Research Themes

• Development of Tiwan Habu-derived clot-busting agent
  Grant-in-Aid for Scientific Research (C)
  Teikyo Heisei University
  01 Apr. 2017 - 31 Mar. 2020
  The rattlesnake-derived metalloprotease-fragment which is referred to as the alfimeprase has strong fibrinolysis activity without hemorrhagic activity and does not show any adverse effect like the rtPA. The alfimeprase went in clinical development, but it was rapidly degraded by the alfa-2 macroglobulin in the blood vein, that resulted in no good efficacy. We have focused on the Taiwanese habu-derived toxin TM3(fibrinlysin) and developed the research on the clot-dissolving agent.
• Molecular mechanisms underlying pheromonogenesis linked to bombykol production
  Grant-in-Aid for Scientific Research (B)
  The Institute of Physical and Chemical Research
  2008 - 2010
  While it is well established that moth sex pheromones are de novo synthesized in the pheromone gland through modifications of fatty acid biosynthetic pathways, molecular mechanisms underlying sex pheromone production remained poorly understood. To address this, we have characterized some of the key molecules involved in the biosynthesis of the sex pheromone bombykol in the silkmoth, Bombyx mori. Characterization of these molecules has facilitated our understanding of the precise mechanisms underlying lepidopteran sex pheromone production.
• Establishment of RNAi methodology to Bombyx mori strain P50 and application for lepidopteran insects
  Grant-in-Aid for Scientific Research (C)
  The Institute of Physical and Chemical Research
  2007 - 2008
• Studies on molecular mechanisms underlying sex pheromone production in moths
  Grant-in-Aid for Scientific Research (B)
  The Institute of Physical and Chemical Research
  2005 - 2007
  The neurohormone PBAN (pheromone biosynthesis activating neuropeptide) regulates pheromone (bombykol) biosynthesis in the silkmoth, Bombyx marl, by binding to its cognate PBAN receptor, which is located in the pheromone gland (PG) cells of female moths. While extracellular Ca^<2+> had been shown to be essential for sex pheromone biosynthesis in all species studied to date, there had been no direct demonstration of this crucial event. To address this, we used fluorescent Ca^<2+> imaging techniques with isolated PGs to directly demonstrate that PBAN specifically triggers an influx of extracellular Ca^<2+>. Despite the efforts of numerous groups to understand the molecular mechanisms underlying bombykol production, little is known regarding how the external PBAN signal is converted to the calcium signal that drives bombykol production and release. To address this issue, we have taken advantage of the genome information in B. mori and characterized PG-specific genes[i.e. PG fatty acyl reductase (pgFAR), B. mori PG Z11/Δ10, 12 desaturase (Bmpgdesatl), PG acyl-CoA-binding protein (pgilCB1), midgut ACBP (mgACBI), and PBAN receptor (PBANR)] and successfully demonstrated their specific roles in bombykol biosynthesis in vivo by using an RNA interference-mediated loss-of-function approach.
• 昆虫の性フェロモンカスケードの分子メカニズムに関する研究
  Grant-in-Aid for Young Scientists (B)
  The Institute of Physical and Chemical Research
  2003 - 2004
• 害虫制御を目指したホルモンによる昆虫機能発現機構の包括的解析
  Grant-in-Aid for Exploratory Research
  The Institute of Physical and Chemical Research
  2002 - 2003