(859) 217-1798 (Lab)
- 1990-1994: BS, Seoul National University College of Pharmacy, Seoul, Korea.
- 1994-1996: MS, Seoul National University College of Pharmacy, Seoul, Korea.
- 2000-2006: Ph.D. of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA.
- 2006-2011: Postdoctoral Fellow, Pathology & Laboratory Medicine, UCLA School of Medicine, Los Angeles, CA.
- 2011-2013: Assistant Researcher, Pathology & Laboratory Medicine, Atherosclerosis Research Unit, UCLA School of Medicine, Los Angeles, CA.
- 2013-present: Assistant Professor, Saha Cardiovascular Research Center, Pharmacology & Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY.
The oxidative stress and elevation of apoB-containing lipoproteins (VLDL and LDL particles) in the bloodstream is a risk factor for the development of atherosclerosis and metabolic diseases. My main research topic is to identify the mechanism of the development of hyperlipidemia-associated metabolic and cardiovascular diseases and find therapeutic targets to prevent or delay the development and progression of inflammatory and vascular diseases.
Accumulation of oxidized LDL particles (Ox-LDL) and oxidized phospholipids (Ox-PLs) in the vessel and circulation are significant events for the development of metabolic syndrome and atherosclerosis. Endothelial cells are particularly sensitive to the stimulation by Ox-PLs. We are interested in the gene regulatory and signaling mechanism of the Ox-PLs in the vascular endothelial cells for inflammatory responses. We test the hypothesis that the oxidized phospholipids employ both receptor and non-receptor pathways for inflammatory gene expression in the vascular endothelial cells. We adopt the primary culture of endothelial cells and hyperlipidemic mouse models (LDLR- or ApoE null) for the mechanistic study.
Most of the Ox-PLs are associated with lipoprotein(a) (Lp(a)) in circulation in humans; thus, the balance of synthesis and clearance of Lp(a) would be an essential factor for the healthy vessel. Oxidized phospholipids are exclusively cleared by the liver endothelial cells. We are testing a hypothesis that the liver sinusoidal endothelial cells (LSECs) are primarily responsible for the clearance of the Lp(a) in the human. The saturation and activation of the LSECs under moderate to severe oxidative stress environment would lead to hepatic inflammation via monocyte recruitment and concordant peripheral endothelial cell activation causing atherosclerosis.
As a newly developed project, we study the role of 'heparin-binding epidermal growth factor-like growth factor' (HB-EGF) signaling in regulating metabolic syndrome and disease phenotypes (atherosclerosis and fatty liver disease, for examples). The HB-EGF sensitive upregulated in the liver sinusoidal endothelial cells (LSECs) under oxidative stress regulates hepatic VLDL production and activation of the hepatic stellate cells (HSCs). We hypothesize that the upregulation of HB-EGF in the LSECs is a risk factor for the elevation of VLDL in circulation and induction of hepatic fibrosis. For the test of hypothesis, we are using endothelial cell-specific HB-EGF knockout mouse system and HB-EGF antisense oligonucleotide (ASO) with collaboration with Ionis Pharmaceutics. The ASO is preferentially uptaken by the LSECs, showed a remarkable downregulation of the circulatory lipid levels and protection against hepatic- and vascular inflammation in mouse models.
Role of heparin-binding EGF-like growth factor (HB-EGF) in oxidative stress-associated metabolic diseases.
Kim S, Subramanian V, Abdel-Latif A, Lee S. Metabolic Syndrome & Related Diseases 2020 Jan, Metab Syndr Relat Disord. 2020 Feb 20. doi: 10.1089/met.2019.0120. [Epub ahead of print]
Heparin-binding EGF-like growth factor (HB-EGF) antisense oligonucleotide protected against hyperlipidemia-associated atherosclerosis.
Kim S, Graham MJ, Lee RG, Yang L, Kim S, Subramanian V, Layne JD, Cai L, Temel RE, Shih D, Lusis AJ, Berliner JA, Lee S. Nutr Metab Cardiovasc Dis. 2019 Mar;29(3):306-315. doi: 10.1016/j.numecd.2018.12.006. Epub 2019 Jan 9.
Targeting hepatic heparin-binding EGF-like growth factor (HB-EGF) induces anti-hyperlipidemia leading to a reduction of angiotensin II-induced aneurysm development.
Kim S, Yang L, Kim S, Lee RG, Graham MJ, Berliner JA, Lusis AJ, Cai L, Temel RE, Rateri DL, Lee S.
