CHEMICAL BIOLOGY

REDOX IMAGING, PROTEOMICS, AND OPTOGENETICS

Traditional methods for sensing rely on static lock-and-key binding approaches, which are difficult to apply to reactive, transient small molecules in complex biological settings. We are synthesizing small-molecule fluorescent, MRI, and PET imaging probes that exploit chemoselective, bioorthogonal chemistries to report on specific analytes in living cells and animals, with particular interest in the redox biology of reactive oxygen, sulfur, and carbonyl species. We are also developing new bioconjugation reactions for chemoproteomics as well as small-molecule inhibitor and antibody-drug conjugate therapeutics. Finally, we are creating optogenetic tools for controlling redox signals that govern information transfer in neural circuits in live-cell culture and mouse models.


REVIEWS

Bruemmer, K. J.*; Brewer, T. F.*; Chang, C. J. "Fluorescent probes for imaging formaldehyde in biological systems", Curr. Opin. Chem. Biol. 2017, 39, 17-23. [html] [pdf]




Brewer, T. F.; Garcia, F. J.; Onak, C. S.; Carroll, K. S.; Chang, C. J. "Chemical Approaches to Discovery and Study of Sources and Targets of Hydrogen Peroxide Redox Signaling Through NADPH Oxidase Proteins", Annu. Rev. Biochem. 2015, 84, 765-790. [html] [pdf] [Chemical & Engineering News Story]




Lin, V. S.; Chen, W.; Xian, M.; Chang, C. J. "Chemical probes for molecular imaging and detection of hydrogen sulfide and reactive sulfur species in biological systems", Chem. Soc. Rev. 2015, 44, 4596-4618. [pdf] [html]




Chan, J.; Dodani, S. C.; Chang, C. J. "Reaction-based small-molecule fluorescent probes for chemoselective bioimaging", Nat. Chem. 2012, 4, 973-984. [pdf] [html]




Lippert, A. R.; Van de Bittner, G. C.; Chang, C. J. "Boronate Oxidation as a Bioorthogonal Reaction Approach for Studying the Chemistry of Hydrogen Peroxide in Living Systems", Acc. Chem. Res. 2011, 44, 793-804. [pdf] [html]




Dickinson, B. C.; Chang, C. J. "Chemistry and biology of reactive oxygen species in signaling or stress responses", Nat. Chem. Biol. 2011, 7, 504-511. [pdf] [html]





FLUORESCENT PROBES AND CELL BIOLOGY

Bruemmer, K. J.*; Walvoord, R. R.*; Brewer, T. F.; Burgos-Barragan, G.; Wit, N.; Pontel, L. B.; Patel, K. J.; Chang, C. J. "Development of a General Aza-Cope Reaction Trigger Applied to Fluorescence Imaging of Formaldehyde in Living Cells", J. Am. Chem. Soc. 2017, 139, 5338-5350. [html] [pdf]




Brewer, T. F.; Chang, C. J. "An Aza-Cope Reactivity-Based Fluorescent Probe for Imaging Formaldehyde in Living Cells", J. Am. Chem. Soc. 2015, 37, 10886–10889. [html] [pdf]




Lin, V. S.; Lippert, A. R.; Chang, C. J. "Cell-trappable Fluorescent Probes for Endogenous Hydrogen Sulfide Signaling and Imaging H2O2-Dependent H2S Production", Proc. Natl. Acad. Sci. USA 2013, 110, 7131-7135. [pdf] [html] [C&E News] [CRT Spotlight] [Faculty of 1000 Recommendation]




Michel, B. W.; Lippert, A. R.; Chang, C. J. "A Reaction-Based Fluorescent Probe for Selective Imaging of Carbon Monoxide in Living Cells Using a Palladium-Mediated Carbonylation", J. Am. Chem. Soc. 2012, 134, 15668-15671. [pdf] [html] [C&E News]




Dickinson, B. C., Peltier, J., Stone, D., Schaffer, D. V., Chang, C. J. "Nox2 redox signaling maintains essential cell populations in the brain", Nat. Chem. Biol. 2011, 7, 106-112. [pdf] [html]





CHEMOPROTEOMICS

Lin, S.; Yang, X.; Jia, S.; Weeks, A. M.; Hornsby, M.; Lee, P. S.; Nichiporuk, R. V.; Iavarone, A. T.; Wells, J. A.; Toste, F. D.; Chang, C. J. "Redox-based reagents for chemoselective methionine bioconjugation", Science 2017, 355, 597-602. [html] [pdf] [C&E News] [Berkeley Lab] [Phys. Org] [In the Pipeline] [ACS Chem. Biol.]





BIOLUMINESCENT, MRI, AND PET PROBES

Liu, W.; Truillet, C.; Flavell, R. R.; Brewer, T. F.; Evans, M. J.; Wilson, D. M.; Chang, C. J. "A reactivity-based [18F]FDG probe for in vivo formaldehyde imaging using positron emission tomography", Chem. Sci. 2016, 7, 5503-5507. [html] [pdf]




Carroll, V.; Michel, B. W.; Blecha, J.; VanBrocklin, H.; Keshari, K.; Wilson, D.; Chang, C. J. "A Boronate-Caged [18F]FLT Probe for Hydrogen Peroxide Detection Using Positron Emission Tomography", J. Am. Chem. Soc. 2014, 136, 14742-14745. [html] [pdf]




Van de Bittner, G. C.; Bertozzi, C. R.; Chang, C. J. "Strategy for Dual-Analyte Luciferin Imaging: In Vivo Bioluminescence Detection of Hydrogen Peroxide and Caspase Activity in a Murine Model of Acute Inflammation", J. Am. Chem. Soc. 2013, 135, 1783-1795. [pdf] [html]




Lippert, A. R.; Keshari, K. R.; Kurhanewicz, J.; Chang, C. J. "A Hydrogen Peroxide-Responsive Hyperpolarized 13C MRI Contrast Agent", J. Am. Chem. Soc. 2011, 133, 3776-3779. [pdf] [html]







BACK TO TOP


Updated 29 May 2017