臺北醫學大學 醫學科學研究所

Host factors play a critical role in regulating bacterial virulence and the progression of systemic lethal diseases. Consequently, targeting the interactions between bacteria and the host represents a promising strategy for developing effective therapies against these infections. The long-term goal of my research is to investigate host-pathogen interactions to uncover novel approaches for managing infectious diseases. In particular, We focus on the roles of neutrophil extracellular traps (NETs), bacterial extracellular DNA, and bacterial membrane vesicles. Ongoing research projects include:

Infective endocarditis (IE) is a prototypical biofilm-associated infectious disease of the cardiovascular system, characterized by a high mortality rate (Fig. 1). Clinical management of IE still relies on prolonged administration of high-dose antibiotics and is often complicated by frequent recurrence. My research has demonstrated that host factors significantly enhance the virulence of IE pathogens. For instance, platelets contribute to biofilm formation and antibiotic resistance in IE pathogens (Fig. 2). Furthermore, aggregates formed between bacteria and platelets stimulate infiltrating neutrophils to release neutrophil extracellular traps (NETs), which in turn activate additional platelets and promote thrombus formation. This cascade contributes to the expansion and maturation of IE vegetations (Fig. 3).

We further demonstrated the critical roles of autolysin (AtlA)-mediated extracellular DNA (eDNA) release and membrane vesicle production in biofilm formation in IE (Fig. 4). In addition, we identified key bacterial virulence factors, including LiaR, PCP, and PrsA, that contribute to eDNA release and membrane vesicle production, both of which promote bacterial biofilm formation in vivo. The underlying molecular mechanisms by which these factors regulate biofilm development will be further investigated (Fig. 5).

Infections are known risk factors for the development of autoimmune diseases. Anti-DNA antibodies, for example, are a key diagnostic marker for systemic lupus erythematosus (SLE) and are thought to contribute to disease pathology. Neutrophil extracellular traps (NETs) are considered a primary source of extracellular DNA and other autoantigens that may trigger autoimmune responses. Our preliminary data show that intravenous infection with oral streptococci or glucosyltransferase (Gtf) leads to the production of anti-DNA antibodies. We hypothesize that oral streptococci within dental biofilms release Gtf, which either binds to extracellular DNA or induces NET formation, thereby promoting anti-dsDNA antibody production and contributing to autoimmune pathogenesis. The underlying mechanisms will be further investigated.

We also investigate the role of neutrophil extracellular traps (NETs) in other infectious diseases in collaboration with clinical physicians.

(In collaboration with Dr. Chen, National Taiwan University Hospital)

We collect clinical fibrin samples to investigate the role of bacteria-induced NETs in the development of catheter-related central venous stenosis and associated thrombosis.

(In collaboration with Dr. Kuo, National Taiwan University Hospital)

We collect clinical samples to investigate the involvement of NETs in the pathogenesis of vaccine-induced adverse events.