Takanari Inoue

Department Affiliation: Primary: Cell Biology; Secondary: Pharmacology and Molecular Sciences
Degree: Ph.D., University of Tokyo
Rank: Assistant Professor
Telephone Number: 443-287-7668
Fax Number: 410-614-8375
E-mail address: jctinoue@jhmi.edu
School of Medicine Address: 453 Rangos Bldg., 855 N. Wolfe Street, Baltimore, MD 21205

Synthetic cell biology, neutrophil chemotaxis, spatio-temporal signal compartmentalization, confocal fluorescence imaging, technology development.

Complexity in signaling networks is often derived from a limited set of molecules being co-opted for multiple tasks. Such multi-task molecules are best exemplified by Ras among others. Ras is a small GTPase that is active when bound to GTP and inactive when bound to GDP. Given its diverse function and its implication in cancer, it is no surprise that the Ras signaling pathway has been one of the most intensively studied signaling cascades in the last few decades. With the fruit of this research, we now know that Ras oversees diverse cellular functions such as cell proliferation, differentiation, migration, and T-cell activation. However, exactly how this simple binary switch can drive multiple cellular functions remains unresolved. Using a Ras signaling pathway as a model, we will challenge this fundamental question. We have recently developed a series of chemical-molecular tools that allow for inducible, quick-onset and specific perturbation of various signaling molecules. Using this novel technique in conjunction with conventional fluorescence imaging and biochemical analysis, we will delineate the spatio-temporal code encrypted in Ras’ intracellular dynamics.

Representative Publications:

Umeda, N., Ueno, T., Pohlmeyer, C., Nagano, Inoue, T. A photocleavable rapamycin conjugatefor spatiotemporal control of small GTPase activity. J. Amer. Chem. Society 133(1):12-14, 2011. Pub Med Reference
Note: "Scientists use light to move molecules within living cells" Science News article in ScienceDaily
Komatsu, T., Kukelyansky, I., McCaffery, J.M., Ueno, T., Varela, L.C., Inoue, T. Organelle-specific, rapid induction of molecular activities and membrane tethering. Nature Methods 7:206-208, 2010. Pub Med Reference
Note: "Hopkins researchers put proteins right where they want them" Breaking News article in Genetic Engineering and Biotechnology News
Rahdar, M., Inoue, T. , Meyer, T., Zhang, J., Vazquez, F., Devreotes, P.N. A phosphorylation-dependent intramolecular interaction regulates the membrane association and activity of the tumor suppressor PTEN. Proc. Natl. Acad. Sci. USA 106(2):480-5, 2009. Pub Med Reference
Inoue, T. and Meyer, T. Synthetic activation of endogenous PI3K and Rac identifies an AND-gate switch for cell polarization and migration. PLoS ONE 3(8):e3068, 2008. Pub Med Reference
Suh, B.C. *, Inoue, T. *, Meyer, T., Hille, B. Rapid chemically-induced changes of PtdIns(4,5)P₂ gate KCNQ ion channels. (*Contributed Equally) Science 314:1454-1457, 2006. Pub Med Reference
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.).
Heo, W.D., Inoue, T., Park, W.S., Kim, M.L., Park, B.O., Wandless, T.J., Meyer, T. PI(3,4,5)P₃ and PI(4,5)P₂ lipids target Ras, Rho, Arf and Rab GTPases to the plasma membrane. Science 314:1458-1461, 2006. Pub Med Reference
Inoue T., Heo, W.D., Grimley, J.S., Wandless, T.J., and Meyer, T. Inducible translocation strategies to rapidly activate and inhibit small GTPase signaling pathways. Nature Methods 2:415-418, 2005. Pub Med Reference
Inoue T., Kikuchi, K., Hirose, K., Iino, M., and Nagano, T. Spatiotemporal Laser Inactivation of Inositol 1,4,5-Trisphosphate Receptors Using Synthetic Small-molecule Probes. Chem. Biol. 10:503-509, 2003. (*Cover Article) Pub Med Reference