Cardio-Metabolic Lipidology and Lipidomics

Lipids (fats or oils) are essential nutrients that act as both structural building blocks and signalling molecules in cells. Certain lipid changes, such as those induced by regular exercise, help maintain healthy metabolism, while others, often driven by poor diet or stress, accelerate ageing, trigger inflammation, and damage organs. Lipid imbalance is therefore a central driver of heart and blood vessel diseases and is closely linked to diabetes, obesity, and fatty liver. Beyond the familiar triglycerides and cholesterol, the human body contains more than 40,000 types of lipids — some beneficial, some harmful, and most still uncharacterised.

Our research focuses on three interconnected areas:

1. Understanding lipid (fat) science – We are exploring how lipids regulate energy production, stress responses, harmful factor release, and ageing process.

2. Transforming science into treatment – We are developing novel lipid-targeting therapies that enable weight even under sustained excess energy intake, and prevent vascular ageing in mid-life and mitigate age-related conditions in older adults.

3. Discovering early health-warning signs – We are identifying lipid biomarkers that predict individual response to lifestyle changes or medications, advancing personalised health strategies.

Lipids are a class of essential biomolecules, shaped by lifestyle and implicated in nearly all major diseases. With rapid advances in lipidomics and lipid imaging, lipids are now emerging as the “third dimension” of biomedical science, complementing genes and proteins in decoding the mystery of health and disease.

Despite the identification of over 45,000 lipid species, our knowledge has long been limited to a small subset, like triglycerides and cholesterol. A/Prof Jacob Qi and his team research centres on a fundamental question: which lipids safeguard health, and which promote ageing and disease? Using state-of-the-art technologies, including AI-powered big data analytics, his laboratory is dedicated to decoding which and how lipids change in age-related diseases. Team's goal is to identify druggable lipid targets and develop innovative strategies to predict, diagnose, prevent, and treat cardiovascular and metabolic diseases, ultimately enabling healthier, longer lives.

We have a number of research projects related to:

• Identifying key lipid triggers of blood vessel inflammation to unlock new anti-atherosclerosis strategies.
• Establishing the new concept of “Lipid control of blood vessel ageing”, opening the door to next-generation anti-ageing therapies.
• Engineering novel gene therapies to correct lipid imbalances and power up energy production in heart failure.
• Discovering lipid biomarkers that can “fortune-tell” who will or will not benefit from long-term lifestyle changes, such as diet and exercise.

Our research employs a broad range of approaches, including animal models of atherosclerosis, heart failure, vascular dementia, diabetes, obesity, and fatty liver; culture of primary vascular, heart, liver, and adipose cells; histology; molecular biology (adeno-associated virus, lentivirus, DNA, RNA, and protein analysis); lipidomics; machine learning–driven bioinformatics; advanced microscopy; and flow cytometry.

Prof. Jennifer Gamble – Centenary Institute, vascular biology

Prof. Geoff McCaughan – Centenary Institute and Royal Prince Alfred Hospital, clinical hepatology

Prof. Jennie Brand-Miller AO – University of Sydney, clinical nutrition

Distinguished Prof. Jing Sun – Charles Stuart University, AI-based bioinformatics

Prof. Anthony Don – University of Sydney, sphingolipid biology

Prof. Jane Hanrahan – University of Sydney, medicinal chemistry

Prof. Georges Grau – University of Sydney, extracellular vesicle biology

Prof. Laszek Lisowski – Children’s Medical Research Institute, AAV-based therapy

Prof. Kyle Hoehn – University of NSW, mitochondrial biology

A/Prof Ken Liu – Royal Prince Alfred Hospital, clinical hepatology

A/Prof Carlo Pulitano – Royal Prince Alfred Hospital, clinical hepatology

Dr Renjing Liu – Victor Chang Cardiac Research Institute, atherosclerosis

Prof Rob Yang – UT Health, US, phospholipid and sterol lipid biology

Prof Shubiao Zhang – Dalian Minzu University, China, lipid biomaterials

Prof Pingsheng Liu – University of Chinese Academy of Science, China, biophysics

Aji G, Huang Y, Ng ML, Wang W, Lan T, Li M, Li Y, Chen Q, Li R, Yan S, Tran C, Burchfield JG, Couttas TA, Chen J, Chung LH, Liu D, Wadham C, Hogg PJ, Gao X, Vadas MA, Gamble JR, Don AS, Xia P, Qi Yanfei. (2020). Regulation of hepatic insulin signaling and glucose homeostasis by sphingosine kinase 2. Proceedings of the National Academy of Sciences of USA (PNAS). 117: 24434-24442. (Yanfei, senior author).

