个人简介

2007–present Professor, Carnegie Mellon University 2002–2007 Associate Professor, Carnegie Mellon University 1997–2002 Assistant Professor, Carnegie Mellon University 1997 NSF International Research Fellow, University of Copenhagen 1995–1996 NIH Postdoctoral Fellow, Georgia Tech 1993–1994 NIH Postdoctoral Fellow, University of Illinois 1993 Ph.D., University of Arizona

研究领域

Bioorganic & Chemical Biology/Materials & Nanoscience/Sensors/Probes & Imaging

The Armitage group works on projects at the interface of organic chemistry with biological and materials sciences. Our research benefits from collaborative interactions with scientists in two large centers at CMU, the Molecular Biosensor and Imaging Center (MBIC, www.mbic.cmu.edu) and the Center for Nucleic Acids Science and Technology (CNAST, www.cmu.edu/cnast). Both of these interdisciplinary research centers integrate chemistry with molecular and cell biology, providing students with the opportunity to learn a broad portfolio of techniques. Specific projects and collaborations are described below. 1. Bright Fluorescent Labels Based on DNA Nanostructures In this project, we use 1D, 2D and 3D DNA nanostructures as scaffolds for the assembly of fluorescent dye arrays. The DNA allows us to concentrate large numbers of dyes within small volumes of space without allowing self-quenching of the dyes. We rely on synthetic organic chemistry to prepare these “DNA nanotags” and then characterize their fluorescence properties by spectroscopy, time-resolved lifetime measurements, single molecule analysis, flow cytometry and microscopy. We collaborate with the Peteanu group on the characterization experiments and with two groups from the Department of Biological Sciences led by Brooke McCartney and Javier Lopez to apply nanotag labels for intracellular protein and RNA detection. 2. Fluoromodules: A New Class of Fluorescence Imaging Agents Based on Dye-Protein Complexes The goal of this project is to create a catalogue of fluorescent dye-protein complexes that can be used as genetically encodable labels and biosensors for imaging and detection assays. These “fluoromodules” consist of fluorogenic dyes, i.e. dyes that are nonfluorescent in solution, but become fluorescent when conformationally constrained in some way, and specific protein partners that bind to the dye noncovalently, but with high affinity, leading to strong fluorescence from the dye. Synthetic organic chemistry is used to prepare the fluorogenic dyes, while the protein partners are selected from a library consisting of one billion distinct protein molecules. Once an appropriate protein has been isolated from the library for both strong binding and bright fluorescence activation, the “fluorogen-activation protein”, or FAP, can be genetically fused to a protein of interest. When the protein is expressed inside of a cell or at the cell surface, addition of the fluorgenic dye gives a fluorescent signal to the protein, which can then be imaged and tracked using fluorescence microscopy. This project is part of a larger effort in MBIC that includes significant support from the NIH’s National Technology Centers for Networks and Pathways program. We collaborate closely with Alan Waggoner and Peter Berget of the Department of Biological Sciences and MBIC. 3. DNA and RNA Recognition by G Quadruplex-Forming Peptide Nucleic Acids Peptide nucleic acids (PNAs) are synthetic mimics of DNA/RNA in which the hydrogen bonding bases (G,A,C and T) are attached to a peptide-like backbone. Thus, PNA is a chimeric molecule with properties that are reminiscent of both natural proteins and nucleic acids. One of the unique strengths of our department is its development of peptide nucleic acids (PNAs) for applications ranging from chemical biology and biotechnology to nanotechnology and molecular electronics. In most cases, PNAs are designed to have sequences that are complementary to a given DNA or RNA target, allowing the PNA to form a double-helical complex with the target via Watson-Crick base pairing. In collaboration with Danith Ly’s group, we have been designing a special class of PNAs that form “guanine quadruplexes” with specific DNA and RNA targets. This binding mode relies on the PNA and the target nucleic acid to have similar, guanine-rich sequences. Recognition still relies on hydrogen-bond formation, but instead of a G-C pair, the basic unit is a G tetrad, in which the PNA and the DNA/RNA each provide two guanines to a given tetrad. The G-rich target sequences in DNA and RNA have profound biological importance, having been implicated in the regulation of gene expression in diseases ranging from cancer to malaria. Thus, targeting PNAs to these regions should interfere with gene expression, providing important chemical tools for understanding the molecular basis for these diseases and potential therapeutics. We collaborate with Danith Ly on this project.

