In addition to primary faculty, the department of biological chemistry is comprised of faculty from various departments throughout Johns Hopkins. Faculty who hold a secondary appointment in the department add yet another layer to the intellectual environment, scientifically and socially. Together, we continue to make significant contributions to our success. The inclusion of secondary faculty into our department further illustrates our commitment to diversity of scientific approach and the broad interest at Ho pkins in our departmental endeavors.
Room E5146Baltimore, MD 21205
Office Phone: 410-955-0105
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725 N. Wolfe St., 114 WBSBBaltimore, MD 21205
Office Phone: 410-614-9461
Lab Phone: 410-955-4699
Chemotaxis plays a key role in immune response, wound healing, angiogenesis, and embryogenesis as well as mediating cancer metastasis. Research in Dictyostelium discoideum has shown that chemoattractants are sensed by GPCRs and rapidly trigger a unique network of signaling pathways. Our strategy is to use the genetics of Dictyostelium to discover mechanisms by which cells sense chemical gradients and to apply this information to other eukaryotic cells such as human neutrophils and epithelial cells. We found that cell motility depends on spontaneous activation of the signal transduction network and that directional cues bias the threshold for activation. Numerous signal transduction events are activated or inactivated on each pseudopod. For example, activation of PI3K and inactivation of PTEN leads to a local accumulation of PIP3. Activation of protein kinases B requires both PIP3 and components of the Tor complex 2. By screening gene-tagged cell lines for mutants with phenotypes similar to those lacking the known signal transduction components, we are identifying novel genes involved in pathways.
Janetopoulos C, Jin T and Devreotes PN. 2001. Receptor mediated activation of heterotrimeric G-proteins in living cells. Science, 291, 2408-2411. PubMed ReferenceParent C. and Devreotes PN. 1999. A Cell's Sense of Direction. Science, 284, 765-770.PubMed ReferenceParent C, Blacklock B, Froelich W, Murphy D and Devreotes PN. 1998. G protein signaling events are activated at the leading edge of chemotactic cells. Cell, 95, 81-91.PubMed ReferencePitt GS, Milona N, Borleis J, Lin KC, Reed RR and Devreotes PN. 1992. Structurally distinct and stage-specific adenylyl cyclase genes play different roles in Dictyosteilum development. Cell 69, 305-315.PubMed ReferenceKlein PS, Sun TL. Saxe CL III, Kimmel AR, Johnson RL and Devreotes PN. 1988. A chemoattractant receptor controls development in Dictyostelium discoideum. Science 241, 1467-1472.PubMed ReferenceTomchik KJ and Devreotes PN. 1981. Cyclic AMP waves in Dictyostelium discoideum: A demonstration by isotope dilution fluorography. Science 212, 443-446.PubMed Reference
Ross 1012Baltimore, MD 21205
725 N. Wolfe St.Baltimore, MD 21205
Office Phone: (410) 955-0877
453 RangosBaltimore, MD 21205
Office Phone: 410-614-8375
Our research focuses on “synthetic cell biology” to dissect and reconstitute 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 dynamic information processing at various compartments in living cells. In parallel, our lab also tries to understand how cell morphology affects biochemical functions. Ultimately, we will generate completely orthogonal nano-machinery in artificial cells that can achieve existing, and even novel, cellular functions.
