Our research primarily focuses on three major areas: fundamental studies on bacterial pathogenesis, mechanisms of antimicrobial resistance, and applied microbiology including the development of small-molecule therapeutics. The following is a summary of our research achievements in these areas over the past five years (2020-2025).
Basic Research: From 2020 to 2025, my research has focused on the physiology and pathogenesis of various human bacterial pathogens, particularly on gene regulation and metabolic pathways. In Helicobacter pylori, we demonstrated how CsrA coordinates flagellar assembly and host interactions. We further showed that Jhp0106, regulated by CsrA, may function as a glycosyltransferase involved in flagellar formation and bacterial colonization (Helicobacter. 2021 Apr;26(2):e12787). Through bioinformatic analyses, we also identified that Jhp0417 and Jhp0106 may both contribute to H. pylori flagellar biosynthesis. We then performed untargeted metabolomics and lipidomics using TRIzol, methanol, and MTBE extraction protocols to compare the jhp0417 mutant with wild-type H. pylori. The similar metabolomic profiles obtained suggest TRIzol can effectively isolate both metabolites and lipids from a single sample (Talanta. 2023 Jun 1;258:124416). We are currently expanding this work by applying multi-omics to investigate the CsrA regulatory network. Overall, these studies advance our understanding of bacterial pathogenic mechanisms and provide insights for future therapeutic strategies.
Antimicrobial Resistance: My AMR research integrates diagnostic assay development, antimicrobial gene surveillance, and mobile genetic element tracking. We validated the accuracy of mCIM and eCIM assays for carbapenemase detection and reported that co-carriage of multiple carbapenemases may affect assay performance (BMC Microbiol. 2020 Oct 17;20(1):315). For Staphylococcus lugdunensis, agar dilution proved to be a more reliable method for assessing oxacillin susceptibility (J Microbiol Immunol Infect. 2022 Apr;55(2):234-240). Genomic epidemiological studies revealed the widespread presence of carbapenemases, mcr, and qnr genes among multidrug-resistant strains of E. coli, K. pneumoniae, K. oxytoca, and A. baumannii (Front Microbiol. 2022 Mar 11;13:703113; J Glob Antimicrob Resist. 2022 Sep;30:241-248; Epidemiol Infect. 2023 Sep 7;151:e155; J Infect Public Health. 2024 Mar;17(3):457-463; J Microbiol Immunol Infect. 2024 Apr;57(2):288-299; Microbiol Spectr. 2024 Jun 4;12(6):e0038224; J Infect Public Health. 2024 Dec;17(12):102588; Int J Antimicrob Agents. 2025 Aug;66(2):107515). These resistance genes often reside on plasmids that enhance bacterial virulence, as demonstrated by increased pathogenicity in Galleria mellonella following plasmid transfer (BMC Microbiol. 2022 Jun 6;22(1):150; Infect Genet Evol. 2023 Jun;110:105420). We also found that E. coli strains isolated from elderly patients showed higher resistance levels compared to those from children or young adults (J Microbiol Immunol Infect. 2022 Apr;55(2):249-256), and that E. coli phylogroups differ in virulence, with group B2 strains being more pathogenic (Infect Genet Evol. 2023 Oct;114:105493). Importantly, nearly half of patients with recurrent UTIs were infected by the same clone, prompting our ongoing investigation into within-host evolution and shifts in virulence (BMC Microbiol. 2023 Mar 30;23(1):90; Gut Pathogens, In revision). In S. lugdunensis, we revealed associations between CRISPR-Cas types, antimicrobial resistance, sequence types, and lugdunin production, reflecting the complex dynamics between resistance and defense mechanisms (Microbiol Spectr. 2021 Dec 22;9(3):e0124721; J Microbiol Immunol Infect. 2023 Apr;56(2):292-298; Microbiol Spectr. 2023 Sep 21;11(5):e0129823; J Microbiol Immunol Infect. 2024 Apr;57(2):278-287). Most recently, we have focused on characterizing hypervirulent and extensively drug-resistant strains. Our findings show that ST2 A. baumannii strains exhibit elevated virulence and resistance (Int J Antimicrob Agents. 2024 Dec;64(6):107358), highlighting the emerging threat posed by these pathogens. We are now conducting detailed mechanistic studies across multiple species exhibiting similar high-risk profiles.
