个人简介

2011–present Associate Professor of Chemistry and Biological Sciences, Carnegie Mellon University 2006–2011 Associate Research Professor of Chemistry, Carnegie Mellon University 1998–2006 Founder, Principal Scientist Quantum Dot Corporation 1995–1998 Ph.D. Physical Chemistry, University of California, Berkeley 1991–1995 B.S. Chemistry, Massachusetts Institute of Technology

研究领域

Bioorganic & Chemical Biology/Biophysical/Sensors/Probes & Imaging/Spectroscopy & Single Molecule Analysis

Biological research has been propelled by the availability of fluorescent proteins that allow dynamic microscopy of living cells. The repertoire of intrinsically fluorescent proteins is substantially less diverse in form and function than the repertoire of chemically synthetized dye molecules, yet genetic targeting provides such a significant advantage that probes 2-10-fold less bright than typical organic dyes are routinely used in fluorescence imaging. Our work is focused on developing tools that couple the best of the synthetic dyes with the advantages of genetic targeting. These novel probes allow unique investigations of cell-biological and biochemical processes fundamental to our understanding of health and diseases. New tools for single molecule investigations and superresolution imaging The limits of microscopy can be expanded dramatically by design and use of the right fluorescent dye molecules. Research in this area is focused on enhancing the brightness, stability and activation properties of dye molecules useful with our genetically expressed protein targets. We exploit these probes with sensitive fluorescence imaging to detect biological processes at higher resolution and longer timescales than conventionally achieved in fluorescence microscopy. These tools are applied to study the translation and folding of single molecules by the protein synthesis machinery of eukaryotic cells (the ribosome). Targeted tools for protein trafficking The endocytic/exocytic processes are fundamental to a wide range of biological phenomena, including immunity, allergy and synaptic transmission. Utilizing engineered proteins that fold well in the secretory pathway of cells and bind to otherwise weakly fluorescent dye molecules, we have developed a series of fluorescent indicators that are “activated by targeting.” These ratiometric dyes enable direct interrogation of the endocytic trafficking process and the protein fate after stimulation by biological ligands or drugs. Trafficking of receptors under the influence of genetic mutations and pharmacologic treatments provides new mechanistic and therapeutic insights into receptor action in these important biological processes.

