What we do

We are interested in understanding bacterial pathogenesis, antibiotic resistance, bacterial community, and drug development.

The majority of our work has focused on H. pylori, an organism that infects 50% of people worldwide and is correlated with gastric cancer development. H. pylori adhesins and flagella-based motility play critical roles in the initiation of successful infection, and as such my studies have focused on regulation of these adhesin and flagella-related genes. Currently, our research focuses on identifying novel genes involved in bacterial metabolism and intracellular survival in Listeria monocytogenes. We have identified the regulon of a novel transcriptional regulator, Lmo1576, and implicated its regulation of metabolism in cytosolic survival of L. monocytogenes.

We have also collaborated with several other groups and clinical departments to survey the epidemiology of antimicrobial resistance in E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella spp., and Acinetobacter baumannii.

In addition, we have identified a number of small molecule inhibitors of bacterial PASTA kinases, a highly conserved family of proteins essential for virulence and antibiotic resistance in a variety of important pathogens including L. monocytogenes, Staphylococci, Enterococci, and Mycobacteria, through the collaboration with Dr. Sauer (UW-Madison). In addition to developing these small molecules as novel antibiotics, we are interested in understanding the signaling cascades downstream of the PASTA kinases that regulate antibiotic resistance and virulence, particularly in L. monocytogenes and methicillin-resistant Staphylococcus aureus.

Grants:

• 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  (4,680,000 NTD)

• 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- (1,100,000 NTD)

• 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- (1,490,000 NTD)

• 2024/06-2025/02. Principal investigator. Ministry of Education. Title: The New Southbound Policy: Overseas Internship Program. Grant number: 113005400N02 (278,605 NTD)

• 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- (13,500,000 NTD)

• 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. Grant number: NSTC 113-2321-B-A49-014- (4,100,000 NTD)

• 2024/01-2024/12. The Higher Education Sprout Project of the National Yang Ming Chiao Tung University and Ministry of Education (MOE), Taiwan. 113W020262 (450,180 NTD)

• 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 (700,000 NTD)

• 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 (299,000 NTD)

• 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: ??? (496,932 NTD)

• 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 (412,932 NTD)

• 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 (670,000 NTD)

• 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 (670,000 NTD)

• 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 (230,000 NTD)

• 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 (2,150,000 NTD)

• 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 (1,250,000 NTD)

• 2023/10-2025/12. The Higher Education Sprout Project of the National Yang Ming Chiao Tung University and Ministry of Education (MOE), Taiwan.  (400,000 NTD)

• 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-  (1,230,000 NTD)

• 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  (4,860,000 NTD)

• 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 (3,780,000 NTD)

• 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 (289,000 NTD)

• 2023/06-2023/09. Principal investigator. Ministry of Education. Title: The New Southbound Policy: Overseas Internship Program. Grant number: 111005400N01 (120,000 NTD)

• 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- (12,000,000 NTD)

• 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 (1,250,000 NTD)

• 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 (1,381,935 NTD)

• 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 (620,000 NTD)

• 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 (210,000 NTD)

• 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 (600,000 NTD)

• 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 (3,600,000 NTD)

• 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 (501,000 NTD)

• 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 (1,143,330 NTD)

• 2022/08. Principal investigator. Ministry of Science and Technology Research Promotion Center for Life Sciences. 2022 26th bacteriology conference. (250,000 NTD)

• 2022/06-2022/05. Principal investigator. BXB company industry-academia collaboration grant. Title: Isolation and characterization of probiotics with potential applications. Grant number:  (350,000 NTD)

• 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 (340,000 NTD)

• 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- (1,350,000 NTD)

• 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 (1,072,669 NTD)

• 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 (350,000 NTD)

• 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 (135,000 NTD)

• 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 (181,000 NTD)

• 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 (864,255 NTD)

• 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 (360,000 NTD)

• 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 (2020-2021-387,800 NTD; 2021-2022-419,700 NTD)

• 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 (4,500,000 NTD)

• 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 (154,000 NTD)

• 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 (2,600,000 NTD)