Research

Pneumococcal Infections

Background

• Streptococcus pneumoniae is a leading causative agent of community-acquired pneumonia and is one of the major pathogenic bacteria for which the rise of antimicrobial resistance is a serious concern.

Research Focus

• Comprehensive gene discovery by pan-GWAS: We use pan-genome-wide association studies (pan-GWAS) to systematically identify bacterial genes associated with pneumococcal disease phenotypes.
• Functional validation and causality: We perform molecular and cellular biology experiments to clarify the roles of candidate genes in disease development and to establish causal relationships.
• Age-dependent host immunity: Because pneumococcal infection substantially contributes to pneumonia-related mortality in older adults, we compare immune responses in young versus aged hosts using single-cell analysis and spatial gene expression profiling.
• Expected outcomes: By elucidating immune alterations specific to older adults, we aim to inform the development of next-generation vaccines and immunostimulatory therapies.

Streptococcus pyogenes Infections (Invasive Group A Streptococcal Disease)

Background

• Streptococcal toxic shock syndrome and necrotizing fasciitis are severe invasive infections with a mortality rate of approximately 30–40%. Many aspects of the disease mechanisms remain poorly understood.

Research Focus

• Genomic comparison and pan-GWAS: We compared whole-genome data from isolates derived from fulminant (severe) and non-fulminant cases and conducted pan-GWAS. Our analyses suggest that there is no single lineage unique to fulminant disease; instead, fulminant phenotypes may arise sporadically through the accumulation of mutations during infection.
• Beyond CovR/S: Multiple genetic variations, in addition to the CovR/S two-component regulatory system, appear to contribute to the transition toward fulminant disease. We are currently performing functional analyses of these variants and advancing the development of novel preventive and therapeutic strategies.
• Expected outcomes: We aim to identify biomarkers that predict progression to fulminant disease and to propose drug targets that suppress pathogenicity.

Microbiome Analysis

Background

• Diverse commensal microorganisms inhabit human skin, the oral cavity, and the gut. The balance of these microbial communities strongly influences health maintenance and disease onset or progression.

Research Focus

• High-resolution community and function profiling: Using metagenomics and bacterial single-cell approaches, we characterize the composition and functional potential of resident microbiomes, including microbes that are difficult to culture.
• Genetic resources and antimicrobial resistance: We investigate beneficial genetic resources as well as antimicrobial resistance genes, and analyze the extent to which genes are transmitted across species boundaries within microbial communities.
• Expected outcomes: By understanding the mechanisms driving the spread of resistance genes, we aim to contribute to new strategies for preventing the expansion of antimicrobial resistance and to support the development of next-generation probiotics.

Methods and Strengths

• Multi-omics integration: We integrate layered datasets—genomics, transcriptomics, proteomics, metabolomics, and more—to comprehensively understand pathogenicity and host responses.
• Single-cell technologies: We analyze gene expression and intercellular interactions at single-cell resolution.
• Computational science and machine learning: We leverage bioinformatics and machine learning to analyze large-scale genome and metagenome datasets.
• Clinical collaboration: In partnership with hospitals and public health organizations, we analyze clinical samples and work toward real-world implementation of preventive and translational solutions.