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Jean-San Chia Professor

Tel:886-2-23123456 ext 67716
Email:chiajs@ntu.edu.tw


Experiences

BDS, National Taiwan University, 1980
MS, National Taiwan University, 1991
PhD, National Taiwan University, 1993

Professional specialties

Oral Microbiology & Immunology

Main Research Interests

Research Summary:
Work in my laboratory is focused on three major research programs: immunopathogenesis, host-commensal and pathogen interactions, and cancer immunology.

The objective of the immunopathogenesis program is to investigate the molecular mechanisms by which bacterial pathogens induce septic thromobosis and inflammation. Our pioneering works prove that commensal streptococci can evade efficiently the host innate immune surveillance and become heart pathogens to induce infective endocarditis (IE). IE is characterized by the formation of septic thrombus called vegetation with embedded pathogens like viridans streptococci forming biofilms. We are the first to elucidate the underlying mechanism and host factors contributing directly to the vegetation formation. Using a rat endocarditis model, we demonstrated that IE-inducing pathogens like S. mutans or S. godornii could hijack host immune effectors including anti-bacteria specific IgG and platelets to protect phagocytosis and to form biofilm in situ at damaged heart valves. We further indicate that these streptococci-platelet aggregates could further induce neutrophil extracellular traps (NETs) formation providing the framework for entrapping the streptococci-platelet aggregates into well-organized biofilm as well as for activating coagulation system to expand the size of vegetation (upper left panel; Circulation. 2015;131:571-81). These findings provide sound rationale to support the prophylactic prescription of anti-platelet agents like aspirin in addition to antibiotics to patients at high risk of endocarditis. We are now investigating the mechanisms that orchestrate the commensal-induced thrombosis and their role in autoimmune diseases.

The second research program in my laboratory is centered on the study of host-commensal and pathogen interactions. Human intestinal tract and oral cavity are occupied by more than thousand Mega commensal microflora, which are potential or “silent” opportunistic pathogens capable of inducing lethal infections or are associated with obesity, autoimmunity, or other chronic inflammatory diseases. However, how commensal microflora become pathogens and trigger systemic diseases are largely unknown. Specifically, we investigate strategies used by commensal Streptococci to from biofilms and to induce inflammatory responses in vivo. Using S. mutans as an example, we have uncovered a novel mechanism by which this pathogen sabotages host defense mechanisms. S. mutans tricks the host’s anti-bacterial IgG and platelets into synthesizing and forming the biofilm at the injured heart valves (left panel; J Infect Dis. 2012; 205: 1066-75). The S. mutans biofilm is a well-organized architecture composed of bacterial secreted matrix and extracellular DNA, the releasing or secreting of which are under coordinated control through the bacterial two component systems. We also found that ionized or bound calcium is a ‘host signature’ molecule (Mol Microbiol. 2009; 74:888-902.) that is sensed by the bacterial two component systems to induce an adaptive response to evade efficiently the neutrophil killing by binding to soluble fibronectin through bacterial autolysin AtlA. These novel discoveries unveils a new paradigm in the field of commensal bacterial pathogenesis and opens the door to novel investigation on the tactics used by commensal bacteria to promote disease. 

The third research program in my laboratory is focused on oral cancer biology and anti-tumor immune responses. My original interest in this field of study was cultivated by the observation that human oral cancer habors specific CD8+ effector memory T cell subsets and IL-17 producing Foxp3+ Treg cells associated with the progression and prognosis of oral cancer patients (left panel; Head Neck. 2011; 33: 1301-8; PLoS One. 2014 23:e85521). We have developed novel approaches to identify the tumor associated antigens of human oral cancer as well as the T cell polyfunctionality, exhaustion, and anergy. We are also collaborating with the clinical oncology department and Genomic Center of NTUMC to investigate and analyze the TCR repertoire of the tumor reactive CD8+ and Treg cells. These approaches will be helpful to establish the platform and clinical data bases for identifying antibody- and cell-mediated protective immune responses against oral or head and neck cancer. The ultimate goal of this work is to develop new and robust class of immune activators designed as an adjuvant to chemotherapeutics for oral cancers.

     

