以下所列是本研究室近年之研究主題與代表性成果，包括學生參與之研究計畫、跨領域合作，以及微生物基因體學與長讀長定序技術於臨床與生物學問題上的應用。The themes summarized below reflect the evolving research directions of the laboratory in recent years, including representative projects, collaborative studies, and student-involved publications. These research activities involve graduate students, interdisciplinary collaborations, and the application of comparative genomics and long-read sequencing technologies to clinically and biologically important microbial systems.

Antimicrobial Resistance & Mobile Genetic Elements

Research in this area has focused on the role of mobile genetic elements — including plasmids, integrative and conjugative elements, resistance islands, and transposons — in the emergence, dissemination, and evolution of antimicrobial resistance among clinically important bacteria.

Studies from the laboratory have included comparative genomics of multidrug-resistant pathogens, characterization of resistance-associated mobile elements, and investigation of regulatory mechanisms linking antimicrobial resistance with bacterial adaptation and virulence.

Plasmid-mediated regulation of antimicrobial resistance and virulence

One major research direction in the laboratory has focused on the role of plasmid-associated regulatory elements in antimicrobial resistance and bacterial adaptation.
An early study identified RamAp, an IncHI2 plasmid-borne efflux pump regulator in Salmonella enterica, demonstrating how horizontally acquired regulatory genes may contribute to antimicrobial resistance and bacterial physiology.
This project was initially conducted by Hong YP, an in-service doctoral trainee from the Taiwan Centers for Disease Control (CDC), and was later expanded through functional and regulatory studies involving graduate students from the laboratory, including Yeh WS, Wan MS, Wu YC, and laboratory alumnus Hong YM.
Subsequent work further investigated downstream gene regulation and the functional roles of RamAp in bacterial physiology, oxidative stress response, motility, and virulence, extending the project from plasmid-associated antimicrobial resistance toward broader questions of bacterial adaptation and pathogenicity.

Related publications

• Hong YP, Wang YW, Chen BH, Song HY, Chiou CS, Chen YT*. RamAp, an efflux pump regulator carried by an IncHI2 plasmid. Antimicrob Agents Chemother. 2022. 66(1):e01152-21.
• Plasmid-borne transcriptional regulator RamAp modulates Salmonella genes for environmental and host adaptation. Front Microbial. 2026. [Accepted]

Outbreak Genomics & Emerging Pathogens

Research in this area focuses on the genomic epidemiology of clinically important bacterial pathogens using comparative genomics and whole-genome sequencing approaches.

Studies from the laboratory have investigated hospital-associated outbreaks, dissemination of high-risk bacterial lineages, and the genomic characteristics of emerging pathogens, including Elizabethkingia anophelis, methicillin-resistant Staphylococcus aureus (MRSA), and Mycoplasma pneumoniae.

The laboratory works in close collaboration with clinician-scientists and in-service doctoral trainees from affiliated hospitals, integrating clinical microbiology, infectious disease practice, and comparative genomics approaches for the investigation of hospital-associated pathogens and emerging bacterial lineages.

Genomic epidemiology of Elizabethkingia anophelis

One major research direction in this area has focused on the genomic epidemiology and hospital-associated transmission of Elizabethkingia anophelis, an emerging opportunistic pathogen associated with healthcare settings.

This project originated through collaboration with clinician-scientists and medical laboratory professionals from Changhua Christian Hospital, particularly Lee YL (infectious disease physician and in-service doctoral trainee) and Chang HL (medical technologist and graduate student). Subsequent studies involved graduate students from the laboratory, including Liu KM, Liao YC, Huang JC, Yao YC, Li RY, Hsu MH, and Lin YZ.

Research from this project identified a prolonged hospital-associated outbreak linked to contaminated water systems and further characterized the genomic evolution and lineage diversification of Elizabethkingia anophelis strains in Taiwan. Additional studies explored genomic islands and efflux pump-associated tolerance to disinfectants in outbreak-associated strains.

The project also led to the characterization of the unusual Elizabethkingia genomospecies 2-6 lineage and multiple conference presentations at the Molecular Biology Society of Japan (MBSJ), including poster and oral presentations by graduate students from the laboratory.

For more: 有些細菌不是突然出現，而是我們現在才看得懂

Related publications

• Liu KM, Chang HL, Hsu MH, Lin YZ, Lee YL, Chen YT*. Complete Genome Sequencing of Elizabethkingia sp. Strain 2-6. Microbiol Resour Announc. 2019.
• Lee YL, Liu KM, Chang HL, Lin JS, Kung FY, Ho CM, Lin KS, Chen YT*. A dominant strain of Elizabethkingia anophelis emerged from hospital water system to cause a three-year outbreak in a respiratory care center. J Hosp Infect. 2021.
• Lee YL, Liu KM, Chang HL, Liao YC, Lin JS, Kung FY, Ho CM, Lin KH, Chen YT*. The evolutionary trend and genomic features of an emerging lineage of Elizabethkingia anophelis strains in Taiwan. Microbiol Spectr. 2022.

Comparative genomics of human-adapted MRSA CC398 lineages

Another major research direction has focused on the comparative genomics and evolution of methicillin-resistant Staphylococcus aureus (MRSA), particularly human-adapted CC398 and ST1232 lineages circulating in Taiwan.

This project was primarily led by Wu TH, a pediatrician from Show Chwan Memorial Hospital and in-service doctoral trainee in the laboratory, together with graduate student Wu YC. Additional contributions were made by laboratory members including Li RY, Wan MS, and Yeh WS.