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Miyamoto T., Rho E, Sample V., Akano H., Magari M., Ueno T., Chen M., Tokumitsu H., Zhang J., and Inoue T. “Compartmentalized AMPK Signaling Illuminated by Genetically Encoded Molecular Sensors and Actuators” Cell Reports 11, 657-670 (2015)PubMed ReferenceLin B., Yin T., Wu Y.I., Inoue T. and Levchenko A. “Interplay between chemotaxis and contact inhibition of locomotion determines exploratory cell migration” Nature Communications 6, 6619 (2015)Note: Press release: “A digital field guide to cancer cells”PubMed ReferenceAdams P.J., Johny M.B., Dick I.E., Inoue T., and Yue D.T., “Apocalmodulin itself promotes ion channel opening and Ca2+ regulation” Cell 159 (3), 608-622 (2014)PubMed ReferenceRazavi S., Su S. and Inoue T. “Cellular Signaling Circuits Interfaced with Synthetic, Post-Translational, Negating Boolean Logic Devices” ACS Synthetic Biology 3 (9), 676-685 (2014)Note: “Introducing Authors” ACS Synthetic BiologyPubMed ReferenceOnuma H., Komatsu T., Arita M., Hanaoka K., Ueno T., Terai T., Nagano T., and Inoue T. "Rapidly rendering cells phagocytic through a cell-surface display technique and concurrent Rac activation" Science Signaling, 7, rs4, 1-7 (2014)Note: “Cover Story” Science Signaling, “Turning cells into garbage collector” Editor’s Choice in Science, Interviewed and broadcasted by FOX45 NEWS (https://drive.google.com/file/d/0B-wUSlcBaaEsSmpmQmhIblMzTXc/view?usp=sharing), Interview for “Thought Leaders” series by Medical-News, Press release: MOLECULAR “EAT NOW” SIGNAL MAKES CELLS DEVOUR DYING NEIGHBORS, “Training Cells to Devour Dying Neighbors” highlighted in NIGMS Biomedical Beat Blog, Highlighted in 5th Annual Henrietta Lacks Memorial Lecture, “Designer Immune Cells” highlighted in 2014 Research Highlights from Johns Hopkins Medicine (https://www.youtube.com/watch?v=Lb58GUNP5Qk)PubMed Reference
Suarez A, Ueno T, Huebner R, McCaffery JM, and Inoue T “Bin/Amphiphysin/Rvs (BAR) family members bend membranes in cells” Scientific Reports 4, (4693) 1-6 (2014)PubMed ReferenceKobayashi T, Kim S, Lin YC, Inoue T, and Dynlacht BD. “CP110-interacting proteins, Talpid3 and Cep290, play overlapping and distinct roles in cilia assembly” Journal of Cell Biology 204, 215-229 (2014)PubMed Reference Su S, Phua SC, DeRose R, Chiba S, Narita K, Kalugin PN, Katada T, Kontani K, Takeda . and Inoue T. “Genetically encoded calcium indicator illuminates calcium dynamics in cilia” Nature Methods 10, 1105-1107 (2013)Note: “Author File” Nature MethodsPubMed Reference
Thevathasa, JV, Tan E, Hui Z, Lin YC, Li Y. Inoue T and Fivaz M. “Local positive feedback from PI3K to Ras drives cell polarization and migration” Molecular Biology of the Cell (doi:10.1091/mbc.E12-12-0905)PubMed ReferenceLin YC, Su S. and Inoue T. “Visualizing Molecular Diffusion through Passive Permeability Barriers in Cells: Conventional and Novel Approaches“ Current Opinion in Chemical Biology 2013 (doi:10.1016/j.cbpa.2013.04.027)PubMed ReferenceLin YC, Liu TY, Razavi S and Inoue T. “Rapidly Reversible Manipulation of Molecular Activities Using Dual Chemical Dimerizers” Angewandte Chemie 52, 6450 (2013)PubMed ReferenceLin YC, Niewiadomski P, Lin B, Nakamura H, Phua SC, Jiao J, Levchenko A, Inoue T, Rohatgi T, and Inoue T. “Chemically-inducible diffusion trap reveals molecular sieve-like barrier at primary cilia“ Nature Chemical Biology 9, 437 (2013)PubMed Reference
Note: “Research on cilia heats up: Implications for hearing vision loss and kidney disease” Press release, Featured in “ChemBioVault”, “New cilia research could have implications for kidney disease” (American Society of Nephrology, In The Loop), “New clues about molecular composition of cilia” MIGMS Latest News, “Cilia Admit Large Cytosolic Proteins”, Kidney News, “Signaling: Shifting at Ciliary Base” News & Views, Nature Chemical BiologyDeRose R, Miyamoto T and Inoue T. “Manipulating signaling at will: chemically-inducible dimerization (CID) techniques resolve problems in cell biology“ Pfülgers Archiv 465, 409-417 (2013)PubMed ReferenceMiyamoto T, Razavi S, DeRose R, and Inoue T. “Synthesizing Biomolecule-based Boolean Logic Gates” ACS Synthetic Biology 2, (2), 72-82 (2013)Note: “Podcast” (ACS Synthetic Biology)PubMed Reference
Sheikh Zayed TowerBaltimore, MD 21287
707 N. Broadway, Rm 400GBaltimore, MD 21205
Office Phone: 410-502-8279
Lab Phone: 443-923-2754