Roger Y. Tsien

Roger Yonchien Tsien is a co-founder of Aurora Biosciences Corporation, which used GFP for high-throughput drug screening and of Senomyx, a company which licenses GFP for applications in flavorings and fragrances.

Tsien has received numerous awards for his work and is a member of the Institute of Medicine, American Academy of Arts and Sciences, US National Academy of Sciences and Britain’s Royal Society. He was awarded the 2008 Nobel Prize in chemistry for his discovery and development of the green fluorescent protein (GFP) the “glowing proteins” that make some jellyfish and corals luminous, with the help of other chemists: Martin Chalfie and Osamu Shimomura.

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Roger Tsien
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1968 National 1st Prize, Westinghouse Science Talent Search

1969 Detur Prize, Harvard College

1978 Gedge Prize, University of Cambridge

1989 Javits Neuroscience Investigator Award, National Institute of Neurological Disorders and stroke

1991 Young Scientist Award, Passano Foundation

1991 W. Alden Spencer Award in Neurobiology, Columbia University

1995 Artois-Baillet-Latour Health Prize, Belgium

1995 Gairdner Foundation International Award, Canada

1995 Basic Research Prize, American Heart Association

1998 Award for Innovation in High Throughput Screening, Society for Biomolecular Screening

2000 Pearse Prize, Royal microscopical society

2002 ACS Award for Creative Invention, American Chemical society

2002 Christian B. Anfinsen Award, Protein Society

2002 Heineken Prize for Biochemistry and Biophysics, Royal Netherlands Academy of Arts and sciences

2002 Max Delbrück Medal, Max Delbrück Centrum für Molekulare Medizin, Berlin

2004 Wolf prize in medicine, Israel

2004 Keio medical science prize, Japan

2004 UCSD Chancellor’s Associates Award for Excellence in Science & Engineering Research, UC San Diego

2004 Perl Prize in Neuroscience, University of North Carolina

2005 J.Allyn Taylor International Prize in Medicine, Robarts Research Institute, Canada

2006 ABRF Award, Association of Biomolecular Resource Facilities

2006 Lewis S. Rosenstiel Award for Distinguished Work in the Basic Medical Sciences, Brandeis University

2007 BioPharma Leadership Award, the 6th Annual San Diego BioPharma Conference, san Diego, California

Us Department of Defense DoD Breast Cancer Innovator Award

2008 Nobel prize in Chemistry, Sweden

2008 E.B. Wilson medal, American society for Cell Biology

2009 Distinguished Science and Technology Award, The 2009 Asian American Engineers of the Year AAEoY Award

2009 Lifetime Innovation Award, UC San Diego

2009 AHA Distinguished Scientists, American Heart Association

2009 Molecular Imaging Achievement Award, Society of Molecular Imaging

2010 General President Gold Medal, the 97th Indian science Congress, India

2010 Spiers Memorial Award, Royal Society of Chemistry, UK

1.    Roger Y. Tsien 2010. Fluorescence readouts of biochemistry in live cells and organisms. In Molecular Imaging: Principles and Practice, ed. by R. Weissleder, S.S. Gambhir, B.D. Ross, A. Rehemtulla. People’s Medical Publishing House – USA. Chapter 48, pp. 808-828
2.    Roger Y. Tsien 2009. Constructing and exploiting the fluorescent protein paintbox (Autobiography + Nobel Lecture), in Les Prix Nobel 2008, pp. 171-214. Nobel Lecture reprinted (2009) in Angewandte Chemie Intl. Edition 48: 5612-5626.
3.    Roger Y. Tsien 2009 Constructing and Exploiting the Fluorescent Protein Paintbox (Nobel Lecture). Angew. Chem. Int. Ed. 48: 5612 – 5626
4.    Wang, L., and Tsien, R.Y. 2006. Evolving proteins in mammalian cells using somatic hypermutation. Nature Protocols 1: 1346-1350.
5.    Stephen R. Adams & Roger Y. Tsien 2006 Imaging the influx of cell-penetrating peptides into the cytosol of individual cells. Chapter 29 in: Handbook of Cell-Penetrating Peptides, ed by Ulo Langel (2nd edition). CRC 505-512.
6.    Amy E. Palmer and Roger Y. Tsien 2006 Measuring calcium signaling using genetically targetable fluorescent indicators. Nature Protocols, Vol 1: 1057-1065.
7.    Ben N. G. Giepmans, Stephen R. Adams, Mark H. Ellisman & Roger Y. Tsien 2006 The fluorescent toolbox for assessing protein location and function. Science. 312: 217-224.
8.    Zacharias, D.A., and Tsien, R.Y. Molecular biology and mutation of green fluorescent protein. Chapter 5 in: Green Fluorescent Protein: Properties, Applications, and Protocols, ed. by M. Chalfie and S.R. Kain (2nd edition). John Wiley & Sons. This article is listed in Medline as Methods Biochem. Anal. 2006; 47: 83-120
9.    Tsien, R.Y. 2005. Breeding molecules to spy on cells, in The Harvey Lectures: Series 99, 2003-2004. Harvey Society, 2005
10.    Nathan C. Shaner, Paul A. Steinbach, & Roger Y. Tsien. 2005 . A guide to choosing fluorescent proteins, Nature Methods, Vol. 2: 905 – 909
11.    Tsien, R.Y. 2003 Imagining imaging’s future. Nature Reviews Molecular Cell Biology 4: SS16-SS21
