Associate Professor of Biological Sciences and Chemistry; Director, Molecular Biosensor and Imaging Center; Associate Professor of Biomedical Engineering (Courtesy)
Carnegie Mellon University
Phone: (412) 268-9661
Fax: (412) 268-6571
Office: Mellon Institute 294A
Lab: Mellon Institute 160
Associate Professor of Biological Sciences and Chemistry and Director, Molecular Biosensor and Imaging Center
fluorescence, biological microscopy, imaging, light-harvesting structures, biosensors, single molecule biophysics, protein translation, protein folding, protein trafficking
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.
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).
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.
|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|
|2006||Rank Prize Optoelectronics Award|
|2004||Honoree “Top 100 Young Innovators” Technology Review Magazine|
|2004||R&D 100 Award for Innovative Products based on Qdot Conjugate technology|
|2003||Science Magazine Top Ten Scientific Innovations of 2003 — “Quantum dots for biological detection”|
|1995||National Science Foundation Graduate Research Fellowship|
Grover, A., Schmidt, B. F., Salter, R. D., Watkins, S. C., Waggoner, A. S., & Bruchez, M. P. (2012). Genetically Encoded pH Sensor for Tracking Surface Proteins through Endocytosis. Angewandte Chemie (International Ed in English), 51(20), 4838–4842. doi:10.1002/anie.201108107
Shruti, S., Urban-Ciecko, J., Fitzpatrick, J. A., Brenner, R., Bruchez, M. P., & Barth, A. L. (2012). The Brain-Specific Beta4 Subunit Downregulates BK Channel Cell Surface Expression. PLoS ONE, 7(3), e33429. doi:10.1371/journal.pone.0033429
Yushchenko, D. A., Zhang, M., Yan, Q., Waggoner, A. S., & Bruchez, M. P. (2012). Genetically targetable and color-switching fluorescent probe. Chembiochem : a European Journal of Chemical Biology, 13(11), 1564–1568. doi:10.1002/cbic.201200334
Szent-Gyorgyi C, Schmidt BF, Fitzpatrick, JAJ and Bruchez, MP. Fluorogenic Dyedrons with Multiple Donor Chromophores as Bright Genetically Targeted and Activated Probes. Journal of the American Chemical Society. (2010) [.pdf]
Fisher GW, Adler SA, Fuhrman MH, Waggoner AS, Bruchez MP, and Jarvik JW. Detection and Quantification of β2AR Internalization in Living Cells using FAP-based Biosensors. Journal of Biomolecular Screening 2010.
Fitzpatrick JAJ, Yan Q, Sieber JJ, Dyba M, Schwarz U, Szent-Gyorgyi C, Woolford C, Berget PB, Waggoner AS and Bruchez MP. STED nanoscopy in living cells using Fluorogen Activating Peptides. Bioconjugate Chemistry 2009. [.pdf]
Fitzpatrick JAJ, Andreko SK, Ernst LA, Waggoner AS, Ballou B and Bruchez MP. Long term persistence and spectral blue-shifting of quantum dots in vivo. Nano Letters 2009. [.pdf]
Szent-Gyorgyi, C., Schmidt, B., Creeger, Y., Fisher, G., Zakel, K., Adler, S., Fitzpatrick, J., Woolford, C., Yan,, Q., Vasilev, K., Berget, P.B., Bruchez, M.P., Jarvik, J. and Waggoner, A.S.. Fluorogen activating proteins: Technology for imaging and assaying cell surface proteins. Nature Biotechnol 2008. [.pdf]