Updated: December 3, 2015
CBC Scholar: Class of 2011
PhD Candidate, Department of Chemistry (PSD), UChicago, Advisor: Chuan He
HE LAB WEBPAGE
On March 7, 2012, Fei successfully defended his thesis: "Exploring the Molecular Mechanism of Virulence Regulation in S. aureus and the Chemical Approach Targeting Its Pathogenesis." Fei moved to California in April, 2012 to postdoc with Prof. Frances Arnold at Caltech. Congratulations!
During the past year, my research has been focusing on the signaling mechanisms of human pathogen Staphylococcus aureus. Specifically, my work consists of three parts: 1) Characterization of molecular mechanism of the virulence two component system saeRS in S. aureus; 2) Identification of a novel S. aureus two component system airSR; 3) small molecule-mediated virulence suppression in S. aureus by targeting the global transcription regulator MgrA.
1) SaeRS: The two-component system is a paradigm of signal transduction in bacteria. The virulence two-component system SaeRS plays an essential role in the staphylococcal pathogenesis. My study disclosed the detailed molecular mechanism of this TCS. Using biochemical and bioinformatic tools, we identified the conserved DNA binding site of the response regulator SaeR. By comparing the growth of the sae mutant and the parental strain, we provided a plausible explanation for the frequent occurrence of sae mutation that haunts the staphylococcal study. Our current effort is focusing on developing inhibitors against SaeRS. A cell-based GFP reporter system for SaeRS has been constructed and will be exploited for future screening.
2) AirSR: We demonstrated that S. aureus two-component system AirSR is a master redox-reponsive regulatory system. We discovered that the sensor kinase AirS is an iron-sulfur cluster protein. By biochemical characterization and in vivo phenotypic studies, we firmly established the correlation between the redox-status of [2Fe-2S] and the regulatory function of AirSR.
3) MgrA: We established a fluorescence-anisotropy-based high-throughput screening assay in order to identify small molecules inhibiting MgrA. Approximately 10,000 compounds were screened and 100 hits were selected for further studies. A series of biochemical assays were carried out to confirm their ability to disrupt MgrA-DNA interactions. So far, two compounds were shown to be able to downregulate the virulence expression inside S. aureus. According to the mouse model of infections, one compound was capable of reducing S. aureus virulence by ten-fold.
Deng X, Weerapana E, Ulanovskaya O, Sun F, Liang H, Ji Q, Ye Y, Fu Y, Zhou L, Li J, Zhang H, Wang C, Alvarez S, Hicks LM, Lan L, Wu M, Cravatt BF, He C. Proteome-wide Quantification and Characterization of Oxidation-Sensitive Cysteines in Pathogenic Bacteria. Cell Host Microbe. 2013 Mar 13;13(3):358-70. (PubMed)
Ji Q, Zhang L, Jones MB, Sun F, Deng X, Liang H, Cho H, Brugarolas P, Gao YN, Peterson SN, Lan L, Bae T, He C. Molecular mechanism of quinone signaling mediated through S-quinonization of a YodB family repressor QsrR. Proc Natl Acad Sci U S A. 2013 Mar 26;110(13):5010-5. (PubMed)
Jeong DW, Cho H, Jones MB, Shatzkes K, Sun F, Ji Q, Liu Q, Peterson SN, He C, Bae T. The auxiliary protein complex SaePQ activates the phosphatase activity of sensor kinase SaeS in the SaeRS two-component system of Staphylococcus aureus. Mol Microbiol. 2012 Oct;86(2):331-48. (PubMed)
Sun F, Ding Y, Ji Q, Liang Z, Deng X, Wong CC, Yi C, Zhang L, Xie S, Alvarez S, Hicks LM, Luo C, Jiang H, Lan L, He C. Protein cysteine phosphorylation of SarA/MgrA family transcriptional regulators mediates bacterial virulence and antibiotic resistance. Proc Natl Acad Sci U S A. 2012 Sep 18;109(38):15461-6. (PubMed)
Sun F, Liang H, Kong X, Xie S, Cho H, Deng X, Ji Q, Zhang H, Alvarez S, Hicks LM, Bae T, Luo C, Jiang H, He C. Quorum-sensing agr mediates bacterial oxidation response via an intramolecular disulfide redox switch in the response regulator AgrA. Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):9095-100. (PubMed)
Ji Q, Zhang L, Sun F, Deng X, Liang H, Bae T, He C. Staphylococcus aureus CymR is a new thiol-based oxidation-sensing regulator of stress resistance and oxidative response. J Biol Chem. 2012 Jun 15;287(25):21102-9. (PubMed)
Liang H, Deng X, Ji Q, Sun F, Shen T, He C. Pseudomonas aeruginosa global regulator VqsR directly inhibits QscR to control quorum-sensing and virulence gene expression. J Bacteriol. 2012 Jun;194(12):3098-108. (PubMed)
Deng X, Sun F, Ji Q, Liang H, Missiakas D, Lan L, He C. Expression of multidrug resistance efflux pump gene norA is iron-responsive in Staphylococcus aureus. J Bacteriol. 2012 Apr;194(7):1753-62. (PubMed)
Sun F, Ji Q, Jones MB, Deng X, Liang H, Frank B, Telser J, Peterson SN, Bae T, He C. AirSR, a [2Fe-2S] Cluster-Containing Two-Component System, Mediates Global Oxygen Sensing and Redox Signaling in Staphylococcus aureus. J Am Chem Soc. 2012 Jan 11;134(1):305-14. (PubMed)
Sun F, Zhou L, Zhao BC, Deng X, Cho H, Yi C, Jian X, Song CX, Luan CH, Bae T, Li Z, He C. Targeting MgrA-mediated virulence regulation in Staphylococcus aureus. Chem Biol. 2011 Aug 26;18(8):1032-41. (PubMed)
Sun F, Cho H, Jeong DW, Li C, He C, Bae T. Aureusimines in Staphylococcus aureus are not involved in virulence. PLoS One. 2010 Dec 29;5(12):e15703. (PubMed)
Wegner SV, Sun F, Hernandez N, He C. The tightly regulated copper window in yeast. Chem Commun (Camb). 2011 Mar 7;47(9):2571-3. (PubMed)
Li C*, Sun F*, Cho H, Yelavarthi V, Sohn C, He C, Schneewind O, Bae T.CcpA mediates proline auxotrophy and is required for Staphylococcus aureus pathogenesis. J Bacteriol. 2010 Aug;192(15):3883-92. (*Co-first author.) (PubMed)
Sun F, Li C, Jeong D, Sohn C, He C, Bae T. In the Staphylococcus aureus two-component system sae, the response regulator SaeR binds to a direct repeat sequence and DNA binding requires phosphorylation by the sensor kinase SaeS. J Bacteriol. 2010 Apr;192(8):2111-27. (PubMed)
- CBC Scholar 2011-2012
- The Everett E Gilbert Memorial Prize, Spring 2010