Applied Microbiology: My applied microbiology research seeks to translate basic science into therapeutic innovations, with a focus on probiotics, antimicrobial small molecules, and phage therapy. We characterized Lactiplantibacillus pentosus SLC13 and other local strains for their anti-pathogen activity and immunomodulatory properties (BMC Microbiol. 2022 Nov 21;22(1):277; BMC Microbiol. 2024 Mar 11;24(1):85), and are currently exploring their molecular mechanisms of inhibition. Against Gram-positive pathogens, we examined lugdunin-producing S. lugdunensis and found that its antimicrobial activity may be regulated by CRISPR-Cas systems. Ongoing work investigates the regulation of lugdunin biosynthesis (Microbiol Spectr. 2023 Sep 21;11(5):e0129823). In collaboration with the University of Malaya, we evaluated the indolenine derivative 4e and confirmed its anti-biofilm efficacy in both cell and animal models (Antimicrobial Agents and Chemotherapy, Accepted). Further studies are underway to investigate its derivatives and underlying mechanisms. Additionally, we demonstrated that low-energy shock wave therapy effectively treated UPEC-induced cystitis in a rat model (Int Urol Nephrol. 2025 Jan;57(1):49-61). Our phage therapy studies successfully isolated lytic phages targeting carbapenem-resistant Enterobacter cloacae, showing significant improvement in survival in infected larvae and murine models (Microbiology Spectrum, In revision). In the field of environmental microbiology, we reported that defect-engineered Bi₂Te₃ nanosheets exhibit enhanced haloperoxidase activity for marine antifouling applications (Small. 2024 Oct;20(43):e2401929). Most recently, we have initiated research on next-generation probiotics such as Akkermansia muciniphila and Bacteroides spp., exploring their potential in modulating the gut–liver axis for treating alcoholic liver disease and other metabolic conditions. These studies highlight our comprehensive development pipeline from strain isolation to translational application in microbiome-based therapeutics.
2025/08-2026/07. Co-Principal investigator. National Science and Technology Council. Title: Investigate the impact of the microbiota and metabolism on MASLDHCC and develop probiotics or post-biotics with the potential to improve and prevent MASLD-HCC. Grant number: NSTC 114-2314-B-A49-088-.
2025/08-2026/07. Co-Principal investigator. National Science and Technology Council. Title: Investigation into the evolution of carbapenem-resistant Escherichia coli within the host and its association with recurrent and multi-site infections. Grant number: NSTC 114-2635-B-385-001-.
2025/05-2026/04. Co-Principal investigator. National Science and Technology Council. Title: Establishment of research collaboration and technical service for national human microbiome core facilities. Grant number: NSTC 114-2740-B-A49-003-.
2025/05-2026/04. Co-Principal investigator. National Science and Technology Council. Title: The study of Akkermansia muciniphila and related metabolites as a biomarker or an adjuvant therapy for hepatocellular carcinoma (II). Grant number: NSTC 114-2321-B-A49-004-.
2025/01-2025/12. Principal investigator. KMU-NYCU joint grant. Exploring the metabolites of probiotics isolated from Taiwanese to evaluate their potential future. Grant number: NYCUKMU-114-I004.
2025/01-2025/12. Co-Principal investigator. Taipei City Hospital. Investigation of the role of gut microbiota in patients with primary premature ejaculation disorder and its effect on dapoxetine response. Grant number: TBD.
2025/01-2025/12. Principal investigator. Industry-academia collaboration grant. Title: Drug testing using an interstitial cystitis rat model. Grant number: 114A140063.
2025/01-2025/12. Principal investigator. CGMH-NYCU Joint Research Program. Title: Exploring the potential of low-energy shock waves and bacteriophages in the treatment of recurrent urinary tract infections (II): In vivo study. Grant number: 114W094004.
2025/01-2025/12. Co-Principal investigator. Taipei Tzu Chi Hospital research grant. Title: Study alternative mechanisms of Staphylococcus lugdunensis against lugdunin. Grant number: TBD.
2025/01-2025/12. Co-Principal investigator. Taipei Veterans General Hospital research grant. Title: Role of urinary microbiome in kidney calcium oxalate stone formation. Grant number: TBD.