Jiang YC, Lai K, Muirhead RP, Chung LH, Huang Y, James E, Liu XT, Wu J, Atkinson FS, Yan S, Fogelholm M, Raben A, Don AS, Sun J, Brand-Miller JC, Qi Yanfei. (2024). Deep serum lipidomics identifies evaluative and predictive biomarkers for individualized glycemic responses to successful weight loss: a PREVIEW sub-study. The American Journal of Clinical Nutrition. 120(4): 864-878. (Yanfei, senior author).

Liu XT, Huang Y, Liu D, Jiang YC, Zhao M, Chung LH, Han XD, Zhao Y, Chen J, Coleman P, Ting KK, Tran C, Su Y, Dennis CV, Bhatnagar A, Liu K, Don AS, Vadas MA, Gorrell MD, Zhang S, Murray M, Kavurma MM, McCaughan GW, Gamble JR, Qi Yanfei. (2024). Targeting the SphK1/S1P/PFKFB3 axis suppresses hepatocellular carcinoma progression by disrupting glycolytic energy supply that drives tumor angiogenesis. Journal of Translational Medicine. 22: 43. (Yanfei, senior author).

Liu XT, Chung LH, Liu D, Chen J, Huang Y, Teo JD, Han XD, Zhao Y, Guan FHX, Tran C, Lee JY, Couttas TA, Liu K, McCaughan GW, Gorrell MD, Don AD, Zhang S, Qi Yanfei. (2022). Ablation of sphingosine kinase 2 suppresses fatty liver-associated hepatocellular carcinoma via downregulation of ceramide transfer protein. Oncogenesis. 11:67. (Yanfei, senior author).

Wang H*, Ma Q*, Qi Yanfei, Dong J, Du X, Rae J, Wang J, Wu WF, Brown AJ, Parton RG, Wu JW, Yang H. (2019). ORP2 delivers cholesterol to the plasma membrane in exchange for phosphatidylinositol 4, 5-biphosphate (PI(4,5)P2). Molecular Cell. 73: 458-473. (Yanfei, co-first author).

Pagac M*, Cooper DE*, Qi Yanfei, Lukmantara1 IE, Mak HY, Wu Z, Tian Y, Liu Z, Lei M, Du X, Ferguson C, Kotevski D, Sadowski P, Chen W, Boroda S, Harris TE, Liu G, Parton RG, Coleman RA, Huang X, Yang H. (2016). SEIPIN regulates lipid droplet expansion and adipocyte development through modulating the activity of glycerol-3-phosphate acyltransferase. Cell Reports. 17: 1546-1559. (Yanfei, co-first author).

Qi Yanfei, Kapterian TS, Du X, Fei W, Zhang Y, Dawes IW, Yang H. (2016). CDP-diacylglycerol synthases regulate the growth of lipid droplets and adipocyte development. Journal of Lipid Research. 57: 767-780.

Holm A, Graus MS, Wylie-Sears J, Tan JWH, Alvarez-Harmon M, Borgelt L, Nasim S, Chung LH, Jain A, Sun M, Sun, Brouillard P, Lekwuttikarn R, Qi Yanfei, Teng J, Vikkula M, Kozakewich H, Mulliken JB, Francois M, Bischoff J. (2025). An endothelial SOX18-mevalonate pathway axis enables repurposing of statins for infantile hemangioma. Journal of Clinical Investigation. 25: e179782.

Wang Z, Ma W, Fu X, Qi Yanfei, Zhao Y, Zhang S. (2023). Development and applications of mRNA treatment based on lipid nanoparticles. Biotechnology Advances. 65: 108130.

Zhang S, Xu Y, Xie C, Ren L, Wu G, Yang M, Wu X, Tang M, Hu Y, Li Z, Yu R, Liao X, Mo S, Qi Yanfei, Song L, Li J. (2021). Targeting RNF219/α-catenin/LGALS3 axis inhibits hepatocellular carcinoma bone metastasis and associated skeletal complications. Advanced Science. 8: 2001961.