Wei Wei

Deorphanizing biochemical pathways that regulate nutrient metabolism in mammals

The human metabolome is remarkably complex, reflecting the intricate nature of metabolism itself—a dynamic network of thousands of biochemical reactions essential for sustaining life and adapting to environmental and physiological changes. Advanced analytical techniques such as mass spectrometry and NMR spectroscopy have revealed the presence of over 200,000 distinct endogenous metabolites in people. However, less than 30% of these metabolites have known or annotated biochemical pathways, leaving the majority as “orphan” metabolites with poorly understood origins, functions, and regulatory mechanisms. This significant knowledge gap limits our ability to fully understand how metabolism influences physiology and disease. Therefore, systematically deorphanizing these metabolites and mapping their biochemical contexts is critical for advancing our understanding of mammalian physiology and for uncovering new opportunities in therapeutic discovery.

Our lab is broadly interested in deorphanizing biochemical pathways that regulate nutrient metabolism, with the goal of uncovering new metabolic circuits that control physiology and contribute to disease. We focus on identifying previously uncharacterized metabolites, enzymes, and transporters, and determining their roles in nutrient sensing, energy balance, and metabolic signaling. Our current research centers on three major areas:

1. Taurine and its derived metabolites, where we aim to elucidate novel taurine-derived molecules and their physiological functions, particularly in appetite regulation and metabolic adaptation;
2. Glucose-derived metabolites, with an emphasis on uncovering overlooked branches of glucose metabolism that give rise to signaling molecules, reactive intermediates, or regulatory transporters involved in cellular communication and metabolic control;
3. Vitamins, especially those that serve as metabolic coenzymes or signaling modulators, where we investigate their unknown biochemical transformations and how these pathways intersect with cellular homeostasis.

By combining untargeted metabolomics, stable isotope tracing, enzymology, and mouse and human genetics, our goal is to illuminate hidden layers of mammalian metabolism and open new avenues for therapeutic intervention.