2025/01-2025/12. Co-Principal investigator. Taipei Veterans General Hospital research grant. Title: Characterization of plasmids carrying carbapenemase genes in carbapenem-resistant Klebsiella pneumoniae and Escherichia coli isolated from urinary tract infection and bacteremia patients. Grant number: V114C-075.
2025/01-2025/12. Co-Principal investigator. Taoyuan General Hospital research grant (Ministry of Health and Welfare). Title: Investigation of the effects of carbapenemase-siderophore-carrying plasmids from Escherichia coli and Klebsiella pneumoniae on bacterial antimicrobial resistance and virulence. Grant number: PTH114126.
2025/01-2025/12. Co-Principal investigator. Taoyuan General Hospital research grant (Ministry of Health and Welfare). Title: Investigation of the antibiotic resistance, virulence-associated genes, and phenotypes among different species within the Klebsiella pneumoniae species complex. Grant number: PTH-114012.
2025/01-2025/12. Co-Principal investigator. National Taiwan University Hospital research grant (Hsin-Chu branch). Title: Exploring the characteristics of hypervirulent and carbapenem-resistant Pseudomonas aeruginosa (I): phenotypic and genotypic analysis. Grant number: 114-HCH064.
2024/12. Principal investigator. Ministry of Science and Technology Research Promotion Center for Life Sciences. 2024 Taiwan Society for Microbiology Annual conference.
2024/08-2028/07. Principal investigator. Industry-academia collaboration grant (Biomedical Industry Ph.D. Program, NYCU). Title: Development of next-generation probiotic products with enhanced metabolic disease improvement efficiency. Grant number: 113A140106.
2024/08-2025/07. Co-Principal investigator. En Chu Kong Hospital research grant. Title: Investigation of the evolution of carbapenem-resistant Escherichia coli in the host and its association with recurrent infections (second year). Grant number: ECKH_W11303.
2024/08-2027/07. Principal investigator. National Science and Technology Council (Excellent Young Scholars Fund). Title: Development of novel indolenine-substituted pyrazole small molecules to combat multidrug-resistant staphylococcal infections and investigation of their antibacterial and anti-biofilm mechanisms. Grant number: 113-2628-B-A49-011-MY3.
2024/08-2025/07. Co-Principal investigator. National Science and Technology Council. Title: Combating Carbapenem Resistance in Klebsiella pneumoniae Complex and Enterobacteriaceae Complex: Taiwan's Diverse Strategies. Grant number: 113-2314-B-002-129-.
2024/08-2025/07. Co-Principal investigator. National Science and Technology Council. Title: Investigation of the anti-lugunin mechanism of Staphylococcus lugdununsis. Grant number: 113-2320-B-182A-014-.
2024/06-2025/02. Principal investigator. Ministry of Education. Title: The New Southbound Policy: Overseas Internship Program. Grant number: 113005400N02.
2024/05-2025/04. Co-Principal investigator. National Science and Technology Council. Title: Establishment of research collaboration and technical service for national human microbiome core facilities. Grant number: NSTC 113-2740-B-A49-003-.
2024/05-2025/04. Co-Principal investigator. National Science and Technology Council. Title: The study of Akkermansia muciniphila and related metabolites as a biomarker or an adjuvant therapy for hepatocellular carcinoma (I). Grant number: NSTC 113-2321-B-A49-014-.
2024/01-2024/12. The Higher Education Sprout Project of the National Yang Ming Chiao Tung University and Ministry of Education (MOE), Taiwan. 113W020262.
2024/01-2024/12. Principal investigator. CGMH-NYCU Joint Research Program. Title: Exploring the potential of low energy shock waves and bacteriophages in the treatment of recurrent urinary tract infections (I): In vitro study. Grant number: CGMH-NYCU-113-CORPG8P0211.
2024/01-2024/12. Co-Principal investigator. National Taiwan University Hospital research grant (Hsin-Chu branch). Title: Isolation and characterization of lytic bacteriophages targeting carbapenem-resistant Enterobacter species. Grant number: 113-HCH057.
2024/01-2024/12. Co-Principal investigator. Research Project of Shin Kong Wu Ho-Su Memorial Hospital. Title: Screening and investigation of antibacterial and antivirulence botanical compounds. Grant number: 2024SKHAND011.