Studies from this project investigated the genomic characteristics, phylogenetic relationships, and mobile genetic elements associated with emerging MRSA lineages, with particular emphasis on SCCmec structures, prophage-associated virulence factors, and the adaptation of livestock-associated MRSA lineages to human hosts.

In addition to peer-reviewed publications, this research direction has also been presented at the Molecular Biology Society of Japan (MBSJ) through poster and oral presentations by both doctoral and graduate students from the laboratory.

For more: 基因體告訴我們的事：關於人類適應型 MRSA CC398

Related publications

• Wu TH, Wu YC, Yeh WS, Wan MS, Li RY, Lee CY, Fang YP, Yang YY, Chang YF, Chen YT.* Genomic and phylogenetic characterization of human-adapted methicillin-resistant Staphylococcus aureus clonal complex 398 lineages in Taiwan. Microbiol Spectr. 2025. 0:e02090-25.
• Additional studies on MRSA ST1232 comparative genomics are currently under peer review.

Long-read Sequencing & Microbial Genomics

Research in this area focuses on the development and application of long-read sequencing approaches for microbial genomics, particularly for challenging host-associated or low-abundance microbial systems.

Studies from the laboratory have explored nanopore adaptive sampling strategies and bioinformatics workflows for genome reconstruction from complex samples with overwhelming host DNA background and substantial reference divergence. Current work has primarily focused on Wolbachia associated with mosquitoes and other insects.

These projects integrate long-read sequencing, comparative genomics, and computational analysis to facilitate the recovery and characterization of difficult-to-sequence microbial genomes.

Nanopore adaptive sampling for host-associated microbial genomics

One major research direction in this area has focused on the development of nanopore adaptive sampling strategies for genome reconstruction from challenging host-associated microbial systems.

This project primarily investigates Wolbachia, an intracellular bacterial symbiont associated with mosquitoes and other insects, where genome recovery is often complicated by overwhelming host DNA background and substantial reference divergence. Research from the laboratory has explored long-read sequencing workflows and bioinformatics approaches for the recovery and characterization of difficult-to-sequence microbial genomes directly from complex biological samples.

Early development of this project involved graduate students Yeh WS and Wan MS, followed by experimental work conducted primarily by Wu YC and Yang CH. Bioinformatics analysis and workflow optimization were subsequently led by Huang WK, who continues to refine computational approaches for adaptive sampling-based microbial genomics.

Recent work has further expanded through collaboration with entomology researchers, extending these approaches to additional insect-associated microbial systems. Current projects involving incoming graduate students Chung H and Lee YC continue to build upon this sequencing and bioinformatics framework for host-associated microbial genomics.

Fore more: 從「讀取」到「選擇」：Adaptive Sampling 如何改變基因體定序的可能性

Related publications

• Huang WK, Yang CH, Lee YC, Wu YC, Chen YT, Wan MS, Yeh WS, Hong YP, Wu TH, Li JC, Liu WL, Chen CH, Chen YT*. Adaptive sampling-based enrichment enables genome reconstruction of intracellular symbionts despite host background and reference divergence. bioRxiv. 2026.03.25.714109.
• Yu HY, Chen BY, Chen YT, Huang WK, Yang CH, Wu YC, Wan MS, Yeh WS, Got FG, You H, Too PK, Ng SH, Cai Y, Li JC, Chen CH, Liu WL*. Establishment and characterization of a Wolbachia (wAlbB)-infected Aedes aegypti line (Tw-Kao) for dengue control. PLOS Neglected Tropical Diseases. 2026. 20(5):e0014222.

Collaborative & Interdisciplinary Research

The laboratory also participates in collaborative and interdisciplinary studies involving microbial genomics, host-associated microbes, animal health, and translational biomedical research.

One collaborative research direction involved genomic characterization of psychobiotic and probiotic-associated microbial systems in partnership with biotechnology researchers and industry collaborators. This work included sequencing and analysis of probiotic strains such as Lactobacillus fermentum PS150, with major contributions from graduate student Chien SP.

Additional interdisciplinary collaborations were conducted with biomedical researchers at the National Health Research Institutes (NHRI), where the laboratory contributed sequencing and genomic analysis for experimental mouse-derived cell line systems related to lipid metabolism and cancer biology. These studies involved graduate students Huang JC, Yao YC, and Liao YC.

Other collaborative projects have included antimicrobial resistance studies in bovine mastitis pathogens, genomic epidemiology of carbapenem-resistant Enterobacterales, and spectroscopy-assisted antimicrobial susceptibility studies.

Through these interdisciplinary collaborations, the laboratory contributes comparative genomics, long-read sequencing, and bioinformatics approaches to biologically and clinically important research questions across multiple fields.

Related publications

• Huang CL, Chu HF, Wu CC, Deng FS, Wen PJ, Chien SP, Chao CH, Chen YT, Lu MK, Tsai TC*. Exopolysaccharide is the Potential Effector of Lactobacillus fermentum PS150, a Hypnotic Psychobiotic Strain. Front Microbiol. 2023. 14:1209067.
• Cheng YH, Ko YC, Ku HJ, Huang CC, Yao YC, Liao YT, Chen YT, Huang SF, Huang LR*. Novel paired cell lines for the study of lipid metabolism and cancer stemness of hepatocellular carcinoma. Front Cell Dev Biol. 2022. 10:821224.