuning of Notch signaling activity: its importance and mechanisms (2016)
  • Author(s): Ledi Liu1, Hiroe Wada, Natsuki Matsubara, Kensuke Izumoto, Katsuto Hozumi, Motoyuki Itoh
  • Organizer: Notch meeting
  • Place of Presentation: Lecture Hall in National Institute of Genetics (Mishima, Japan)
  • Year and Date: 2016-10-05
• [Presentation] Identification of the critical region of Notch ligand for stimulating signal using immobilized proteins (2015)
  • Author(s): Ledi Liu, Hiroe Wada, Natsuki Matsubara, Kensuke Izumoto, Katsuto Hozumi, Motoyuki Itoh
  • Organizer: 第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] Immobilized Notch ligand proteins activate Notch signaling through MNNL-EGF repeat 3 region. (2014)
  • Author(s): Ledi Liu, Hiroe Wada, Natsuki Matsubara, Kensuke Izumoto, Motoyuki Itoh
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Remarks] 千葉大学薬学研究院生化学研究室
  • URL: http://www.p.chiba-u.jp/lab/seika/index.html
• [Remarks] 千葉大学薬学研究院生化学研究室ホームページ
  • URL: http://www.p.chiba-u.ac.jp/lab/seika/index.html
• [Remarks] 生化学研究室ホームページ
  • URL: http://www.p.chiba-u.ac.jp/lab/seika/index.html