Jingwen Liu, PhD, Principal Investigator, Research Service, Palo Alto VA hospital
Research Description: Over the past 22 years Dr. Liu has been directing a research program that seeks new therapeutic options to treat hyperlipidemia through molecular and cellular studies conducted in liver cells and various animal models. Hyperlipidemia is one underlying causal factors for developing diabetes. Among numerous accomplishments, Dr. Liu’s team has characterized a new cellular pathway that upregulates the liver low-density lipoprotein receptor (LDLR) transcription through a cholesterol-independent mechanism and demonstrated the effective cholesterol reduction in hyperlipidemic animals by activating this pathway. Furthermore, Dr. Liu’s laboratory has identified a novel post-transcriptional mechanism of LDLR gene that mediates the cholesterol-lowering effects of herbal medicine berberine as well as the medicinal plant goldenseal. In the last several years, PCSK9 has emerged as a new therapeutic target for treating hypercholesterolemia. PCSK9 is a key regulator of serum LDL-C metabolism by promoting the degradation of hepatic LDLR. Dr. Liu’s research in characterizing the transcriptional mechanism of PCSK9 has brought new insight for developing novel therapeutic approach to inhibit PCSK9 biosynthesis with a potential to improve the efficacy of current cholesterol-lowering drug statins for the management of hypercholesterolemia. Her group has long-standing, productive collaborations with members of the SDRC including Dr. Kraemer and Dr. Tsao.
Selected relevant publications (Stanford DRC members in BOLD):
1. Dong B, Kan CF, Singh AB and Liu J. High fructose diet downregulates long-chain acyl-CoA synthetase 3 expression in liver of hamsters via impairing LXR/RXR signaling pathway. J Lipid Res. 54:1241–1254, 2013.
2. 3. Kan CF, Singh AB, Stafforini DM, Azhar S, and Liu J. Arachidonic acid down regulates acyl-CoA synthetase 4 expression by promoting its ubiquitination and proteasomal degradation. J Lipid Res. 55: 1657–1667, 2014.
4. Singh AB, Kan CF, Shende V, Dong B, and Liu J. A novel posttranscriptional mechanism for dietary cholesterol-mediated suppression of liver LDL receptor expression. J Lipid Res. 55:1397-1407, 2014.
5. Dong B, Li H, Singh AB, Cao A, Liu J. Inhibition of PCSK9 transcription by berberine involves downregulation of hepatic HNF1 protein expression through ubiquitin-proteasome degradation pathway. J Biol Chem. 290:4047-4058, 2015
6. Dong B, Singh AB, Azhar S, Seidah NG, Liu J. High-fructose feeding promotes accelerated degradation of hepatic LDL receptor and hypercholesterolemia in hamsters via elevated circulating PCSK9 levels. Atherosclerosis. 239:364-374, 2015.
7. Kan CF, Singh AB, Dong B, Shende V, and Liu J. PPAR activation induces hepatic long-chain acyl-CoA synthetase 4 expression in vivo and in vitro. Biochim Biophys Acta. 1851:577-587, 2015
8. Shende V, Wu M, Singh AB, Dong B, Kan CF, and Liu J. Reduction of circulating PCSK9 and LDL-C levels by liver-specific knockdown of HNF1α in normolipidemic mice. J Lipid Res. 56:801-809, 2015