1) Type III secretion system (T3SS) of Pseudomonas aeruginosa:
Regulation of the T3SS and host responses to the T3SS injected bacterial toxins.
2) Bacterial resistance to antibiotics:
Understanding mechanisms of antibiotic resistance and develop strategies to counter the resistance.
3) Bacteria mediated delivery of target proteins into mammalian cells:Use bacterial T3SS as a tool to deliver proteins of interest into mammalian cells for various purposes.
Pseudomonas aeruginosa causes a wide range of infections, from minor skin infections to serious and sometimes life-threatening complications. P. aeruginosa is a causative agent of systemic infections in immunocompromised patients such as those receiving chemotherapy, elderly patients and burn victims. In special groups of patients, P. aeruginosa can also cause localized infections, particularly in the lungs of cystic fibrosis patients and corneas of certain contact lens users.
Type III secretion system (T3SS) is encoded by various animal and plant pathogens. It encodes over 30 proteins that assemble into a “needle” complex designed to deliver bacterial proteins directly into the cytoplasmic compartment of eukaryotic cells. In animal pathogens, the principle function of T3SS is to deliver anti-host-virulence-determinants into mammalian cells, for their survival in host environment.
(i) Regulation. The T3SS of P. aeruginosa responds to various environmental signals such as low calcium, direct contact with mammalian cells and various environmental stresses. We are interested in understanding the mechanism by which the T3SS genes are regulated during various stages of host infections.
(ii) T3SS induced apoptosis. There are five known effector molecules that are secreted by the T3SS of P. aeruginosa, including ExoS, ExoT, ExoY, ExoU and NDK. These toxins possess various enzymatic activities to influence physiology of host cells. We intend to understand the mechanisms by which the translocated bacterial proteins intoxicate the host cells and elucidate relevant signaling pathways.
(iii) Applications. The T3SS has been adopted to delivery proteins of interests into mammalian cells. Those successfully delivered proteins include cytoplasmic and nuclear proteins. Utility of the system includes cellular reprogramming via injection of transcriptional factors, genome editing via TALEN nuclease delivery, targeted vaccine delivery to trigger cell-mediated immunity, and tumor cell specific delivery for cancer therapy. Achieving all of these in a clinically safe manner is our ultimate goal.
Bacterial resistance to antibiotics poses a major threat to human health. We are interested in understanding the various mechanisms of antibiotic resistance and develop strategies to counter bacterial resistance, i.e. identifying chemical inhibitors for the key components of the bacterial resistance. For instance, we have discovered that a two-component regulatory system in P. aeruginosa can regulate the bacterial membrane permeability. We intend to understand the molecular details of the membrane permeability control and identify chemicals that increase membrane permeability. We propose to combat and limit the development of antibiotic resistance by combined use of permeability-enhancing chemicals with antibiotics.
Publications (selected from 2013-2016):
- Bichsel, C., D. Neeld, T. Hamazaki, L. Chang, L. Yang, N. Terada and S. Jin. (2013) Trans-differentiation of Fibroblasts to Myocytes via Bacterial Injection of MyoD Protein. Cell Reprogram 15(2):117-25.
- Li, K., C. Xu, Y. Jin, Z. Sun, C. Liu, J. Shi, G. Chen, R. Chen, S. Jin, W. Wu. (2013) SuhB is a regulator of multiple virulence genes and essential for pathogenesis of Pseudomonas aeruginosa. mBio 4(6):e00419-13.
- Jia J, Y. Jin, T. Bian, D. Wu, L. Yang, N. Terada, W. Wu and S. Jin. (2014) Bacterial delivery of TALEN proteins for human genome editing. PLoS One 9(3):e91547.
- Neeld, D., Y. Jin, C. Bichsel, J. Jia, J. Guo, F. Bai, W. Wu, U-H. Ha, N. Terada and S. Jin. (2014) Pseudomonas aeruginosa injects NDK into host cells through a type III secretion system. Microbiol 160:1417-26.
- Jia, J., F. Bai, Y. Jin, K. E. Sanstefano, U. Ha, D. Wu, W. Wu, N. Terada and S. Jin. (2015) Efficient gee editing in pluripotent stem cells by bacterial injection of TALEN proteins. Stem Cells Translational Medicine 4: 1-14.
- Xia, G., Y. Gao, S. Jin, S.H. Subramony, N. Terada, L. P. W. Ranum, M. S. Swanson and T. Ashizawa. (2015) Genome Modification Leads to Phenotype Reversal in Human Myotonic Dystrophy Type 1 Induced Pluripotent Stem Cell-Derived Neural Stem Cells. Stem Cells 33(6):1829-38.
- Bai, F., J. Jia, C. Lim, K. Santostefano, C. Simmons, N. Terada and S. Jin. (2015) Directed differentiation of embryonic stem cells into cardiomyocytes by bacterial injection of transcriptional factors. Sci Report 5:15014.
- Shi, J., Y. Jin, T. Bian, K. Li, Z. Sun, Z. Cheng, S. Jin and W. Wu. (2015) A Novel Ribosome Associated Protein SuhB Regulates Expression of MexXY through Translational Control of PA5471 Leader Peptide in Pseudomonas aeruginosa. Mol Micro 98(2):370-83.
- Guo Q, Wei Y, Xia B, Jin Y, Liu C, Pan X, Shi J, Zhu F, Li J, Qian L, Liu X, Cheng Z, Jin S, Lin J, Wu W. (2016) Identification of a small molecule that simultaneously suppresses virulence and antibiotic resistance of Pseudomonas aeruginosa. Sci Rep 6:19141.
- Tan H, Zhang L, Weng Y, Chen R, Zhu F, Jin Y, Cheng Z, Jin S, Wu W. (2016) PA3297 Counters Antimicrobial Effect of Azithromycin in Pseudomonas aeruginosa. Frontiers in Microbiology 7:317.
Office: ARB R1-293
Phone: (352) 273-5973
Postdoctoral Fellow, University of Washington
Ph.D., University of Washington
M.S., University of Washington
B.S., Nankai University
Awards, Professional Service:
1985-86 World Bank Graduate Student Fellowship.
1988-90 PMIF Predoctoral Fellowship, University of Washington, Seattle, WA.
1996 Junior Faculty Excellence Award, Oak Ridge Associated Universities.
1996 Fist Award, National Institute of Health.
1997 Career Development Award, National Science Foundation.
1998 Charles C. Randall Award, SC Branch of American Society for Microbiology.
2000 Berbecker Scholarship Award, Cystic Fibrosis Foundation.
2001 Research Scholar Award, American Cancer Society.
2000-2003 Member, MBC study section of American Cancer Society.
2002-2004 Member, Microbial Genetics Panel, National Science Foundation.
2005-present Adhoc reviewer for various funding agencies, including NIH study section (BACP, HIBP, ZHL1 CCT-X and CF Translational Core Center), CFF, NSFC and ASTAR etc.
A. Medical Student Teaching:
B. Graduate Student Teaching:
Advanced Microbial Genetics
Special topics on Microbiology and Immunology
Stem Cell Biology