Dysregulation of lipid metabolism is a key contributing factor to multiple metabolic diseases, including cardiovascular diseases that account for over 40% of deaths globally, as well as diabetes, hypertension, fatty liver disease, and neurodegenerative disorders. The fundamental approach to preventing and treating metabolic diseases lies in elucidating their pathogenic mechanisms, identifying therapeutic targets, and developing treatment strategies. Genetic factors have a significant impact on human lipid metabolism. History has witnessed multiple successful examples of translating human genetic research into clinically used drugs. One example is the development of PCSK9 inhibitors as lipid-lowering drugs, which is attributable to human genetic studies that identified PCSK9 mutations in individuals with dyslipidemia. Although significant progress has been made in understanding the molecular mechanisms of lipid metabolism, what we know about the genes and SNPs underlying metabolic diseases is very limited.
This project focuses on cholesterol metabolism, investigating its synthesis, absorption, as well as the transport and transformation of related metabolites. We aim to elucidate the core regulatory mechanisms and critical steps in cholesterol metabolism.
Our team has long been at the forefront of cholesterol metabolism studies, achieving a series of highly influential breakthroughs published in top-tier journals such as Nature, Science, and Cell.