近期论文

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Armitage BA. Analysis of PNA Hybridization by Surface Plasmon Resonance. Methods Mol Biol. 2014;1050:159-65. doi: 10.1007/978-1-62703-553-8_13. PubMed PMID: 24297358. Armitage BA. Formation and Characterization of PNA-Containing Heteroquadruplexes. Methods Mol Biol. 2014;1050:73-82. doi: 10.1007/978-1-62703-553-8_6. PubMed PMID: 24297351. Gallo E, Jarvik J. Fluorogen-Activating scFv Biosensors Target Surface Markers on Live Cells Via Streptavidin or Single-Chain Avidin. Molecular Biotechnology (2014), DOI:10.1007/s12033-014-9732-6. Gallo E, Vasilev KV, Jarvik J. Fluorogen-activating-proteins as universal affinity biosensors for immunodetection. Biotechnology and Bioengineering (2014), 111(3), 475-484. DOI:10.1002/bit.25127. Goldman JM, Zhang LA, Manna A, Armitage BA, Ly DH, Schneider JW. High affinity gPNA sandwich hybridization assay for rapid detection of short nucleic acid targets with single mismatch discrimination. Biomacromolecules (2013), 14(7), 2253-2261. DOI:10.1021/bm400388a. Gupta A, Lee L-L, Roy S, Tanious FA, Wilson WD, Ly DH, Armitage BA. Strand Invasion of DNA Quadruplexes by PNA: Comparison of Homologous and Complementary Hybridization. ChemBioChem (2013), 14(12):1476-1484. DOI:10.1002/cbic.201300263. Lan L, Nakajima S, Wei L, Sun L, Hsieh C-L, Sobol RW, Bruchez M, Van Houten B, Yasui A, Levine, AS. Novel method for site-specific induction of oxidative DNA damage reveals differences in recruitment of repair proteins to heterochromatin and euchromatin. Nucleic Acids Research (2014), 42(4), 2330-2345. DOI:10.1093/nar/gkt1233. Pastori C, Diomede L, Venuti A, Fisher G, Jarvik J, Bomsel M, Sanvito F, Lopalco L. Induction of HIV-blocking anti-CCR5 IgA in Peyers's patches without histopathological alterations. J Virol. 2014 Apr;88(7):3623-35. doi: 10.1128/JVI.03663-13. Epub 2014 Jan 8. PMID: 24403594. Patrick MJ, Janjic JM, Teng H, O'Hear MR, Brown CW, Stokum JA, Schmidt BF, Ahrens ET, Waggoner AS. Intracellular pH Measurements Using Perfluorocarbon Nanoemulsions. Journal of the American Chemical Society (2013), 135(49), 18445-18457. DOI:10.1021/ja407573m. Saunders MJ, Block E, Sorkin A, Waggoner AS, Bruchez, MP. A Bifunctional Converter: Fluorescein Quenching scFv/Fluorogen Activating Protein for Photostability and Improved Signal to Noise in Fluorescence Experiments. Bioconjugate Chemistry (2014), 25(8), 1556-1564. DOI:10.1021/bc500273n. Schneider JW, Goldman JM, Armitage BA, Ly DH. miRNA detection using alkylated g-PNAs and ultrabright flurorescent tags in capillary electrophoresis. 87th ACS Colloid and Surface Science Symposium, Riverside, CA, United States, June 23-26 (2013), COLLSYMP-66. Shank NI, Pham HH, Waggoner AS, Armitage BA. Twisted Cyanines: A Non-Planar Fluorogenic Dye with Superior Photostability and its Use in a Protein-Based Fluoromodule. Journal of the American Chemical Society (2013), 135(1), 242-251. DOI:10.1021/ja308629w. Tan C, Saurabh S, Bruchez MP, Schwartz R, Le Duc P. Reply to 'Complexity of molecular crowding in cell-free enzymatic reaction networks'. Nature Nanotechnology (2014), 9(6), 407-408. DOI:10.1038/nnano.2014.111. Tan X, Dey SK, Telmer C, Zhang X, Armitage BA, Bruchez MP. Aptamers Act as Activators for the Thrombin Mediated-Hydrolysis of Peptide Substrates. ChemBioChem (2014), 15(2), 205-208. DOI:10.1002/cbic.201300693. Thomas SM, Sahu B, Rapireddy S, Bahal R, Wheeler SE, Procopio EM, Kim J, Joyce SC, Contrucci S, Wang Y, et al. Antitumor Effects of EGFR Antisense Guanidine-Based Peptide Nucleic Acids in Cancer Models. ACS Chemical Biology (2013), 8(2), 345-352. DOI:10.1021/cb3003946. Wu Y, Tapia PH, Jarvik J, Waggoner AS, Sklar LA. Real-time detection of protein trafficking with high-throughput flow cytometry (HTFC) and fluorogen-activating protein (FAP) base biosensor. Curr Protoc Cytom. (2014) 67:Unit 9.43. doi: 10.1002/0471142956.cy0943s67. PMID: 24510772. Yan Q, Schwartz SL, Maji S, Huang F, Szent-Gyorgyi C, Lidke DS, Lidke KA, Bruchez MP. Localization Microscopy using Noncovalent Fluorogen Activation by Genetically Encoded Fluorogen-Activating Proteins. ChemPhysChem (2014), 15(4), 687-695. DOI:10.1002/cphc.201300757. Youker RT, Teng H. Measuring protein dynamics in live cells: protocols and practical considerations for fluorescence fluctuation microscopy. J. Biomed. Opt. (2014) 19(9):090801. DOI:10.1117/1.JBO.19.9.090801. Bachert C, Linstedt AD. A sensor of protein O-glycosylation based on sequential processing in the Golgi apparatus. Traffic. 2013 Jan;14(1):47-56. doi: 10.1111/tra.12019. Epub 2012 Oct 31. PubMed PMID: 23046148; PubMed Central PMCID: PMC3548014. Coelho LP, Kangas JD, Naik AW, Osuna-Highley E, Glory-Afshar E, Fuhrman M, Simha R, Berget PB, Jarvik JW, Murphy RF. Determining the subcellular location of new proteins from microscope images using local features. Bioinformatics. 2013 Sep 15;29(18):2343-9. doi: 10.1093/bioinformatics/btt392. Epub 2013 Jul 8. PubMed PMID: 23836142; PubMed Central PMCID: PMC3753569.