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Research in Lipid Sciences
Dr. Liqing Yu

Liqing Yu, MD PhD

Assistant Professor of Pathology (Lipid Sciences)
Tel: (336) 716-0920
Fax: (336) 716-6279
lyu@wfubmc.edu

Education:
  • Undergraduate: Hubei Medical University at Xianning, China, MD, 1985
  • Postgraduate: The Third Military Medical University, China, MS in Pathology 1988; Chinese Academy of Medical Sciences & Peking Union Medical University, China, PhD 1995
  • Fellowships: University of Alberta, Canada, 1996-98; University of Texas Southwestern Medical Center at Dallas, 1998-2000
Interests:
  • Teaching: Molecular Pathobiology, Gene-targeting and Transgenics, ATP-binding Cassette (ABC) Transporter Biology
  • Research: Sterol trafficking and metabolism, Application of transgenics and gene-targeting technology in biomedical research 
Current Research: Molecular Pathobiology of Sterol Trafficking and Esterification

The absorption, de novo biosynthesis and excretion of cholesterol are highly regulated in mammals. Deregulation of these pathways is related to pathogenesis of atherosclerotic diseases. Recently, the Niemann-Pick C1 Like 1 (NPC1L1) protein was found implicated in cholesterol absorption and the disruption of this gene in mice led to a dramatic reduction in fractional absorption of dietary cholesterol. However, how this gene mediates cholesterol absorption is largely unknown. In order to address this question, a series of cell biology and biochemical experiments are to be performed in our lab using cloned human NPC1l1 gene.

Also the intracellular machinery determining the metabolic fate of absorbed cholesterol in enteroctyes and hepatocytes are not clear. One pathway being extensively studied is cholesterol esterication by acyl CoA:cholesterol acyltransferase 2 (ACAT2) that esterifies free cholesterol (FC) to form cholesteryl ester (CE) in intestine and liver. On the other hand, two ABC half transporters ABCG5 and ABCG8 function as a heterodimer that can promote FC excretion from liver and probably from intestine as well. These three genes are exclusively expressed in hepatocytes and enterocytes. Depletion of ACAT2 in mice lowers intestinal cholesterol absorption and prevents atherosclerosis, whereas disruption of ABCG5/8 leads to accumulation of cholesterol on high cholesterol diet, and to sitosterolemia with which patients develop premature atherosclerotic artery disease. Based on their opposite effects on cholesterol absorption and atherogenesis, ACAT2 and ABCG5/8 may coordinate these important pathophysiologic processes. Our lab is crossing mice over-expressing or lacking ABCG5/8 to mice expressing no ACAT2 to study the crosstalk of ACAT2 and ABCG5/8 in the process of trafficking and esterification of various sterols including cholesterol and plant-derived sterols such as sitosterol, campesterol and stigmasterol.

Furthermore, the Cre/LoxP methodology will be employed to generate liver- and intestine-specific knockout mice so that the relative importance of these genes in sterol trafficking in the two tissues could be differentiated. 

Recent Publications:

Brown JM, Chung S, Das A, Shelness GS, Rudel LL, Yu L. CGI-58 facilitates the mobilization of cytoplasmic triglyceride for lipoprotein secretion in hepatoma cells. J Lipid Res. 2007 Oct;48(10):2295-305.

Temel RE, Tang W, Ma Y, Rudel LL, Willingham MC, Ioannou YA, Davies JP, Nilsson LM, Yu L. Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe. J Clin Invest. 2007 Jul;117(7):1968-78.

Tang W, Ma Y, Yu L. Plasma cholesterol is hyperresponsive to statin in ABCG5/ABCG8 transgenic mice. Hepatology. 2006 Nov;44(5):1259-66.

Yu L, Bharadwaj S, Brown JM, Ma Y, Du W, Davis MA, Michaely P, Liu P, Willingham MC, Rudel LL.  Cholesterol-regulated translocation of NPC1L1 to the cell surface facilitates free cholesterol uptake. J Biol Chem. 2006 Mar 10;281(10):6616-24.

Langheim S, Yu L, von Bergmann K, Lutjohann D, Xu F, Hobbs HH, Cohen JC. ABCG5 and ABCG8 require MDR2 for secretion of cholesterol into bile. J Lipid Res. 2005 Aug;46(8):1732-8.

Yu L, von Bergmann K, Lutjohann D, Hobbs HH, Cohen JC. Ezetimibe normalizes metabolic defects in mice lacking ABCG5 and ABCG8. J Lipid Res. 2005 Aug;46(8):1739-44.

