Bacteria, similar to higher animals, exhibit remarkable versatility by altering their behaviors in different environments. While microbiologists typically study bacteria under simple lab conditions, our knowledge of bacterial physiology in their natural habitats (e.g. humans, soils) is limited. Our lab is dedicated to using various state-of-the-art approaches to unravel how bacterial pathogens behave in the human body. By characterizing the in-situ physiology of opportunistic pathogens (such as Pseudomonas aeruginosa), we aim to provide molecular insights into developing new therapeutics (such as antisense therapy) to combat challenging bacterial infections.

By directly examining bacterial gene expression in clinical samples, we have begun to understand P. aeruginosa physiology in humans. We discovered a key small regulatory RNA called SicX, which plays a critical role in orchestrating the transition between bacterial chronic persistence and acute exacerbation. Leveraging information of bacterial gene expression within human hosts, we can better understand how P. aeruginosa responds to host environmental cues and changes lifestyles accordingly. Building upon this discovery, our lab focuses on addressing several major questions:

• How does SicX sRNA govern bacterial chronic or acute infection? We've established the roles of SicX in vitro in response to oxygen deprivation, but how it governs bacterial lifestyle choice during infection requires further study. Filling this gap is critical for designing new therapies against this important pathogenic trait.

• What are the roles of other sRNAs in human infections? Our discovery of SicX is just the tip of the iceberg. Despite considerable efforts to identify bacterial sRNAs, our knowledge of their identities and functions remains limited to a few well-studied examples. Our goal is to uncover and study diverse sRNAs related to infections.

• How does inter and intra-species communication impact the progression and outcomes of bacterial infections? Bacterial populations within the host often exhibit physiological heterogeneity and genetic diversity. Moreover, various microbial species often coexist and show intricate interactions with host cells. We aim to explore how novel mechanisms of cell-cell communication can shape the dynamics of bacterial infections.

While our primary focus is on bacterial infectious diseases, we also have a keen interest in studying the behaviors of non-pathogenic bacteria in natural environments, such as soil. Overall, our lab is dedicated to unraveling the multifaceted nature of diverse bacterial behaviors and their broader implications.