12.    Zhang, J., Campbell, R.E., Ting, A. and Tsien, R.Y. 2002. Creating new fluorescent probes for cell biology. Nature Review Molecular Biology 3: 906-918.
13.    Miyawaki, A., and Tsien, R.Y. 2000. Monitoring protein conformations and interactions by fluorescence resonance energy transfer between mutants of green fluorescent protein. Methods in Enzymology 327: 472-500.
14.    Wu, M.M., Llopis, J., Adams, S., McCaffery, J.M., Teter, K., Kulomaa, M.S., Machen, T.E.,Moore,H.-P.H., and Tsien, R.Y. 2000 Studying organelle physiology with fusion protein-targeted avidin and fluorescent biotin conjugates. Methods in Enzymology.327: 546-564.
15.    Griffin, B.A., Adams, S.R., Jones, J., and Tsien, R.Y. 2000. Fluorescent labeling of recombinant proteins in living cells with FlAsH 2001. Methods in Enzymology. 327: 565-578.
16.    Zacharias, D.A., Baird, G.S., and Tsien, R.Y. 2000. Recent advances in technology for measuring and manipulating cell signals. Current Opinion in Neurobiology 10: 416-421.
17.    Tsien, R.Y. 1999. Monitoring Cell Calcium. In Calcium as a Cellular Regulator, ed. by E. Carafoli and C. Klee. New York: Oxford University Press, pp. 28-54.
18.    Tsien, R.Y. 1998. The Green Fluorescent Protein. Annu. Rev. Biochemistry 67: 509-544. Tsien. R.Y. and Pozzan T. 1989. Measurement of Cytosolic Free Ca2+ with Quin2. Method in Enzymology. 172: 230-244.
19.    Xiaokun Shu, Varda Lev-Ram, Thomas J. Deerinck, Yingchuan Qi, Ericka B. Ramko, Michael W. Davidson, Yishi Jin, Mark H. Ellisman, Roger Y. Tsien 2001. A Genetically Encoded Tag for Correlated Light and Electron Microscopy of Intact Cells, Tissues, and Organisms. Plosbiology, 9:1-10
20.    Michael A Whitney, Jessica L Crisp, Linda T Nguyen, Beth Friedman, Larry A Gross, Paul Steinbach, Roger Y Tsien & Quyen T Nguyen 2011. Fluorescent peptides highlight peripheral nerves during surgery in mice. Nature Biotech: Advance Online Publication
21.    Amy P. Wu, Michael A. Whitney, Jessica L. Crisp, Beth Friedman, Roger Y. Tsien, Quyen T. Nguyen 2011. Improved Facial Nerve Identification with Novel Fluorescently Labeled Probe. Laryngoscope 000: 1-6
22.    Richard Ting, Todd A. Aguilera, Jessica L. Crisp, David J. Hall, William C. Eckelman, David R. Vera, and Roger Y. Tsien 2010. Fast 18F Labeling of a Near-Infrared Fluorophore Enables Positron Emission Tomography and Optical Imaging of Sentinel Lymph Nodes. Bioconjugate Chem., 21: 1811-1819
23.    Ouyang, M., Huang, H., Shaner, N.C., Remacle, A.G., Shiryaev, S.A., Strongin, A.Y., Tsien, R.Y., and Wang, Y. 2010. Simultaneous visualization of protumorigenic Src and MT1-MMP activities with fluorescence resonance energy transfer. Cancer Research 70: 2204-221
24.    Whitney, M., Crisp, J.L., Olson, E.S., Aguilera, T.A., Gross, L.A., Ellies, L.G., and Tsien, R.Y. 2010. Parallel in vivo and in vitro selection using phage display identifies protease dependent tumor targeting peptides. J. Biol. Chem. 285: 22532-22541
25.    Emilia S. Olson, Tao Jiang, Todd A. Aguilera, Quyen T. Nguyen, Lesley G. Ellies, Miriam Scadeng, and Roger Y. Tsien 2010 Activatable cell penetrating peptides linked to nanoparticles as dual probes for in vivo fluorescence and MR imaging of proteases. Proc. Natl. Acad. Sci. 107 : 4311–4316
26.    Quyen T. Nguyen, Emilia S. Olson, Todd A. Aguilera, Tao Jiang, Miriam Scadeng, Lesley G. Ellies,and Roger Y. Tsien 2010 Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival. Proc. Natl. Acad. Sci. 107 : 4317–4322
27.    Graham T. Dempsey, Mark Bates, Walter E. Kowtoniuk, David R. Liu, Roger Y. Tsien, and Xiaowei Zhuang 2009 Photoswitching Mechanism of Cyanine Dyes. J Am. Chem. Soc. 131: 18192–18193
28.    Michael Z. Lin, Michael R. McKeown, Ho-Leung Ng, Todd A. Aguilera, Nathan C. Shaner, Robert E. Campbell, Stephen R. Adams, Larry A. Gross, Wendy Ma, Tom Alber, and Roger Y. Tsien 2009 Autofluorescent Proteins with Excitation in the Optical Window for Intravital Imaging in Mammals. Chemistry & Biology 16: 1169–1179
29.    Todd A. Aguilera, Emilia S. Olson, Margaret M. Timmers, Tao Jiang and Roger Y. Tsien 2009 Systemic in vivo distribution of activatable cell penetrating peptides is superior to that of cell penetrating peptides. Integr. Biol. 1: 371–381
30.    Emilia S. Olson, Todd A. Aguilera, Tao Jiang, Lesley G. Ellies, Quyen T. Nguyen, Edmund H. Wong, Larry A. Gross and Roger Y. Tsien 2009 In vivo characterization of activatable cell penetrating peptides for targeting protease activity in cancer. Integr. Biol. 1: 382–393
31.    Fatemeh Madani, Jesper Lind, Peter Damberg, Stephen R. Adams, Roger Y. Tsien, and Astrid O. Graslund 2009 Hairpin Structure of a Biarsenical-Tetracysteine Motif Determined by NMR Spectroscopy. J. AM. CHEM. SOC. 131: 4613–4615
32.    Xiaokun Shu, Antoine Royant, Michael Z. Lin, Todd A. Aguilera, Varda Lev-Ram, Paul A. Steinbach, Roger Y. Tsien 2009 Mammalian Expression of Infrared Fluorescent Proteins Engineered from a Bacterial Phytochrome. Science 324: 804-807
