Introduction to Our Research
Our group focuses on understanding the fundamental mechanisms of protein oxidation and its implications for cellular function, ageing, and disease. Proteins, as the most abundant and functionally diverse macromolecules in living systems, are highly susceptible to damage by reactive oxygen species (ROS)—a natural by-product of cellular metabolism. Oxidative stress can lead to protein cleavage, amino acid side-chain modifications, or the attachment of oxidised carbohydrates and lipids, often rendering proteins dysfunctional. While some oxidative modifications, such as methionine and cysteine oxidations, are reversible, most forms of protein oxidation are irreversible, leading to an accumulation of damaged proteins, particularly with age or at sites of pathology, such as atherosclerotic plaques.
To further explore these mechanisms, we utilise liver organoids—three-dimensional models of liver tissue grown in the lab. These organoids enable us to study the effects of oxidative stress in a controlled, physiologically relevant environment, mimicking liver development, disease progression, and responses to therapies. By integrating quantitative proteomics with our liver organoid models, we investigate how ROS-driven protein oxidation impacts liver-specific functions, contributing to diseases such as fatty liver disease, fibrosis, and metabolic dysfunction. We aim to answer critical questions:
How and why do proteins become oxidised in the liver?
Do oxidised proteins lose function, or do they gain new, unexpected biological activities?
Is the accumulation of oxidised proteins a driving factor behind liver ageing and pathology, or is it merely a by-product?
By combining advanced organoid technologies with molecular and proteomic tools, our research bridges fundamental biology with translational applications, providing new insights into the molecular mechanisms of liver disease and potential therapeutic strategies to mitigate oxidative damage.