Research Topic: Synthetic Cell Biology

Our research focuses on synthetic cell biology to dissect intricate signaling networks. In particular, we investigate positive-feedback mechanisms underlying the initiation of neutrophil chemotaxis (known as a symmetry breaking process), as well as spatio-temporally compartmentalized Ras signaling. In parallel, our lab also tries to understand how cell morphology affects biochemical functions in cells. Ultimately, we will generate completely orthogonal nano-machinery in cells that can achieve existing, and even novel, cellular functions.

Figure 3: Tools to manipulate protein activity at specific subcellular compartments
(a) A principle diagram for inducible recruitment of signaling molecules (green circles). c, cytoplasm, o, organelle.  (b) Confocal fluorescence images of HeLa cells showing rapid translocation of cytoplasmic proteins to specific organelles upon 5 mM iRap addition for 5 minutes. Scale bar indicates 20 µm.

Selected Publications

Miyamoto T., DeRose R., Suarez A., Ueno T., Chen M., Sun T.-p., Wolfgang MJ., Mukherjee C., Meyers D., and Inoue T. "Generation of Intracellular Logic Gates with Two Orthogonal Chemically Inducible Systems." Nature Chemical Biology (Accepted 2012).

Ueno T., Falkenburger B.H., Pohlmeyer C., and Inoue T. “Triggering Actin Comets Versus Membrane Ruffles: Distinctive Effects of Phosphoinositides on Actin Reorganization” ScienceSignaling 4(203), ra87 (2011) (Cover Article).

Umeda N., Ueno T., Pohlmeyer C., Nagano T. and Inoue T. “A photocleavable rapamycin conjugate for spatiotemporal control of small GTPase activity” Journal of American Chemical Society 133(1), 12-14 (2011)
Note: “Scientist 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. and Inoue T. “Organelle-Specific, Rapid Induction of Molecular Activities and Membrane Tethering” Nature Methods 7, 206-208 (2010)
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., and Devreotes P.N. “A phosphorylation-dependent intramolecular interaction regulates the membrane association and activity of the tumor suppressor PTEN” Proc. Natl. Acad. Sci. U S A.106(2):480-5 (2009)

Inoue T. and Meyer T. “Synthetic activation of endogenous PI3K and Rac identifies an AND-gate switch for cell polarization and migration”  PLoS ONE3(8), e3068 (2008)

Fivaz M., Bandara S., Inoue T. and Meyer T. "Robust neuronal symmetry breaking by Ras-triggered local positive feedback" Current Biology 18, 44-50 (2008)

Suh BC*, Inoue T*, Meyer T, and Hille B. “Rapid chemically-induced changes of PtdIns(4,5)P2 gate KCNQ ion channels” Science 314, 1454-1457 (2006) (*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))

Heo WD, Inoue T, Park WS, Kim ML, Park BO, Wandless TJ, and 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)

Inoue T, Heo WD, Grimley JS, Wandless TJ, and Meyer T. “Inducible translocation strategies to rapidly activate and inhibit small GTPase signaling pathways” Nature Methods 2, 415-418  (2005)

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)
Note: “Cover art”

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