33.    John Y. Lin, Michael Z. Lin, Paul Steinbach, and Roger Y. Tsien 2009 Characterization of Engineered Channelrhodopsin Variants with Improved Properties and Kinetics. Biophysical Journal 96:1803–1814
34.    Stephen R. Adams & Roger Y. Tsien 2008 Preparation of the membrane-permeant biarsenicals FlAsH-EDT2 and ReAsH-EDT2 for fluorescent labeling of tetracysteine-tagged proteins. Nature Protocols 3: 1527-1534
35.    Michael Z. Lin, Jeffrey S. Glenn, and Roger Y. Tsien 2008 A drug-controllable tag for visualizing newly synthesized proteins in cells and whole animals. Proc. Natl. Acad. Sci. 105: 7744–7749
36.    Nathan C Shaner, Michael Z Lin, Michael R McKeown, Paul A Steinbach, Kristin L Hazelwood, Michael W Davidson & Roger Y Tsien 2008 Improving the photostability of bright monomeric orange and red fluorescent proteins. Nature Methods 5, 545-551
37.    Samuel Andrew Hires, Yongling Zhu, and Roger Y. Tsien 2008 Optical measurement of synaptic glutamate spillover and reuptake by linker optimized glutamate-sensitive fluorescent reporters. Proc. Natl. Acad. Sci. 105: 4411–4416
38.    Supplemental 1 Brent R. Martin, Thomas J. Deerinck, Mark H. Ellisman, Susan S.Taylor, and Roger Y.Tsien – Isoform-Specific PKA Dynamics Revealed by Dye-Triggered Aggregation and DAKAP1α-Mediated Localizationin Living Cells. Chemistry & Biology 14, 1031–1042
39.    Oded Tour, Stephen R. Adams, Rex A. Kerr, Rene M. Meijer, Terrence J. Sejnowski, Richard W. Tsien, and Roger Y. Tsien – Calcium Green FlAsH as a genetically targeted small-molecule calcium indicator. Nature Chemical Biology. 3: 423-431
40.    Hui-wang Ai, Nathan C. Shaner, Zihao Cheng, Roger Y. Tsien, and Robert E. Campbell 2007 – Exploration of new chromophore structures leads to the identification of improved blue fluorescent proteins. Biochemistry, 46, 5904-5910
41.    Hauser, C.T., and Tsien, R.Y. 2007 A hexahistidine-Zn2+-dye label reveals STIM1
42.    surface exposure. Proc. Natl. Acad. Sci. 104: 3693–3697
43.    Wang, L., and Tsien, R.Y. 2006. Evolving proteins in mammalian cells using somatic hypermutation. Nature Protocols 1: 1346-1350.
44.    Timothy A. Dunn, Chih-Tien Wang, Michael A. Colicos, Manuela Zaccolo, Lisa M. DiPilato, Jin Zhang, Roger Y. Tsien, and Marla B. Feller 2006 Imaging of cAMP levels and protein kinase A activity reveals that retinal waves drive oscillations in second-messenger cascades. J Neuroscience 26(49): 12807–12815
45.    Guido M. Gaietta, Ben N. G. Giepmans, Thomas J. Deerinck, W. Bryan Smith, Lucy Ngan, Juan Llopis, Stephen R. Adams, Roger Y. Tsien, and Mark H. Ellisman 2006 Golgi twins in late mitosis revealed by genetically encoded tags for live cell imaging and correlated electron microscopy. Proc. Natl. Acad. Sci. 103: 17777–17782
46.    Jeffrey J. Saucerman, JinZhang, Jody C. Martin, Lili X. Peng, Antine E. Stenbit, Roger Y. Tsien, and Andrew D. McCulloch 2006 Systems analysis of PKA-mediated phosphorylation gradients in live cardiac myocytes. Proc. Natl. Acad. Sci. 103: 12923–12928
47.    Xiaokun Shu, Nathan C. Shaner, Corinne A.Yarbrough, Roger Y. Tsien, and S. James Remington 2006 Novel chromophores and buried charges control color in mFruits. Biochemistry 45: 9639-9647
48.    Amy E. Palmer, Marta Giacomello, Tanja Kortemme, Andrew Hires, Varda Lev-Ram, David Baker, and Roger Y. Tsien. 2006 Ca2+ Indicators based on computationally redesigned calmodulin-peptide pairs. Chemistry & Biology 13: 521–530
49.    Jeremy R. Babendure, Jennie L. Babendure, Jian-Hua Ding and Roger Y. Tsien. 2006 Control of mammalian translation by mRNA structure near caps. RNA,12: 851–861.
50.    Brent R. Martin, Ben N.G. Giepmans, Stephen R. Adams & Roger Y. Tsien. 2005 Mammalian cell-based optimization of the biarsenical-binding tetracysteine motif for improved fluorescence and affinity. Nature Biotechnol. 10:1308-1314.
51.    Jin Zhang, Christopher J. Hupfeld, Susan S. Taylor, Jerrold M. Olefsky & Roger Y. Tsien. 2005 Insulin disrupts Beta-adrenergic signaling to protein kinase A adipocytes. Nature, 437: 569-573.
52.    Hoffmann, C., Gaietta, G., Bünemann, M., Adams, S.R., Oberdorff-Maass, S., Behr, B., Vilardaga, J., Tsien, R.Y., Ellisman, M.H., and Lohse, M.J. 2005 A FlAsH-based FRET approach to determine G protein-coupled receptor activation in living cells, Nature Methods 2: 171-176
53.    Yingxiao Wang1, Elliot L. Botvinick, Yihua Zhao, Michael W. Berns, Shunichi Usami, Roger Y. Tsien & Shu Chien 2005 Visualizing the mechanical activation of Src, Nature 434: 1040-1045
54.    JC Goldstein, C Munoz-Pinedo, J-E Ricci, SR Adams, A Kelekar, M Schuler, RY Tsien and DR Green 2005 Cytochrome c is released in a single step during apoptosis, Cell Death and Differentiation 12: 453–462
55.    Tao Jiang, Emilia S. Olson, Quyen T. Nguyen, Melinda Roy, Patricia A. Jennings, and Roger Y. Tsien 2004 Tumor imaging by means of proteolytic activation of cell-penetrating peptides. Proc. Natl. Acad. Sci. 101: 17867-17872.
