Research

Our research focuses on understanding how the gut microbiome influences host metabolism through the production of bioactive metabolites. We investigate the complex interplay between microbial communities and host physiology, with particular emphasis on bile acid metabolism, short-chain fatty acids, and amino acid derivatives.

Using advanced metabolomics platforms combined with metagenomics and mechanistic studies, we aim to identify key microbial metabolites that serve as signaling molecules affecting host metabolic health. This work has revealed novel pathways through which gut bacteria modulate energy homeostasis, lipid metabolism, and immune function.

Our findings have important implications for understanding metabolic diseases such as obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD), opening new avenues for microbiome-based therapeutic interventions.

Bile acids have emerged as critical signaling molecules that extend far beyond their classical role in lipid digestion. Our laboratory has pioneered research into how microbially-modified bile acids act through nuclear receptors (FXR) and membrane receptors (TGR5) to regulate glucose homeostasis, lipid metabolism, and energy expenditure.

We have identified specific bile acid species that are altered in metabolic diseases and cancer, providing potential biomarkers for disease diagnosis and prognosis. Our work has also uncovered novel therapeutic targets within the bile acid signaling network.

Recent work has shown that hyocholic acids shape neonatal immune tolerance, traced protection from chronic liver disease in females to a microbially produced bile acid, and used AI language models to expand the known human bile acid landscape by thousands of candidate species.

Current projects explore the gut-liver-brain axis mediated by bile acids and their potential as therapeutic agents for metabolic disorders and hepatocellular carcinoma.

Cancer cells exhibit profound metabolic reprogramming to support their rapid proliferation and survival. Our research applies comprehensive metabolomics approaches to identify metabolic vulnerabilities in gastrointestinal cancers, particularly hepatocellular carcinoma and colorectal cancer.

We integrate untargeted and targeted metabolomics with genomics data to discover novel biomarkers for early cancer detection and treatment response prediction. Our studies have revealed how the tumor microenvironment and gut microbiome contribute to cancer metabolism and progression.

This translational research program bridges basic discovery science with clinical applications, working closely with oncologists to develop metabolomics-based precision medicine strategies.

Traditional medicine systems, particularly Traditional Chinese Medicine (TCM), provide a rich source of therapeutic compounds. Our laboratory employs systems pharmacology approaches to understand the multi-target mechanisms of herbal medicines and to identify active compounds for modern drug development.

We integrate metabolomics, network pharmacology, and computational biology to map drug-target-disease networks. This systems-level understanding enables rational design of combination therapies and prediction of drug responses based on individual metabolic profiles.

Our research has successfully identified several promising compounds from medicinal herbs with demonstrated efficacy in preclinical models of metabolic diseases and cancer.