Our lab is focused on developing novel chemical perturbation techniques and understanding the molecular mechanisms underlying cell migration by applying these techniques. With these techniques, we can inducibly manipulate the activity of various signaling molecules involved in cell migration, such as small GTPases and membrane lipids in intact living cells with a second timescale. This method is extremely powerful, as it has been successfully applied to several different biological systems and has resolved two long-standing mysteries in signal transduction: the regulatory mechanisms governing potassium ion channels (conducted with Bertil Hille’s group at University of Washington), and the membrane targeting mechanisms of small GTPases. We will craft a program of study that will quantitatively and spatiotemporally define migration in chemotactic cells. We hypothesize that there is only a handful of critical molecular steps regulating a symmetry breaking event that initiates migration. If true, this model would usher in a new paradigm for cellular migration. With a strong interdisciplinary background, we will personify the kind of work for which our lab stands: innovative research that drives science forward.

Publications:

1. Suh B.C. *, Inoue T. *, Meyer T. and Hille B. Science 314, 1454-1457 (2006) “Rapid chemically-induced changes of PtdIns(4,5)P2 gate KCNQ ion channels” (*Contributed Equally) Note: “Perspectives” (Science 314, 1402-1403 (2006)), “Editor’s Choice” (Science STKE 364, tw410 (2006)), “Spotlight” (ACS Chem. Biol. 1, 608 (2006)), “Research Highlights” (Nature Methods 4, 7 (2007)) and “Review” (invited by Nature Chem. Biol.).

2. Heo W.D., Inoue T., Park W.S., Kim M.L., Park B.O., Wandless T.J. and Meyer T. Science 314, 1458-1461 (2006) “PI(3,4,5)P3 and PI(4,5)P2 lipids target Ras, Rho, Arf and Rab GTPases to the plasma membrane” 3. Inoue T. *, Heo W.D., Grimley J.S., Wandless T.J., and Meyer T. (2005) Nature Methods 2, 415-418. “Inducible translocation strategies to rapidly activate and inhibit small GTPase signaling pathways” (*Corresponding Author)

4. Inoue T. *, Kikuchi K., Hirose K., Iino M., and Nagano T. (2003) Chem. Biol. 10, 503-509. “Spatiotemporal Laser Inactivation of Inositol 1,4,5-Trisphosphate Receptors Using Synthetic Small-molecule Probes” (*Cover Article)

5. Inoue T., Kikuchi K., Hirose K., Iino M., and Nagano T. (2001) Chem. Biol. 8, 9-15. “Small molecule-based laser inactivation of inositol 1,4,5-trisphosphate receptor”

6. Inoue T., Kikuchi K., Hirose K., Iino M., and Nagano T. (1999) Bioorg. Med. Chem. Lett. 9, 1697-1702. “Synthesis and evaluation of 1-position-modified inositol 1,4,5-trisphosphate analogs”