56.    Nathan C. Shaner, Robert E. Campbell, Paul Steinbach, Ben N. G. Giepmans, Amy E. Palmer and Roger Y. Tsien. 2004 Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma fluorescent protein. Nature Biotech. 22: 1567-1572
57.    Amy E. Palmer, Can Jin, John C. Reed and Roger Y. Tsien 2004 Bcl-2-mediated alterations in endoplasmic reticulum Ca2+ analyzed with an improved genetically encoded fluorescent sensor Proc. Natl. Acad. Sci.101: 17404-17409.
58.    Lei Wang, W. Coyt Jackson, Paul A. Steinbach, and Roger Y. Tsien 2004 Evolution of new nonantibody proteins via iterative somatic hypermutation Proc. Natl. Acad. Sci.101: 16745-16749.
59.    Toshiaki Furuta, Hiroko Takeuchi, Masahiro Isozaki, Yasuhiro Takahashi, Makoto Kanehara, Masazumi Sugimoto, Takayoshi Watanabe, Kousei Noguchi, Timothy M. Dore, Takashi Kurahashi, Michiko Iwamura, and Roger Tsien. 2004 Bhc-cNMPs as either Water -Soluble or Membrane-Permeant Photoreleasable Cyclic Nucleotides for both One- and Two-Photon Excitation. Chem. Biochem. 5: 1119-1128.
60.    Colette T. Dooley, Timothy M. Dore, George T. Hanson, W. Coyt Jackson, S. James Remington, and Roger Y. Tsien 2004 Imaging Dynamic Redox Changes in Mammalian Cells with Green Fluorescent Protein Indicators J. Biol. Chem., May 2004; 279: 22284 – 22293
61.    George T. Hanson, Robert Aggeler, Devin Oglesbee, Mark Cannon, Roderick A. Capaldi, Roger Y. Tsien, and S. James Remington 2004 Investigating Mitochondrial Redox Potential with Redox-sensitive Green Fluorescent Protein Indicators J. Biol. Chem., Mar 2004; 279: 13044 -13053.
62.    Ju, W., Morishita, W., Tsui, J., Gaietta, G., Deerink, T.J., Adams, S.R., Garner, C.G., Tsien, R.Y., Ellisman, M.H., and Malenka, R.C. 2004 Activity-dependent regulation of dendritic sysnthesis and trafficking of AMPA receptors. Nat. Neurosci. 7: 244-253
63.    Ray, P., De, A., Min, J-J., Tsien, R.Y. and Gambhir, S.S. 2004 Imaging tri-fusion multimodality reporter gene expression in living subjects. Cancer Res. 64: 1323-1330.
64.    Lev-Ram, V., Mehta, S.B., Kleinfeld, D., and Tsien, R.Y. 2003 Reversing cerebellar long-term depression. Proc. Natl. Acad. Sci. 100: 15989-15993
65.    Hasegawa,S., Jackson, W.C., Tsien, R.Y., and Rao, J-H. 2003 Imaging tetrahymena ribozyme splicing activity in single live mammalian cells Proc. Natl. Acad. Sci. 100: 14892–14896.
66.    Tour,O., Meijer,R.M., Zacharias,D.A., Adams.S.R. and Tsien, R.Y. 2003 Genetically targeted chromophore-assisted light inactivation Nat.Biotech 21: 1505-1508.
67.    Babendure, J.R., Adams,S.R.and Tsien, R.Y. 2003 Aptamers Switch on Fluorescence of Triphenylmethane Dyes. J. Am. Chem. Soc. 125: 14716-14717.
68.    Gao, W., Xing, B., Tsien, R.Y., and Rao, J-H. 2003. Novel fluorogenic substrates for imaging B-Lactamase Gene Expression. J.Am.Chem.Soc. 125: 11146-11147.
69.    Violin, J.D., Zhang, J., Tsien, R.Y., and Newton, A.C. 2003. A genetically encoded fluorescent reporter reveals oscillatory phosphorylation by protein kinase C. J. Cell Biol. 161: 899-909.
70.    Tsai, P.S., Friedman, B., Ifarraguerri, A.I., Thompson, B.D., Lev-Ram, V., Schaffer, C.B., Xiong, Q., Tsien, R.Y., Squier, J.A., and Kleinfeld, D. 2003. All-optical histology using ultrashort laser pulses. Neuron 39: 27-41
71.    Yu D, Baird GS, Tsien RY, Davis RL. 2003 Detection of calcium transients in Drosophila mushroom body neurons with camgaroo reporters. J Neuroscience 23: 64-72.
72.    Lev-Ram, V., Wong, S.T., Storm, D.R., and Tsien, R.Y. 2002 A new form of cerebellar long-term potentiation is postsynaptic and depends on nitric oxide but not cAMP. Proc. Natl. Acad. Sci. 99: 8389-8393.
73.    Campbell, R.E., Tour, O., Palmer, A.E., Steinbach, P., Baird, G.S., Zacharias, D.A., and Tsien, R.Y. 2002. A monomeric red fluorescent protein. Proc. Natl. Acad. Sci. 99: 7877-7882.
74.    Adams, S.R., Campbell, R.E., Gross, L.A., Martin, B.R., Walkup, G.K., Yao, Y., Llopis, J., and Tsien, R.Y. 2002. New biarsenical ligands and tetracysteine motifs for protein labeling in vitro and in vivo: synthesis and biological applications. J. Am. Chem. Soc., 124: 6063-6076.
75.    Zacharias,D.A., Violin,J.D., Newton,A.C., Tsien R.Y. 2002 Partitioning of Lipid-Modified Monomeric GFPs into Membrane Microdomains of Live Cells Science 296: 913-916.
76.    Gaietta, G., Deerinck, T.J., Adams, S.R., Bouwer, J., Tour,O., Laird, D.W., Sosinsky, G.E., Tsien, R.Y. and Ellisman, M.H. 2002 Multicolor and Electron Microscopic Imaging of Connexin Trafficking. Science 296: 503-507.
77.    Zhang, J., Ma, Y., Taylor, S.S., and Tsien, R.Y. 2001 Genetically encoded reporters of protein kinase A activity reveal impact of substrate tethering Proc. Natl. Acad. Sci. 98: 14997-15002.
78.    Ting, A.Y., Kain, K.H., Klemke, R.L. and Tsien, R.Y. 2001 Genetically encoded fluorescent reporters of protein tyrosine kinase activities in living cells Proc.Natl. Acad. Sci 98: 15003-15008.
79.    Wu, M.M., Grabe, M., Adams, S., Tsien, R. Y., Moore, H-P. H., and Machen, T. E. 2001. Mechanisms of pH regulation in the regulated secretory pathway. J. Biol. Chem. 276: 33027-33035.
