个人简介

2003 Todd Visiting Professor of Chemistry, University of Cambridge, England 2003 Konrad Bloch Lectureship, Harvard University 2003 Keith Porter Lectureship, American Society for Cell Biology 2003 Hugh Davson Distinguished Lecturer, American Physiological Society 2002 Max Delbrück Medal, Max Delbrück Centrum für Molekulare Medizin, Berlin 2002 Heineken Prize for Biochemistry and Biophysics, Royal Netherlands Academy of Sciences 2002 Christian B. Anfinsen Award, Protein Society 2002 ACS Award for Creative Invention, American Chemical Society 2000 Pearse Prize, Royal Microscopical Society 2000 Herbert Sober Lectureship, American Society for Biochemistry and Molecular Biology 1998 Elected to the National Academy of Sciences 1998 Elected to American Academy of Arts and Sciences 1998 Award for Innovation in High Throughput Screening, Society for Biomolecular Screening 1995 Gairdner Foundation International Award, Canada 1995 Elected to Institute of Medicine 1995 Basic Research Prize, American Heart Association 1995 Artois-Baillet-Latour Health Prize, Belgium 1991 Young Scientist Award, Passano Foundation 1991 W. Alden Spencer Award in Neurobiology, Columbia University 1989 - Investigator, Howard Hughes Medical Institute 1983-1986 Searle Scholar 1982-1989 Appointed to faculty, University of California, Berkeley 1977-1981 Research Fellow, Gonville and Caius College, Cambridge 1972-1975 Marshall Scholar

研究领域

Biochemistry

We build both small synthetic molecules and genetically encoded macromolecules, preferably working in synergy, to detect and manipulate biochemical signals. Current projects include: 1) Genetically encoded chemosensors: We have created fluorescent sensors of intracellular Ca2+ and of many serine/threonine or tyrosine protein kinase activities by fusing fluorescent proteins with modules that change conformation upon binding Ca2+ or becoming phosphorylated. These sensors open tremendous possibilities for imaging dynamic signal transduction at spatial dimensions ranging from the submicroscopic to entire transgenic organisms. Analogous indicators for redox potential, membrane potential, and synaptic transmitters are under development. 2) Organic synthetic tags targeted by molecular biology: Natural fluorescent proteins are somewhat large and limited in spectroscopic properties. We have shown that a much smaller protein motif containing four cysteines can be specifically labeled in living cells with membrane-permeant small molecules carrying two appropriately spaced arsenic substituents. Such dyes allow pulse-chase determination of the age of individual protein molecules, localization by electron microscopy, and rapid photochemically-induced inactivation. We are pursuing many biological applications as well as developing an independent system involving histidine and Zn2+ rather than cysteines and As(III). 3) Imaging specific mRNAs in intact animals and patients: We are working towards catalytic RNAs that would detect specific mRNAs via highly amplifying, noninvasive nonoptical readouts, eventually to help image and treat tumors that express key cancer-specific mRNAs.

近期论文

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A genetically encoded fluorescent reporter reveals oscillatory phosphorylation by protein kinase C. With J.D. Violin, J. Zhang, and A.C. Newton. J. Cell Biology 161, 899 (2003). A Monomeric Red Fluorescent Protein. With R.E. Campbell, O. Tour, A.E. Palmer, P. Steinbach, G.S. Baird, and D.A. Zacharias. Proc. Natl. Acad. Sci. USA 99, 7877 (2002). A New Form of Cerebellar Long-term Potentiation is Postsynaptic and Depends on Nitric Oxide But Not cAMP. With V. Lev-Ram, S.T. Wong, and D.R. Storm. Proc. Natl. Acad. Sci. USA 99, 8389 (2002). Multicolor and Electron Microscopic Imaging of Connexin Trafficking. With G. Gaietta, T.J. Deerinck, S.R. Adams, J. Bouwer, O. Tour, D.W. Laird, G. Sosinsky, and M.H. Ellisman. Science 296, 503 (2002). New Biarsenical Ligands and Tetracysteine Motifs for Protein Labeling In Vitro and In Vivo: Synthesis and Biological Applications. With S.R. Adams, R.E. Campbell, L.A. Gross, B.R. Martin, G.K. Walkup, Y. Yao, and J. Llopis, J. Am. Chem. Soc. 124, 6063 (2002). Partitioning of Lipid-modified Monomeric GFPs Into Membrane Microdomains of Live Cells. With D.A. Zacharias, J.D.Violin, and A.C. Newton. Science 296, 913 (2002). Genetically Encoded Fluorescent Reporters of Protein Tyrosine Kinase Activities in Living Cells. With A.Y. Ting, K.H. Kain, and R.H. Klemke. Proc. Natl. Acad. Sci. USA 98, 15003 (2001).