2024/01-2024/12. Co-Principal investigator. Research Project of Shin Kong Wu Ho-Su Memorial Hospital. Title: Investigation of the in vitro evolution of Acinetobacter baumannii under carbapenem-selected stress. Grant number: 2024SKHAND009.
2024/01-2024/12. Co-Principal investigator. Taipei Veterans General Hospital research grant. Title: To investigate the evolution of pathogen within host and its pathogenesis of recurrent urinary tract infection (II). Grant number: V113C-200.
2024/01-2024/12. Co-Principal investigator. Taipei Veterans General Hospital research grant. Title: The change of saliva microbiota after interventional sialendoscopy in sialolithiasis patients. Grant number: V113C-192.
2024/01-2024/12. Principal investigator. Yen Tjing Ling Medical Foundation, Taiwan. Title: Characterization of colistin resistance mechanisms in colistin-nonsusceptible K. pneumoniae and the role(s) of mcr-carrying plasmids in its pathogenesis. Grant number: CI-113-29.
2023/12-2024/11. Principal investigator. Company industry-academia collaboration grant. Title: Isolation, characterization, and product development of probiotics with potential applications (I). Grant number: 112A40114Y.
2023/10-2024/09. Principal investigator. Company industry-academia collaboration grant. Title: Isolation and characteristics of probiotics with potential applications for improving the gastrointestinal health of animals (I). Grant number: 112A40105Y.
2023/10-2025/12. The Higher Education Sprout Project of the National Yang Ming Chiao Tung University and Ministry of Education (MOE), Taiwan.
2023/08-2024/07. Co-Principal investigator. National Science and Technology Council. Title: Multi-faceted analysis of the evolution and drug resistance of endemic uropathogens: a 24-year longitudinal research from a Southern Taiwan Medical Center. Grant number: 112-2314-B-006-060-.
2023/08-2026/07. Principal investigator. National Science and Technology Council. Title: Multi-faceted analysis of the evolution of Escherichia coli within-host and its interaction with microbiota to explore the mechanisms of recurrent urinary tract infections. Grant number: 112-2320-B-A49-045-MY3.
2023/08-2026/07. Co-Principal investigator. National Science and Technology Council. Title: Effects of Low Energy Shock Waves on urinary tract bacteria- in vitro and in experimental cystitis model in rats. Grant number: NSTC 112-2314-B-182A-135-MY3.
2023/08-2024/07. Co-Principal investigator. En Chu Kong Hospital research grant. Title: Investigation of the evolution of carbapenem-resistant Escherichia coli in the host and its association with recurrent infections. Grant number: ECKH_W11201.
2023/06-2023/09. Principal investigator. Ministry of Education. Title: The New Southbound Policy: Overseas Internship Program. Grant number: 111005400N01.
2023/05-2024/04. Co-Principal investigator. National Science and Technology Council. Title: Establishment of research collaboration and technical service for national human microbiome core facilities. Grant number: NSTC 112-2740-B-A49-002-.
2023/03-2024/02. Principal investigator. Company industry-academia collaboration grant. Title: Isolation and characterization of probiotics with potential applications for the prevention of vaginal infections (I). Grant number: 112A40071Y.
2023/03-2024/02. Co-Principal investigator. Chang Gung Medical Foundation CMRP grant. Title: Characterization of lugdunin activity produced by Staphylococcus lugdunensis isolates from 2003-2020 in Chang Gung Memorial Hospital: epidemiology, antibacterial activity, association with different genotypes, and gene regulation. Grant number: CMRPG3N0091.
2023/01-2023/12. Co-Principal investigator. Taipei Veterans General Hospital research grant. Title: Investigation of within-host bacterial evolution and pathogenesis in polymicrobial urinary tract infections. Grant number: V112C-203.
2023/01-2023/12. Principal investigator. Yen Tjing Ling Medical Foundation, Taiwan. Title: Characterization of uropathogenic Escherichia coli in different phylogenetic groups. Grant number: CI-112-19.
2023/01-2023/12. Co-Principal investigator. Taipei Veterans General Hospital research grant. Title: To investigate the evolution of pathogen within host and its pathogenesis of recurrent urinary tract infection. Grant number: V112C-208.