80.    Burdette, S.C., Walkup, G.K., Spingler, B., Tsien, R.Y. and Lippard, S.J. 2001. Fluorescent sensors for Zn2+ based on a fluorescein platform: Synthesis, properties and intracellular distribution. J. Am. Chem. Soc. 123: 7831-7841.
81.    Ando, H., Furuta, T., Tsien, R.Y., and Okamoto, H. 2001. Photo-mediated gene activation using caged RNA/DNA in zebrafish embryos. Nature Genetics 28: 317-325.
82.    Chan, F, Siegel, R.M., Zacharias, D., Swofford, R., Holmes, K.L., Tsien, R.Y., Lenardo, M.J. (2001) Fluorescence Resonance Energy Transfer Analysis of Cell Surface Receptor Interactions and Signaling Using Spectral Variants of the Green Fluorescent Protein Cytometry. 44: 361-368
83.    Griesbeck,O.; Baird,G.S.; Campbell,R.E.; Zacharias,D.A.; Tsien,R.Y. 2001 Reducing the environmental sensitivity of yellow fluorescent protein. mechanism and applications. J.Biol.Chem. 276: 29188-29194.
84.    Honda, A., Adams, S.R., Sawyer, C.L., Lev-Ram, V., Tsien, R.Y., and Dostmann, W.R.G. 2001. Spatiotemporal dynamics of guanosine 3’,5’-cyclic monophosphate revealed by a genetically encoded, fluorescent indicator. Proc. Natl. Acad. Sci., 98: 2437-2442..
85.    Kapahi, P., Takahashi, T., Natoli, G., Adams, S.R., Chen, Y., Tsien, R.Y. and Karin, M. 2000. Inhibition of NF-κB activation by arsenite through reaction with a critical cysteine in the activation loop of IκB kinase. J. Biol. Chem. 275: 36062-36066.
86.    Heikal, A.A., Hess, S.T., Baird, G.S., Tsien, R.Y., and Webb, W.W. 2000. Molecular Spectroscopy and Dynamics of Intrinsically Fluorescent Proteins: Coral Red (DsRed) and Yellow (Citrine). Proc. Natl. Acad. Sci., 97: 11996-12001
87.    Gross, L.A., Baird, G.S., Hoffman, R.C., Baldridge, K.K., and Tsien, R.Y. 2000. The structure of the chromophore within DsRed, a red fluorescent protein from coral. Proc. Natl. Acad. Sci., 97: 11990-11995. Supplement
88.    Baird, G.S., Zacharias, D.A., and Tsien, R.Y. 2000. Biochemistry, mutagenesis, and oligomerization of dsRed, a red fluorescent protein from coral. Proc. Natl. Acad. Sci., 97: 11984-11989.
89.    Allen, G.J., Chu, S.P., Schumacher, K., Shimazaki, C.T., Vafeados, D., Kemper, A., Hawke, S.D., Tallman, G., Tsien, R.Y., Harper, J.F., Chory, J., and Schroeder, J.I. 2000. Alteration of stimulus-specific guard cell calcium oscillations and stomatal closing in Arabidopsis det3 mutant. Science 289: 2338-2342.
90.    Siegel, R.M., Frederiksen, J.K., Zacharias,D.A., Chan, F.K.-M., Johnson, M., Lynch, D., Tsien, R.Y., and Lenardo, M.J. 2000. Fas preassociation required for apoptosis signaling and dominant inhibition by pathogenic mutations. Science 288: 2354-2357.
91.    Kerr, R., Lev-Ram, V., Baird, G., Vincent, P., Tsien, R.Y., Schafer, W.R. 2000. Optical imaging of calcium transients in neurons and pharyngeal muscle of C. elegans. Neuron 26: 583-594. Walkup, G.K., Burdette, S.C., Lippard, S.J., and Tsien, R.Y. 2000. A new cell-permeable fluorescent probe for Zn2+. J. Amer. Chem. Soc. 122: 5644-5645.
92.    Matsuyama, S., Llopis, J., Deveraux, Q.L., Tsien, R.Y., and Reed, J.C. 2000. Changes in intramitochondrial and cytosolic pH: early events that modulate caspase activation during apoptosis. Nature Cell Biology 2: 318-325.
93.    Llopis, J., Westin, S., Ricote, M., Wang, J., Cho, C.Y., Kurokawa, R., Rose, D.W., Rosenfeld, M.G., Tsien, R.Y., and Glass, C.K. 2000. Ligand-dependent interactions of coactivators SRC-1 and PBP with nuclear hormone receptors can be imaged in live cells and are required for transcription. Proc. Natl. Acad. Sci. USA 97: 4363-4368.
94.    Wu, M.M., Llopis, J., Adams, S., McCaffery, J.M., Kulomaa, M.S., Machen, T.E., Moore, H.-P.H., and Tsien, R.Y. 2000. Organelle pH studies using targeted avidin and fluorescein-biotin. Chemistry & Biology 7: 197-209.
95.    Zaccolo, M., De Giorgi, F., Cho, C.Y., Feng, L., Knapp, T., Negulescu, P.A., Taylor, S.S., Tsien, R.Y., and Pozzan, T. 2000. A genetically encoded, fluorescent indicator for cAMP in living cells. Nature Cell Biology 2: 25-29.
96.    Thomas, D., Lipp, P., Tovey, S.C., Berridge, M.J., Li, W., Tsien, R.Y., and Bootman, M.D. 2000. Microscopic properties of elementary Ca2+ release sites in non excitable cells. Current Biology 10: 8-15.
97.    Baird, G.S., Zacharias, D.A., and Tsien, R.Y. 1999. Circular permutation and receptor insertion into green fluorescent proteins. Proc. Natl. Acad. Sci. USA 96: 11241-11246.
98.    Yao, Y., Ferrer-Montiel, A.V., Montal, M., and Tsien, R.Y. 1999. Activation of store-operated Ca2+ current in Xenopus oocytes requires SNAP-25 but not a diffusible messenger. Cell 98: 475-485.
99.    Cacciatore, T.W., Brodfuehrer, P.D., Gonzalez, J.E., Jiang, T., Adams, S.R., Tsien, R.Y., Kristan, W.B., and Kleinfeld, D. 1999. Identification of neural circuits by imaging coherent electrical activity with FRET-based dyes. Neuron 23: 449-459.
100.    Li, C.-J., Heim, R., Lu, P., Pu, Y., Tsien, R.Y., and Chang, D.C. 1999. Dynamic redistribution of calmodulin in HeLa cells during cell division as revealed by a GFP calmodulin fusion protein technique. J. Cell Sci. 112: 1567 1577.
