Carroll, Kate - The Scripps Research Institute

研究领域

The goal of our research is to understand molecular mechanisms of redox-based regulation of protein function and the regulation by redox systems of complex physiological processes. To achieve these goals, we develop and apply new technologies that cut across the traditional boundaries of chemical and biological sciences. Chemical Tools to Map Redox Signaling Pathways Oxidative thiol modifications have emerged as a central mechanism for dynamic post-translational regulation of all major protein classes and correlate with many disease states. We focus on the development and application of chemoselective probes as tools to profile these modifications in cell-based systems and to identify biomarkers of oxidative stress. Thiolproteomic Technologies New methods for comprehensive and quantitative analysis of the "thiol" proteome are being developed and applied to the discovery of cellular signaling networks and regulatory mechanisms that involve oxidation of protein cysteine residues. Redox-Dependent Kinase and Phosphatase Inhibitors Our lab is taking a rational design approach toward the development irreversible, small-molecule inhibitors that target the oxidized forms of functionally important cysteine residues in kinases and phosphatases. Microbial Sulfur Metabolism Projects in this area focus on pathways of sulfur metabolism in human pathogens, such as Mycobacterium tuberculosis and the study of enzymes that are critical for virulence and survival using a range of chemical, biochemical, structural, and computational techniques.

近期论文

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Lo Conte, M.; Carroll, K. S. "The Redox Biochemistry of Protein Sulfenylation and Sulfinylation." J. Biol. Chem. 2013, 288(37):26480-8. [pdf] Paritala, H.; Carroll, K.S. "New Targets and Inhibitors of Mycobacterial Sulfur Metabolism." Infect Disord Drug Targets 2013, Apr;13(2):85-115 [pdf] Gupta, V.; Carroll, K. S. "Sulfenic Acid Chemistry, Detection and Cellular Lifetime". BBA - General Subjects. 2013, 1840(2), 847-75 [pdf] Truong, T. H.; Carroll, K. S. "Redox regulation of protein kinases". Crit. Rev. Biochem. Mol. 2013, 48(4), 332-56 [pdf] Pan, J.; Carroll, K. S. "Chemical Biology Approaches to Study Protein Cysteine Sulfenylation." Biopolymers. 2013, just accepted [pdf] Paulsen, C. E.; Carroll, K. S. “Cysteine-based redox signaling: Chemistry, biology, and tools for discovery.” Chem. Rev. 2013, 113(7), 4633-79. [pdf] Truong, T. H.; Carroll, K. S. "Redox-regulation of EGFR signaling through cysteine oxidation." Biochemistry. 2012, 51(50), 9954-65. [pdf] Lo Conte, M.; Carroll, K. S. "The chemistry of thiol oxidation and detection." Oxidative stress and redox regulation. Jakob, U. Ed.; Springer: New York 2012, Chapter 1. [pdf] Leonard, S. E.; Carroll, K. S. “Chemical ‘omics’ approaches for understanding protein cysteine oxidation in biology.” Curr. Opin. Chem. Biol. 2011, 15(1), 88-102. [pdf] Carroll, K. S. “Metabolite imaging: knock, nox-ROS there?” Nat. Chem. Biol. 2011, 7(2), 71-2. [pdf] Paulsen, C. E.; Carroll, K. S. “Orchestrating redox signaling networks through regulatory cysteine switches.” ACS Chem. Biol. 2010, 5(1), 47-62. [pdf] Reddie, K. G.; Carroll, K. S. “Expanding the functional diversity of proteins through cysteine oxidation.” Curr. Opin. Chem. Biol. 2008, 12(6), 746-54. [pdf] Bhave, D. P.; Muse, W. B. 3rd; Carroll, K. S. “Drug targets in mycobacterial sulfur metabolism.” Infect. Disord. Drug Targets. 2007, 7(2), 140-58. [pdf] Yang, J.; Gupta, V.; Carroll, K.S.; Liebler, D.C. "Site-specific mapping and quantification of protein S-sulphenylation in cells." Nat Commun. 2014 Sep 1;5:4776. [pdf] Garcia, F.J.; Carroll, K.S. "Redox-based probes as tools to monitor oxidized protein tyrosine phosphatases in living cells." Eur J Med Chem. 2014, in press [pdf] Martínez-Acedo, P.; Gupta, V.; Carroll, K.S. "Proteomic analysis of peptides tagged with dimedone and related probes." J. Mass Spectrom. 2014, 49(4), 257-65 [pdf] Bhaskar, A.; Chawla, M.; Mehta, M.; Parikh, P.; Chandra, P.; Bhave, D.; Kumar, D.; Carroll, K.S.; Singh, A. "Reengineering redox sensitive GFP to measure mycothiol redox potential of Mycobacterium tuberculosis during infection." PLoS Pathog. 2014, 10(1), e1003902. [pdf] Zhang, D.; Macinkovic, I.; Devarie-Baez, N.O.; Pan, J.; Park, C.M.; Carroll, K.S.; Filipovic, MR..; Xian, M. "Detection of Protein S-Sulfhydration by a Tag-Switch Technique." Angew. Chem. Int. Ed. Engl. 2014, 53(2), 575-81. [pdf] Paritala, H.; Carroll, K.S. "A Continuous Spectrophotometric Assay for APS Reductase Activity with Sulfite-Selective Probes." Anal. Biochem. 2013, 440(1), 32-9 [pdf] Pan, J.; Carroll, K. S. "Persulfide Reactivity in the Detection of Protein S-Sulfhydration." ACS Chem. Biol. 2013, just accepted manuscript [pdf]