(1) Chemoproteomics: To expand landscape of the thiol redox proteome
The nucleophilic thiol group allows cysteines to undergo a broad range of redox modifications. Emerging evidence suggests that these modifications are important in cellular redox regulation and protection against oxidative damage. Identification of protein targets of thiol redox modifications is crucial to understanding of their roles in biology and disease. Our research programs develop several chemoproteomic technologies to investigate protein targets of thiol redox modifications, including total cysteine oxidation, S-sulfenylation, etc., in complex proteomes. These studies not only expand the landscape of thiol redox modifications, but also suggest novel redox mechanisms of several proteins with key biological functions.
(2) Redox-based signal transduction
Redox-based modification of protein thiols by exogenous and endogenous oxidant is a crucial mechanism in cell signaling. We are therefore interested in studying molecular mechanisms underlying cysteine-mediated protein functions in cell signaling under oxidative perturbation. Our research programs will employ multidisciplinary research tools in chemical biology, biochemistry, and structure biology to define key proteins that control redox sensing and to interrogate how cellular redox sensors transduce redox signals into the downstream effects. Our group is also interested in studying dysregulated redox signaling in a range of human diseases, including neurodegenerative diseases, inflammation, and cancer. For instance, one of our research programs is toward understanding how thiol redox modification of proteins regulates signaling networks underlying oncogene-mediated tumorigenesis, which has been linked to aberrant redox status.
(3) Target engagement of natural products
Natural products have been a rich source of compounds for drug discovery and chemical biology. My group will employ natural products as chemical genetics tools to gain insight into how these molecules affect signaling pathways and protein regulation and to gain a deeper insight into their mechanism of actions. Our current research focuses on the global target profiling of natural products using the chemoproteomic platform we developed recently. This platform is also suitable for the target identification of synthetic small molecules and drugs.
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2、Yang J; Tallman KA; Porter NA; Liebler DC*. Quantitative chemoproteomics for site-specific analysis of protein alkylation by 4-hydroxy-2-nonenal in cells. Anal Chem. 2015. 87: 2535-2541
3、Yang J; Gupta V; Carroll KS; Liebler DC*. Site-specific mapping and quantification of protein S-sulphenylation in cells. Nat Commun. 2014, 5: 4776.
4、Yang J; Li CL; Ding L*; Guo QL*; You QD; Jin SH. Gambogic acid deactivates cytosolic and mitochondrial thioredoxins by covalent binding the functional domain. J Nat Prod.2012, 75: 1108-16
5、Yang J; Ding L*; Hu LL; Jin SH; Liu WY; You QD; Guo QL. Rapid characterization of caged xanthones in the resin of Garcinia hanburyi using multiple mass spectrometric scanning modes: the importance of biosynthetic knowledge based prediction. J Pharm Biomed Anal.2012, 60: 71-79
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7、Yang J; Ding L*; Hu LL; Jin SH; Liu WY; Wang ZZ; Xiao W; You QD; Guo QL. Comparison of electron capture-atmospheric pressure chemical ionization and electrospray ionization for the analysis of gambogic acid and its main circulating metabolite in dog plasma. Eur J Mass Spectrom. 2010, 16: 605-17
8、Yang J; Ding L*; Jin SH*; Liu XX; Liu WY; Wang ZZ. Identification and quantitative determination of a major circulating metabolite of gambogic acid in human. J Chromatogr B Analyt Technol Biomed Life Sci. 2010, 878: 659-66
9、Wu Y; Yang J; Ding L*; Xu GL; Qian WJ; Yun CH; He JC. Identification of the metabolites of ecabet bismuth in rat bile by liquid chromatography-electrospray ionization-tandem mass spectrometry. Eur J Mass Spectrom. 2009, 15: 531-9