101.    Lin, P., Yao, Y., Hofmeister, R., Tsien, R.Y., and Farquhar, M.G. 1999. Overexpression of CALNUC (Nucleobindin) increases agonist and thapsigargin releasable Ca2+ storage in the Golgi. J. Cell Biol. 145: 279-289.
102.    Fan, G.Y., Fujisaki, H., Miyawaki, A., Tsay, R.-K., Tsien, R.Y., and Ellisman, M.H. 1999. Video-rate scanning two-photon excitation fluorescence microscopy and ratio imaging with yellow cameleons. Biophys. J. 76: 2412-2420.
103.    Miyawaki, A., Griesbeck, O., Heim, R., and Tsien, R.Y. 1999. Dynamic and quantitative Ca2+ measurements using improved cameleons. Proc. Natl. Acad. Sci. USA 96: 2135-2140.
104.    Furuta, T., Wang, S. S.-H., Dantzker, J.L., Dore, T.M., Bybee, W.J., Callaway, E.M., Denk, W., and Tsien, R.Y. 1999. Brominated 7-hydroxycoumarin-4-ylmethyls: Novel photolabile protecting groups with biologically useful cross-sections for two photon photolysis. Proc. Natl. Acad. Sci. USA 96: 1193-1200.
105.    Brown, E.B., Shear, J.B., Adams, S.R., Tsien, R.Y., Webb, W.W. 1999. Photolysis of caged calcium in femtoliter volumes using two-photon excitation. Biophys. J. 76: 489-499.
106.    Raz, E., Zlokarnik, G., Tsien, R.Y., and Driever, W. 1998. b-Lactamase as a marker for gene expression in live zebrafish embryos. Developmental Biol. 203: 290-294.
107.    Griffin, B.A., Adams, S.R., and Tsien, R.Y. 1998. Specific covalent labeling of recombinant protein molecules inside live cells. Science 281: 269-272.
108.    Llopis, J., McCaffery, J.M., Miyawaki, A., Farquhar, M.G., and Tsien, R.Y. 1998. Measurement of cytosolic, mitochondrial, and Golgi pH in single living cells with green fluorescent proteins. Proc. Natl. Acad. Sci. USA 95: 6803-6808.
109.    Li, W., Llopis, J., Whitney, M., Zlokarnik, G., and Tsien, R.Y. 1998. Cell-permeant caged InsP3 ester shows that Ca2+ spike frequency can optimize gene expression. Nature 392: 936-941.
110.    Jiang, T., Sweeney, G., Rudolf, M., Klip, A., Traynor-Kaplan, A., Tsien, R.Y. 1998. Membrane-permeant esters of phosphatidylinositol-3,4,5-trisphosphate. J. Biol. Chem. 273: 11017-11024.
111.    Zlokarnik, G., Negulescu, P.A., Knapp, T.E., Mere, L., Burres, N., Feng, L., Whitney, M., Roemer, K., and Tsien, R.Y. 1998. Quantitation of transcription and clonal selection of single living cells using beta-lactamase as reporter. Science 279: 84-88.
112.    Eckmann, L., Rudolf, M.T., Ptasznik, A., Schultz, C., Jiang, T., Wolfson, N., Tsien, R., Fierer, J., Shears, S.B., Kagnoff, M.F., Traynor-Kaplan, A.E. 1997. D-myo-inositol 1,4,5,6-tetrakisphosphate produced in human intestinal epithelial cells in response to Salmonella invasion inhibits phosphoinositide 3-kinase signaling pathways. Proc. Natl. Acad. Sci. 94: 14456-14460.
113.    Adams, S.R., Lev-Ram, V., and Tsien, R.Y. 1997. A new caged Ca2+, azid-1, is far more photosensitive than nitrobenzyl-based chelators. Chemistry & Biology 4: 867-878.
114.    Miyawaki, A., Llopis, J., Heim, R., McCaffery, J.M., Adams, J.A., Ikura, M., and Tsien, R.Y. 1997. Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin. Nature 388: 882-887.
115.    Wachter, R.M., King, B.A., Heim, R., Kallio, K., Tsien, R.Y., Boxer, S., and Remington, S.J. 1997. Crystal structure and photodynamic behavior of the blue-emission variant Y66H/Y145F of green fluorescent protein. Biochemistry 36: 9759-9765.
116.    Li, W., Schultz, C., Llopis, J., and Tsien, R.Y. 1997. Membrane-permeant esters of inositol polyphosphates: chemical syntheses and biological applications. Tetrahedron 53: 12017-12040.
117.    Dickson, R.M., Cubitt, A.B., Tsien, R.Y., and Moerner, W.E. 1997. On/off blinking and switching behaviour of single green fluorescent protein molecules. Nature 388: 355
118.    Lev-Ram, V., Jiang, T., Wood, J., Lawrence, D.S., and Tsien, R.Y. 1997. Synergies and coincidence requirements between NO, cGMP, and Ca2+ in the induction of cerebellar long-term depression. Neuron 18: 1025-1038.
119.    Yao, Y. and Tsien, R.Y. 1997. Calcium current activated by depletion of calcium stores in Xenopus oocytes. J. Gen. Physiol. 109: 703-715
120.    Lev-Ram, V., Nebyelul, Z., Ellisman, M.H., Huang, P.L., and Tsien, R.Y. 1997. Absence of cerebellar long-term depression in mice lacking neuronal nitric oxide synthase. Learning & Memory 3: 169-177
121.    Gonzalez, J.E. and Tsien, R.Y. 1997. Improved indicators of cell membrane potential that use fluorescence resonance energy transfer. Chemistry & Biology 4: 269-277.
122.    Brejc, K., Sixma, T.K., Kitts, P.A., Kain, S.R., Tsien, R.Y., Ormö, M., and Remington, S.J. 1997. Structural basis for dual excitation and photoisomerization of the Aequorea victoria green fluorescent protein. Proc. Natl. Acad. Sci. 94: 2306-2311.
123.    Arancio, O., Kiebler, M., Lee, C.J., Lev-Ram, V., Tsien, R.Y., Kandel, E.R., and Hawkins, R.D. 1996. Nitric oxide acts directly in the presynaptic neuron to produce long-term potentiation in cultured hippocampal neurons. Cell 87: 1025-1035.