近期论文

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Strand Invasion of DNA Quadruplexes by PNA: Comparison of Homologous and Complementary Hybridization. Gupta Anisha; Lee Ling-Ling; Roy Subhadeep; Tanious Farial A; Wilson W David; Ly Danith H; Armitage Bruce A. Chembiochem : a European journal of chemical biology (2013). DOI: 10.1002/cbic.201300263 Antitumor Effects of EGFR Antisense Guanidine-Based Peptide Nucleic Acids in Cancer Models. Sufi M. Thomas, Bichismita Sahu, Srinivas Rapireddy, Raman Bahal, Sarah E. Wheeler, Eva M. Procopio, Joseph Kim, Sonali C. Joyce, Sarah Contrucci, Yun Wang, Simion I. Chiosea, Kira L. Lathrop, Simon Watkins, Jennifer R. Grandis, Bruce A. Armitage, and Danith H. Ly. ACS Chemical Biology (2013), 8(2), 345-352. DOI: 10.1021/cb3003946 High affinity γPNA sandwich hybridization assay for rapid detection of short nucleic acid targets with single mismatch discrimination. Johnathan M. Goldman, Li Ang Zhang, Arunava Manna, Bruce A. Armitage, Danith H. Ly, and James W. Schneider. Biomacromolecules (2013), 14(7), 2253-2261. DOI: 10.1021/bm400388a Twisted Cyanines: A Non-Planar Fluorogenic Dye with Superior Photostability and its Use in a Protein-Based Fluoromodule Shank, Nathaniel I.; Pham, Ha H.; Waggoner, Alan S.; Armitage, Bruce A. Journal of the American Chemical Society (2013), 135(1), 242-251. DOI: 10.1021/ja308629w A Variable Light Domain Fluorogen Activating Protein Homodimerizes To Activate Dimethylindole Red. Senutovitch, Nina; Stanfield, Robyn L.; Bhattacharyya, Shantanu; Rule, Gordon S.; Wilson, Ian A.; Armitage, Bruce A.; Waggoner, Alan S.; Berget, Peter B. Biochemistry (2012), 51(12), 2471-2485. DOI:10.1021/bi201422g Imaging of RNA in live cells. Armitage, Bruce A. Current Opinion in Chemical Biology (2011), 15(6), 806-812. DOI:10.1016/j.cbpa.2011.10.006 Wavelength Dependence of the Fluorescence Quenching Efficiency of Nearby Dyes by Gold Nanoclusters and Nanoparticles: The Roles of Spectral Overlap and Particle Size. Chowdhury, Sanchari; Wu, Zhikun; Jaquins-Gerstl, Andrea; Liu, Shengpeng; Dembska, Anna; Armitage, Bruce A.; Jin, Rongchao; Peteanu, Linda A. Journal of Physical Chemistry C (2011), 115(41), 20105-20112. DOI:10.1021/jp204836w Fluorescent DNA Nanotags Featuring Covalently Attached Intercalating Dyes: Synthesis, Antibody Conjugation, and Intracellular Imaging. Stadler, Andrea L.; Delos Santos, Junriz O.; Stensrud, Elizabeth S.; Dembska, Anna; Silva, Gloria L.; Liu, Shengpeng; Shank, Nathaniel I.; Kunttas-Tatli, Ezgi; Sobers, Courtney J.; Gramlich, Philipp M. E.; et al. Bioconjugate Chemistry (2011), 22(8), 1491-1502. DOI:10.1021/bc100485f Kinetic discrimination in recognition of DNA quadruplex targets by guanine-rich heteroquadruplex-forming PNA probes. Roy, Subhadeep; Zanotti, Kimberly J.; Murphy, Connor T.; Tanious, Farial A.; Wilson, W. David; Ly, Danith H.; Armitage, Bruce A. Chemical Communications (Cambridge, United Kingdom) (2011), 47(30), 8524-8526. DOI:10.1039/c1cc12805a