SUMMARY
Jun Liu, M.D., Ph.D., leads a discovery-driven research program focused on defining the cellular mechanisms that regulate lipid metabolism and how their dysregulation leads to disease.
Dr. Liu and his team combine hypothesis-driven experimentation with unbiased discovery platforms. These platforms include:
- Biochemistry.
- Cell biology.
- Genetics.
- Lipidomics and proteomics.
- Stable-isotope tracing.
- Advanced imaging.
- Engineered animal and human-relevant models.
Using this integrated approach, the team identifies new enzyme regulators, defines causal mechanisms, and establishes general principles governing how lipid synthesis, turnover and utilization are coordinated across cells, organs and tissues. Dr. Liu's laboratory also investigates how these regulatory systems adapt to nutritional conditions and metabolic stress, and how their disruptions predispose patients to obesity, insulin-resistant diabetes, dyslipidemia, steatotic liver disease — also known as fatty liver disease — and cancer.
The long-term goal of Dr. Liu's research is to generate mechanistic insight that provides a conceptual framework for understanding how lipid biochemistry and cell biology are integrated with systemic physiology.
Focus areas
-
Mechanistic dissection of intracellular lipolysis. Dr. Liu's laboratory studies how cells regulate the breakdown of stored triglycerides to meet their energy and metabolic needs. A major focus is adipose triglyceride lipase (ATGL), the enzyme that releases fatty acids from intracellular triglycerides. Dr. Liu and his team discovered that two small proteins — G0/G1 switch gene 2 (G0S2) and hypoxia-inducible lipid droplet-associated protein (HILPDA), also known as hypoxia-inducible gene 2 (HIG2) — act as molecular brakes on ATGL.
In response to nutrient availability, G0S2 enables adipocytes and hepatocytes to adjust fatty acid mobilization as metabolic demands change. Under low-oxygen conditions, cancer cells in solid tumors produce HILPDA, which suppresses fatty acid release and enhances cell survival by limiting oxidative stress.
Together, these studies show how cells fine-tune lipolysis in response to nutrient and oxygen cues. They also demonstrate how disruption of these regulatory mechanisms contributes to the development of metabolic disease and cancer.
-
Functional determination of genetic variants in lipid enzymes. Dr. Liu's laboratory investigates how missense mutations in lipid-metabolizing enzymes disrupt metabolic homeostasis. A major focus of his research is patatinlike phospholipase domain-containing protein 3 (PNPLA3), which harbors a common variant strongly associated with steatotic liver disease. Dr. Liu and his team identified PNPLA3 as a lipase that selectively hydrolyzes polyunsaturated triglycerides, an activity important for intracellular membrane remodeling and packaging triglycerides into lipoproteins for secretion. Their findings suggest that loss of this function in the PNPLA3 variant is a key driver of disease.
Dr. Liu's laboratory also studies how defects in fatty acid oxidation, or its regulation, reprogram hepatic and adipose metabolism, leading to oxidative stress, inflammation and systemic metabolic dysfunction.
Collectively, these studies define critical enzymatic control points through which genetic variation, diet and metabolic stress alter lipid handling and contribute to metabolic diseases.
Significance to patient care
When changes happen to how the body breaks down fat, it can be linked to many health conditions. Dr. Liu studies how the body makes, stores and uses fat. He also examines how disruptions in these processes contribute to obesity, diabetes, steatotic liver disease and cancer. By learning how cells and tissues maintain healthy fat balance, Dr. Liu's research helps advance new ways to prevent disease and develop better treatments.