124.    Hempel, C., Vincent, P., Adams, S.R., Tsien, R.Y., and Selverston, A.I. 1996. Spatio-temporal dynamics of cyclic AMP signals in an intact neural circuit. Nature 384: 166-169.
125.    Scheenen, W.J.J.M., Makings, L.R., Gross, L.R., Pozzan, T., and Tsien, R.Y. 1996. Photodegradation of indo-1 and its effect on apparent Ca2+ concentrations. Chemistry & Biology 3: 765-774.
126.    Ormö, M., Cubitt, A.B., Kallio, K., Gross, L.A., Tsien, R.Y., and Remington, S.J. 1996. Crystal structure of Aequorea victoria green fluorescent protein. Science 273: 1392-1395.
127.    Rizzuto, R., Brini, M., De Georgi, F., Rossi, R., Heim, R., Tsien, R.Y., and Pozzan, T. 1996. Double labelling in vivo of subcellular structures with organelle-targeted GFP mutants. Current Biol. 6: 183-188.
128.    Heim, R., and Tsien, R.Y. 1996. Engineering green fluorescent protein for improved brightness, longer wavelengths, and fluorescence resonance energy transfer. Current Biol. 6: 178-182.
129.    Gonzalez, J.E., and Tsien, R.Y. 1995. Voltage sensing by fluorescence resonance energy transfer in single cells. Biophys. J. 69: 1272-1280.
130.    Wen, W., Meinkoth, J.L., Tsien, R.Y., and Taylor, S.S. 1995. Identification of a signal for rapid export of proteins from the nucleus. Cell 82: 463-473.
131.    Lev-Ram, V., Makings, L.R., Keitz, P.F., Kao, J.P.Y., and Tsien, R.Y. 1995. Long-term depression in cerebellar Purkinje neurons results from coincidence of nitric oxide and depolarization-induced Ca2+ transients. Neuron 15: 407-415.
132.    Vajanaphanich, M., Schultz, C., Tsien, R.Y., Traynor-Kaplan, A.E., Pandol, S.J. and Barrett, K.E. 1995. Cross-talk between calcium and cAMP-dependent intracellular signalling pathways: implications for synergistic secretion in T84 colonic epithelial cells and rat pancreatic acinar cells. J. Clin. Invest. 96: 386-393
133.    Heim, R., Cubitt, A.B., and Tsien, R.Y. 1995. Improvement of green fluorescent protein by site-directed mutations. Nature 373: 663-664.
134.    Bacskai, B.J., Wallén, P., Lev-Ram, V., Grillner, S., and Tsien, R.Y. 1995. Activity-related calcium dynamics in lamprey motoneurons as revealed by video-rate confocal microscopy. Neuron 14: 19-28.
135.    Randriamampita, C., and Tsien, R.Y. 1995. Degradation of a calcium influx factor (CIF) can be blocked by phosphatase inhibitors or chelation of Ca2+. J. Biol. Chem. 270: 29-32.
136.    Wen, W., Harootunian, A.T., Adams, S.R., Feramisco, J., Tsien, R.Y., Meinkoth, J.L., and Taylor, S.S. 1994. Heat stable protein kinase inhibitors of cAMP-dependent protein kinase carry a nuclear export signal. J. Biol. Chem. 269: 32214-32220.
137.    Heim, R., Prasher, D.C., and Tsien, R.Y. 1994. Wavelength mutations and post-translational autooxidation of green fluorescent protein. Proc. Natl. Acad. Sci. USA 91: 12501-12504.
138.    Schultz, C., Vajanaphanich, M., Genieser, H.G., Jastorff, B., Barrett, K.E., and Tsien, R.Y. 1994. Membrane-permeant derivatives of cyclic AMP optimized for high potency, prolonged activity, or rapid reversibility. Mol. Pharmacol. 46: 702-708.
139.    Vajanaphanich, M., Schultz, C., Rudolf, M.T., Wasserman, M., Enyedi, P., Craxton, A., Shears, S.B., Tsien, R.Y. Barrett, K.E., and Traynor-Kaplan, A. 1994. Long-term uncoupling of chloride secretion from intracellular calcium levels by Ins(3,4,5,6)P4. Nature 371: 711-714.
140.    Ranganathan, R., Bacskai, B., Tsien, R.Y., and Zuker, C.S. 1994. Cytosolic calcium transients: spatial localization and role in Drosophila photoreceptor cell function. Neuron 13: 837-848.
141.    Deerinck, T.J., Martone, M.E., Lev Ram, V., Green, D.P.L, Tsien, R.Y., Spector, D.L., Huang, S., and Ellisman, M.H. 1994. Fluorescence photooxidation with eosin: A method for high resolution immunolocalization and in situ hybridization detection for light and electron microscopy. J. Cell Biol. 126: 901-910.
142.    Civitelli, R., Bacskai, B.J., Mahaut-Smith, M.P., Adams, S.R., Avioli, L.V., and Tsien, R.Y. 1994. Single-cell analysis of cyclic AMP response to parathyroid hormone in osteoblastic cells. J. Bone Miner. Res. 9: 1407-1417.
143.    Gurantz, D., Harootunian, A.T., Tsien, R.Y., Dionne, V.E., and Margiotta, J.F. 1994. VIP modulates neuronal acetylcholine receptor function by a cyclic AMP-dependent mechanism. J. Neurosci. 14: 3540-3547.
144.    Asmis, R., Randriamampita, C., Tsien, R.Y., and Dennis, E.A. 1994. Intracellular Ca2+, inositol 1,4,5-trisphosphate and additional signalling in the platelet-activating factor of prostaglandin E2 formation in P388D1 macrophage-like cells. Biochem. J. 298: 543-551.
145.    Makings, L.R., and Tsien, R.Y. 1994. Caged nitric oxide: stable, organic molecules from which nitric oxide can be photoreleased. J. Biol. Chem. 269: 6282-6285.
146.    Fantozzi, D.A., Harootunian, A.T., Wen, W., Taylor, S.S., Feramisco, J.R., Tsien, R.Y., and Meinkoth, J.L. 1994. The thermostable inhibitor of cAMP-dependent protein kinase enhances the rate of export of the kinase catalytic subunit from the nucleus. J. Biol. Chem. 269: 2676-2686