Synthesis and Characterization of Conformationally Preorganized, (R)-Diethylene Glycol-Containing γ-Peptide Nucleic Acids with Superior Hybridization Properties and Water Solubility. Sahu, Bichismita; Sacui, Iulia; Rapireddy, Srinivas; Zanotti, Kimberly J.; Bahal, Raman; Armitage, Bruce A.; Ly, Danith H. Journal of Organic Chemistry (2011), 76(14), 5614-5627. DOI:10.1021/jo200482d Blue fluorescent dye-protein complexes based on fluorogenic cyanine dyes and single chain antibody fragments. Zanotti, Kimberly J.; Silva, Gloria L.; Creeger, Yehuda; Robertson, Kelly L.; Waggoner, Alan S.; Berget, Peter B.; Armitage, Bruce A. Organic & Biomolecular Chemistry (2011), 9(4), 1012-1020. DOI:10.1039/c0ob00444h Substituent Effects on the Assembly of Helical Cyanine Dye Aggregates in the Minor Groove of a DNA Template. Stadler, Andrea L.; Renikuntla, Babu Rao; Yaron, David; Fang, Adam S.; Armitage, Bruce A. Langmuir (2011), 27(4), 1472-1479. DOI:10.1021/la104329c Telomeric repeat mutagenicity in human somatic cells is modulated by repeat orientation and G-quadruplex stability. Damerla, Rama Rao; Knickelbein, Kelly E.; Kepchia, Devin; Jackson, Abbe; Armitage, Bruce A.; Eckert, Kristin A.;Opresko, Patricia L. DNA Repair (2010), 9(11), 1119-1129. DOI:10.1016/j.dnarep.2010.07.014 Loop and Backbone Modifications of Peptide Nucleic Acid Improve G-Quadruplex Binding Selectivity. Lusvarghi, Sabrina; Murphy, Connor T.; Roy, Subhadeep; Tanious, Farial A.; Sacui, Iulia; Wilson, W. David; Ly, Danith H.; Armitage, Bruce A. Journal of the American Chemical Society (2009), 131(51), 18415-18424. DOI:10.1021/ja907250j Enhanced Photostability of Genetically Encodable Fluoromodules Based on Fluorogenic Cyanine Dyes and a Promiscuous Protein Partner. Shank, Nathaniel I.; Zanotti, Kimberly J.; Lanni, Frederick; Berget, Peter B.; Armitage, Bruce A. Journal of the American Chemical Society (2009), 131(36), 12960-12969. DOI:10.1021/ja9016864 Peptide nucleic acids (PNAs). Achim, Catalina; Armitage, Bruce A.; Ly, Danith H.; Schneider, James W. Edited By: Begley, Tadhg P. Wiley Encyclopedia of Chemical Biology (2009), 3, 588-597. DOI:10.1002/9780470048672.wecb435 Refined multivalent display of bacterial spore-binding peptides. Lusvarghi, Sabrina; Kim, Jenny Morana; Creeger, Yehuda; Armitage, Bruce Alan. Organic & Biomolecular Chemistry (2009), 7(9), 1815-1820. DOI:10.1039/b820013k Cyanine dye-nucleic acid interactions. Armitage, Bruce A. Topics in Heterocyclic Chemistry (2008), 14(Heterocyclic Polymethine Dyes), 11-29. DOI:10.1007/7081_2007_109 Fluorescent DNA Nanotags Based on a Self-Assembled DNA Tetrahedron. Ozhalici-Unal, Hayriye; Armitage, Bruce A. ACS Nano (2009), 3(2), 425-433. DOI:10.1021/nn800727x Molecular engineering of torsional potentials in fluorogenic dyes via electronic substituent effects. Ediz, Volkan; Lee, Jihoon L.; Armitage, Bruce A.; Yaron, David. Journal of Physical Chemistry A (2008), 112(40), 9692-9701. DOI:10.1021/jp805546s