Selected Publications

  1. Yeh C. Y., Shun C. T., Kuo Y. M., Jung C. J., Hsieh S. C., Chiu Y. L., Chen J. W., Hsu R. B., Yang C. J., Chia J. S. 2015 Activated human valvular interstitial cells sustain IL-17 production to recruit neutrophils in infective endocarditis.Infect Immun. 2015 Mar 16. pii: IAI.02965-14. [Epub ahead of print] (NSC grant acknowledged, NSC 101-2321-B-002-055, NSC102-2321-B-002-010, and 103-2320-B-002-037-MY3), Ministry of Science and Technology (MOST 103-2321-B-002-024)
  2. Jung C. J., Yeh C. Y., Hsu R. B., Lee C. M., Shun C. T., Chia J. S. 2015 Endocarditis pathogen promotes vegetation formation by inducing intravascular neutrophil extracellular traps through activated platelets. Circulation. 2015 Feb 10; 131(6):571-81. doi: 10.1161/CIRCULATIONAHA.114.011432. Epub 2014 Dec 19. (NSC grant acknowledged, NSC 102-2321-B-002-010, 102-2321-B-002-055, MOST 103-2321-B-002-024 and 103-2320-B-002-037-MY3).
  3. Yeh C. Y., Jung C. J., Huang C. N., Huang Y. C., Lien H. T., Wang W. B., Wang L. F., Chia J. S. 2014 A legume product fermented by Saccharomyces cerevisiae modulates cutaneous atopic dermatitis-like inflammation in mice. BMC Complement Altern Med. 2014 Jun 18; 14:194. doi: 10.1186/1472-6882-14-194. (NSC grant acknowledged, NSC 101-2321-B-002-074 and NSC 101-2321-B-002-016)
  4. Lee JJ, Yeh CY, Jung CJ, Chen CW, Du MK, Yu HM, Yang CJ, Lin HY, Sun A, Ko JY, Cheng SJ, Chang YL and Chia JS (2014). Skewed Distribution of IL-7 Receptor-alpha-Expressing Effector Memory CD8(+) T Cells with Distinct Functional Characteristics in Oral Squamous Cell Carcinoma. Plos One 9. (SCI)
  5. Yeh C. Y., Yeh T. H., Jung C. J., Chen P. L., Lien H. T., Chia J. S. 2013 Activated human nasal epithelial cells modulate specific antibody response against bacterial or viral antigens. PLoS One 8:e55472. (NSC grant acknowledged, NSC 100-2314-B-002-044, NSC 101-2321-B-002-074 and NSC 101-2321-B-002-016).
  6. Jung C. J., Yeh C.Y., Shun C.T., Hsu R.B., Cheng H.W., Lin C.S., Chia J. S. 2012 Platelets enhance biofilm formation and resistance of endocarditis-inducing streptococci on the injured heart valve. J InfectDis.205:1066-75. (NSC grant acknowledged, NSC 98-2320-B002-047-MY3, 100-2321-B002-043, and  99-2314-B002-125-MY2)
  7. Lee JJ, Chang YL, Lai WL, Ko JY, Kuo MYP, Chiang CP, Azuma M, Chen CW, Chia JS (2011). Increased prevalence of interleukin-17–producing CD4+ tumor infiltrating lymphocytes in human oral squamous cell carcinoma. Head and Neck-Journal for the Sciences and Specialties of the Head and Neck 33(9):1301-08. (SCI)
  8. Chia JS, Du JL, Hsu WB, Sun A, Chiang CP, Wang WB (2010). Inhibition of metastasis, angiogenesis, and tumor growth by Chinese herbal cocktail Tien-Hsien Liquid. Bmc Cancer 10:Article Number: 175. (SCI)
  9. Chen P. M., Chen Y. Y., Yu S. L., Sher S., Lai C. H., Chia J. S. 2010. Role of GlnR in acid-mediated repression of genes encoding proteins involved in glutamine and glutamate metabolism in Streptococcus mutans. Appl Environ Microbiol 76: 2478-2486. (NSC grant acknowledged, NSC 95-2320-B002-086-MY3 and NSC 96-3112-B002-031)
  10. Jung C. J., Zheng Q. H., Shieh Y. H., Lin C. S., and Chia J. S. 2009. Streptococcus mutans autolysin AtlA is a fibronectin-binding protein and contributes to bacterial survival in the bloodstream and virulence for infective endocarditis. Mol Microbiol. 74:888–902. (NSC grant acknowledged, NSC 95-2320-B002-086-MY3, and NSC 96-3112-B002-031)
  11. Shun C.T., Yeh C.Y., Chang C. J.,Wu S. H., Lien H. T., Chen J. Y.,Wang S. S, and Chia J.S. 2009. Activation of human valve interstitial cells by a viridans streptococci modulin induces chemotaxis of mononuclear cells. J. Infect. Dis. 199:1488-1496. (NSC grant acknowledged, NSC 95-2320-B002-086-MY3 and NSC 96-3112-B002-031)
  12. Sun A, Wang YP, Chia JS, Liu BY, Chiang CP (2009). Treatment with levamisole and colchicine can result in a significant reduction of IL-6, IL-8 or TNF-alpha level in patients with mucocutaneous type of Behcets disease. Journal of Oral Pathology & Medicine 38(5):401-05. (SCI)
  13. Chen PM, Chen HC, Ho CT, Jung CJ, Lien HT, Chen JY, Chia JS (2008). The two-component system ScnRK of Streptococcus mutans affects hydrogen peroxide resistance and murine macrophage killing. Microbes and Infection 10(3):293-301. (SCI)

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