147.    Harootunian, A.T., Adams, S.R., Wen, W., Meinkoth, J.L., Taylor, S.S., and Tsien, R.Y. 1993. Movement of the free catalytic subunit of cAMP dependent protein kinase into and out of the nucleus can be explained by diffusion. Mol. Biol. Cell. 4: 993-1002.
148.    Randriamampita, C., and Tsien, R.Y. 1993. Emptying of intracellular Ca2+ stores releases a novel small messenger that stimulates Ca2+ influx. Nature 263: 809-814.
149.    Hagiwara, M., Brindle, P., Harootunian, A.T., Armstrong, R., Rivier, J., Vale, W., Tsien, R.Y., and Montminy, M.R. 1993. Coupling of hormonal stimulation and transcription via the cyclic AMP-responsive factor CREB is rate limited by nuclear entry of protein kinase A. Mol. Cell Biol. 13: 4852-4859.
150.    LaMorte, V.J., Harootunian, A.T., Spiegel, A.M., Tsien, R.Y., and Feramisco, J.R. 1993. Mediation of growth factor induced DNA synthesis and calcium mobilization by Gq and Gi2. J. Cell Biol. 121: 91-99.
151.    Bacskai, B.J., Hochner, B., Mahaut-Smith, M., Adams, S.R., Kaang, B.-K., Kandel, E.R., and Tsien, R.Y. 1993. Spatially resolved dynamics of cAMP and protein kinase A subunits in Aplysia sensory neurons. Science 260: 222-226.
152.    Schultz, C., Vajanaphanich, M., Harootunian, A.T., Sammak, P.J., Barrett, K.E., and Tsien, R.Y. 1993. Acetoxymethyl esters of phosphates: enhancement of the permeability and potency of cAMP. J. Biol. Chem. 268: 6316-6322.
153.    Sammak, P.J., Adams, S.R., Harootunian, A.T., Schliwa, M., and Tsien, R.Y. 1992. Intracellular cyclic AMP not Ca2+ determines the direction of vesicle movement in melanophores: direct measurements by fluorescence ratio imaging. J. Cell Biol. 117: 57-72.
154.    Harootunian, A.T., Kao, J.P.Y., Paranjape, S., Adams, S.R., Potter, B.V.L., and Tsien, R.Y. 1991. Cytosolic Ca2+ oscillations in REF52 fibroblasts: Ca2+-stimulated IP3 production or voltage-dependent Ca2+ channels as key positive feedback elements. Cell Calcium 12: 153-164.
155.    Adams, S.R., Harootunian, A.T., Buechler, Y.J., Taylor, S.S., and Tsien, R.Y. 1991. Fluorescence ratio imaging of cyclic AMP in single cells. Nature 349: 694-697.
156.    Harootunian, A.T., Kao, J.P.Y., Paranjape, S., and Tsien, R.Y. 1991. Generation of calcium oscillations in fibroblasts by positive feedback between calcium and IP3. Science 251: 75-78.
157.    Kao, J.P.Y., Alderton, J.M., Tsien, R.Y., and Steinhardt, R.A. 1990. Active involvement of Ca2+ in mitotic progression of Swiss 3T3 fibroblasts. J. Cell Biol. 111: 183-196.
158.    Negulescu, P.A., Harootunian, A., Tsien, R.Y., and Machen, T.E. 1990. Fluorescence measurements of cytosolic free Na concentration, influx and efflux in gastric cells. Cell Regulation 1: 259-268.
159.    Tsien, R.Y., and Harootunian, A.T. 1990. Practical design criteria for a dynamic ratio imaging system. Cell Calcium 11: 93-109.
160.    Harootunian, A.T., Kao, J.P.Y., Eckert, B.K., and Tsien, R.Y. 1989. Fluorescence ratio imaging of cytosolic free Na+ in individual fibroblasts and lymphocytes. J. Biol. Chem. 264: 19458-19467.
161.    Minta, A., and Tsien, R.Y. 1989. Fluorescent indicators for cytosolic sodium. J. Biol. Chem. 264: 19449-19457.
162.    Adams, S.R., Kao, J.P.Y., and Tsien, R.Y. 1989. Biologically useful chelators that take up Ca2+ upon illumination. J. Amer. Chem. Soc. 111: 7957-7968.
163.    Kawanishi, T., Blank, L.M., Harootunian, A.T., Smith, M.T., and Tsien, R.Y. 1989. Ca2+ oscillations induced by hormonal stimulation of individual fura-2-loaded hepatocytes. J. Biol. Chem. 264: 12859-12866.
164.    Kao, J.P.Y., Harootunian, A.T., and Tsien, R.Y. 1989. Photochemically generated cytosolic calcium pulses and their detection by fluo-3. J. Biol. Chem. 264: 8179-8184.
165.    Minta, A., Kao, J.P.Y., and Tsien, R.Y. 1989. Fluorescent indicators for cytosolic calcium based on rhodamine and fluorescein chromophores. J. Biol. Chem. 264: 8171-8178.
166.    Havran, W.L., Poenie, M., Tigelaar, R.E., Tsien, R.Y., and Allison, J.P. 1989. Phenotypic and functional analysis of gd T cell receptor-positive murine dendritic epidermal clones. J. Immunology 142: 1422-1428.
167.    Langlet, C., Guimezanes, A., Kaldy, P., Boyer, C., Buferne, M., Poenie, M., Tsien, R., Leo, O., Bluestone, J., Leserman, L., and Schmitt-Verhulst, A.-M. 1988. Role of Ti/CD3, Thy-1, and Ly-6 in cytolytic T-cell activation analyzed with Ti loss variants. Ann. N.Y. Acad. Sci. 532: 33-43.
168.    Grynkiewicz, G.; Poenie, M.; and Tsien, R.Y. (1985) A new generation of CA2+ indicators with greatly improved fluorescence properties* J.Biol.Chem. 260: 3440-3450
169.    Tsien, R.Y. (1980) New calcium indicators and buffers with high selectivity against magnesium and protons. Biochemisty 19: 2396-2404

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    Professor of Pharmacology and Professor of Chemistry and Biochemistry, University of California, San Diego (UCSD)