2022/08-2025/07. Co-Principal investigator. National Science and Technology Council. Title: The effects of testicular microenvironment on spermatogenesis in men with non-obstructive azoospermia - Analysis of testicular steroidogenesis patterns and metaproteomics of testicular bacteria microbiome. Grant number: MOST 111-2314-B-075-044-MY3.
2022/08-2023/07. Co-Principal investigator. En Chu Kong Hospital research grant. Title: Investigation of the phenotypic and genomic evolution of carbapenem-resistant Escherichia coli in the host. Grant number: ECKH_W11105.
2022/08-2023/07. Co-Principal investigator. Chang Gung Medical Foundation CMRP grant. Title: Characterization of an endemic Staphylococcus lugdunensis type 6 in a medical center. Grant number: CMRPG3M1041.
2022/08. Principal investigator. Ministry of Science and Technology Research Promotion Center for Life Sciences. 2022 26th bacteriology conference.
2022/06-2022/05. Principal investigator. BXB company industry-academia collaboration grant. Title: Isolation and characterization of probiotics with potential applications. Grant number: TBC
2021/10-2022/09. Principal investigator. BENED Biomedical company industry-academia collaboration grant. Title: The role(s) of probiotics on anti-Helicobacter pylori activity and its mechanisms (II). Grant number: YM110J063.
2021/08-2022/07. Principal investigator. Ministry of Science and Technology, Republic of China, Taiwan. Title: Investigate the evolution of Escherichia coli within host and its pathogenesis of recurrent urinary tract infection. Grant number: 110-2320-B-A49A-524-.
2021/08-2022/07. Co-Principal investigator. Chang Gung Medical Foundation CMRP grant. Title: Determination of the association of CRISPR-Cas system with oxacillin susceptibility, MLST sequence types, and virulence in Staphylococcus lugdunensis. Grant number: CMRPG3L0631.
2021/01-2021/12. Principal investigator. National Yang-Ming University-Far Eastern Memorial Hospital Joint Research Program, Taiwan. Title: Characterization of carbapenem-non-susceptible Acinetobacter isolated from patients with bloodstream infection. Grant number: 110DN14.
2021/01-2021/12. Principal investigator. Yen Tjing Ling Medical Foundation, Taiwan. Title: Characterization of E. coli isolated from patients with recurrent urinary tract infections. Grant number: CI-110-13.
2020/10-2021/10. Principal investigator. Ministry of Science and Technology, Republic of China, Taiwan. Title: Increasing the international visibility of Taiwan society of microbiology. Grant number: 109-2926-I-010-505.
2020/10-2021/09. Co-Principal investigator. Chang Gung Medical Foundation CMRP grant. Title: Determination of oxacillin susceptibility and SCCmec structure of predominant sequence type 3, 6, and 27 Staphylococcus lugdunensis in Taiwan. Grant number: CMRPG3K1421.
2020/08-2021/07. Principal investigator. BENED Biomedical company industry-academia collaboration grant. Title: The role(s) of probiotics on anti-Helicobacter pylori activity and its mechanisms. Grant number: YM109C036.
2020/08-2022/07. Co-Principal investigator. En Chu Kong Hospital research grant. Title: Molecular characterization of carbapenem-resistant Enterobacteriaceae in a regional teaching hospital in Taiwan, 2011-2019. Grant number: ECKH_W10901 & ECKH_W11001.
2020/08-2023/07. Principal investigator. Ministry of Science and Technology, Taiwan. Title: Characterization of the role(s) of PASTA kinase-mediated signaling pathways in resistance of Staphylococcus aureus to β-lactam antibiotics. Grant number: 109-2320-B-010 -036 -MY3.
2019/10-2020/10. Principal investigator. Ministry of Science and Technology, Taiwan. Title: Connect American and Taiwan societies for microbiology to promote the international visibility of microbiology research in Taiwan . Grant number:108-2911-I-010-508.
2017/10-2019/10. Principal investigator. Postdoctoral Research Abroad Program, Ministry of Science and Technology, Taiwan. Title: Characterization of Listeria monocytogenes CFPTS gene cluster in central nervous systemic infection. Grant number: 106-2917-I-564-070.