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PGN Impact on Host Innate Immunity
We explore how circulating peptidoglycan fragments (PGNs) interact with host pattern-recognition receptors, including NOD1, NOD2 and PGRPs to modulate immune signaling.
Our bodies must delicately balance tolerating commensal PGN signals from our gut microbiota while mounting appropriate inflammatory responses to pathogens. We seek to elucidate specific mechanistic details of these bacterial molecules use to trigger, suppress, or train host innate immunity in both healthy states and inflammatory diseases.
Key Publications:
Antibody neutralization of microbiota-derived circulating peptidoglycan dampens inflammation and ameliorates autoimmunity (Nature Microbiology, 2019)
Gut microbiota-derived GlcNAc-MurNAc is a TLR4 agonist that protects the host gut (Nature Communications, 2025)
Intracellular structural modifications of natural PGN fragments preceding NOD2 signaling (PNAS, 2026)
Inter-kingdom Crosstalk
Beyond the host immune system, we investigate how gut microbiota-derived PGNs act as potent signaling keys that regulate fungal growth, virulence, and morphological transitions.
Our primary focus is on the opportunistic human pathogen Candida albicans, where bacterial PGNs are known to trigger the critical transition from yeast to highly invasive hyphal forms.
We seek to identify the specific fungal transporters and sensors, such as Opt4 and Ssy1, responsible for uptake and detecting bacterial PGNs. Understanding this inter-kingdom communication will pave the way for novel anti-virulence therapies to combat systemic fungal infections.
Key Publications:
A peptidoglycan storm caused by β-lactam antibiotic's action on host microbiota drives Candida albicans infection (Nature Communications, 2021)
Molecular docking reveals critical residues in Candida albicans Cyr1 for peptidoglycan recognition and hyphal growth (ACS Infectious Diseases, 2023)
Candida albicans Ssy1 is the extracellular sensor of gut microbiota-derived peptidoglycan fragments mediating invasive hyphal growth in the host (Nature Communications, 2025)
Chemical and Analytical Toolkits
To decode the intricate molecular conversations of the microbiota, we develop and design innovative chemical biology tools. Our work involves synthesizing natural PGNs of varying structures, robust chemoselective chemical probes, creating novel strategies to derivatize and functionalize natural unprotected PGNs, and building advanced mass spectrometry platforms.
This includes our PGN_MS2 database, an automated in silico MS/MS spectral prediction library built for high-throughput peptidoglycan profiling. This open-access toolkit enables researchers to rapidly deconvolve complex LC-MS/MS data and uncover previously unknown bioactive bacterial PGNs in the gut.
Key Publications:
In silico MS/MS prediction for peptidoglycan profiling uncovers novel anti-inflammatory peptidoglycan fragments of the gut microbiota (Chemical Sciences, 2024)
Discovery of bioactive peptidoglycan fragments from Lactobacillaceae that confer intestinal protection in hosts (Cell Chemical Biology, 2026)
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