Yu L, Gupta S, Xu F, Liverman AD, Moschetta A, Mangelsdorf DJ, Repa JJ, Hobbs HH, Cohen JC. Expression of ABCG5 and ABCG8 is required for regulation of biliary cholesterol secretion. J Biol Chem. 2005 Mar 11;280(10):8742-7.

Wilund KR, Yu L, Xu F, Vega GL, Grundy SM, Cohen JC, Hobbs HH. No association between plasma levels of plant sterols and atherosclerosis in mice and men. Arterioscler Thromb Vasc Biol. 2004 Dec;24(12):2326-32.

Yang C, Yu L, Li W, Xu F, Cohen JC, Hobbs HH. Disruption of cholesterol homeostasis by plant sterols. J Clin Invest. 2004 Sep;114(6):813-22.

Wilund KR, Yu L, Xu F, Hobbs HH, Cohen JC. High-level expression of ABCG5 and ABCG8 attenuates diet-induced hypercholesterolemia and atherosclerosis in Ldlr-/- mice. J Lipid Res. 2004 Aug;45(8):1429-36.

Yu L, Cao G, Repa J, Stangl H. Sterol regulation of scavenger receptor class B type I in macrophages. J Lipid Res. 2004 May;45(5):889-99.

Yu L, von Bergmann K, Lutjohann D, Hobbs HH, Cohen JC. Selective sterol accumulation in ABCG5/ABCG8-deficient mice. J Lipid Res. 2004 Feb;45(2):301-7.

Graf GA, Yu L, Li WP, Gerard R, Tuma PL, Cohen JC, Hobbs HH. ABCG5 and ABCG8 are obligate heterodimers for protein trafficking and biliary cholesterol excretion. J Biol Chem. 2003 Nov 28;278(48):48275-82.

Yu M, Gu SM, Zhou L, Zhao GF, Yu LQ, Zhang H, She MP. [Molecular basis of preventive effect of human apolipoprotein-1 on murine vascular smooth muscle cell proliferation and lipid deposition induced by oxidized low density lipoprotein. Zhonghua Yi Xue Za Zhi]. Natl Med J China 2003 Mar 25;83(6):494-7. Chinese.

Yu L, York J, Von Bergmann K, Lutjohann D, Cohen JC, Hobbs HH. Stimulation of cholesterol excretion by the liver X receptor agonist requires ATP-binding cassette transporters G5 and G8. J Biol Chem 2003 May 2;278(18):15565-15570.

Hobbs HH, Graf GA, Yu L, Wilund KR, Cohen JC. Genetic defenses against hypercholesterolemia. Cold Spring Harb Symp Quant Biol. 2002;67:499-505. Review.

Stangl H, Graf GA, Yu L, Cao G, Wyne K. Effect of estrogen on scavenger receptor BI expression in the rat. J Endocrinol. 2002 Dec;175(3):663-72.

Yu L, Hammer RE, Li-Hawkins J, Von Bergmann K, Lutjohann D, Cohen JC, Hobbs HH. Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion. Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16237-42.

Yu L, Li-Hawkins J, Hammer RE, Berge KE, Horton JD, Cohen JC, Hobbs HH. Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol. J Clin Invest. 2002 Sep;110(5):671-80.

Berge KE, Tian H, Graf GA, Yu L, Grishin NV, Schultz J, Kwiterovich P, Shan B, Barnes R, Hobbs HH. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science. 2000 Dec 1;290(5497):1771-5.

She M, Li H, Yu L, Gu S, Wang Z. Inhibition of intimal lipid deposition in human apolipoprotein A1 transgenic mice. Clin Exp Pharmacol Physiol. 1999 Oct;26(10):833-4.

Walkey CJ, Yu L, Agellon LB, Vance DE. Biochemical and evolutionary significance of phospholipid methylation. J Biol Chem. 1998 Oct 16;273(42):27043-6.

She MP, Yu L. Advances in the pathogenesis of atherosclerosis. Chinese Med J. 1997; 110: 14-21. [Review] [58 refs].

Yu L, She MP. Serum amyloid protein A - a new kind of apolipoproteins: ApoSAA. Chinese J Pathol. 1995; 24: 113-115.

Yu L, Qiu YF. Effects of butyric acid on the growth, cell cycle, and morphology of human lung cancer cells. Acta Acad Med Militaris Tertiae 1991;13: 5-10.

Qiu YF, Yu L. Quantitative analysis of butyric acid-induced nuclear ultrastructural alterations in cells of human lung giant cell carcinoma in vitro. J Med Coll. 1991; PLA 6: 166-169.