PLoS One. 2017 Aug 9;12(8):e0182566. doi: 10.1371/journal.pone.0182566. eCollection 2017.
Fatty acid epoxyisoprostane E2 stimulates an oxidative stress response in endothelial cells.
Yan X, Lee S, Gugiu BG, Koroniak L, Jung ME, Berliner J, Cheng J, Li R.
Biochem Biophys Res Commun. 2014 Jan 31;444(1):69-74. doi: 10.1016/j.bbrc.2014.01.016. Epub 2014 Jan 14.
An epoxyisoprostane is a major regulator of endothelial cell function.
Zhong W, Springstead JR, Al-Mubarak R, Lee S, Li R, Emert B, Berliner JA, Jung ME.
J Med Chem. 2013 Nov 14;56(21):8521-32. doi: 10.1021/jm400959q. Epub 2013 Oct 31.
Role of phospholipid oxidation products in atherosclerosis.
Lee S, Birukov KG, Romanoski CE, Springstead JR, Lusis AJ, Berliner JA.
Circ Res. 2012 Aug 31;111(6):778-99. doi: 10.1161/CIRCRESAHA.111.256859. Review.
Evidence for the importance of OxPAPC interaction with cysteines in regulating endothelial cell function.
Springstead JR, Gugiu BG, Lee S, Cha S, Watson AD, Berliner JA.
J Lipid Res. 2012 Jul;53(7):1304-15. doi: 10.1194/jlr.M025320. Epub 2012 May 1.
Metalloproteinase processing of HBEGF is a proximal event in the response of human aortic endothelial cells to oxidized phospholipids.
Lee S, Springstead JR, Parks BW, Romanoski CE, Palvolgyi R, Ho T, Nguyen P, Lusis AJ, Berliner JA.
Arterioscler Thromb Vasc Biol. 2012 May;32(5):1246-54. doi: 10.1161/ATVBAHA.111.241257. Epub 2012 Mar 8.
A role for VEGFR2 activation in endothelial responses caused by barrier disruptive OxPAPC concentrations.
Birukova AA, Lee S, Starosta V, Wu T, Ho T, Kim J, Berliner JA, Birukov KG.
PLoS One. 2012;7(1):e30957. doi: 10.1371/journal.pone.0030957. Epub 2012 Jan 31.
Paraoxonase-2 modulates stress response of endothelial cells to oxidized phospholipids and a bacterial quorum-sensing molecule.
Kim JB, Xia YR, Romanoski CE, Lee S, Meng Y, Shi YS, Bourquard N, Gong KW, Port Z, Grijalva V, Reddy ST, Berliner JA, Lusis AJ, Shih DM.
Arterioscler Thromb Vasc Biol. 2011 Nov;31(11):2624-33. doi: 10.1161/ATVBAHA.111.232827.
Network for activation of human endothelial cells by oxidized phospholipids: a critical role of heme oxygenase 1.
Romanoski CE, Che N, Yin F, Mai N, Pouldar D, Civelek M, Pan C, Lee S, Vakili L, Yang WP, Kayne P, Mungrue IN, Araujo JA, Berliner JA, Lusis AJ.
Circ Res. 2011 Aug 19;109(5):e27-41. doi: 10.1161/CIRCRESAHA.111.241869. Epub 2011 Jul 7.
Systems genetics analysis of gene-by-environment interactions in human cells.
Romanoski CE, Lee S, Kim MJ, Ingram-Drake L, Plaisier CL, Yordanova R, Tilford C, Guan B, He A, Gargalovic PS, Kirchgessner TG, Berliner JA, Lusis AJ.
Am J Hum Genet. 2010 Mar 12;86(3):399-410. doi: 10.1016/j.ajhg.2010.02.002. Epub 2010 Feb 18.
A role for NADPH oxidase 4 in the activation of vascular endothelial cells by oxidized phospholipids.
Lee S, Gharavi NM, Honda H, Chang I, Kim B, Jen N, Li R, Zimman A, Berliner JA.
Free Radic Biol Med. 2009 Jul 15;47(2):145-51. doi: 10.1016/j.freeradbiomed.2009.04.013. Epub 2009 Apr 16.
Ox-PAPC activation of PMET system increases expression of heme oxygenase-1 in the human aortic endothelial cell.
Lee S, Li R, Kim B, Palvolgyi R, Ho T, Yang QZ, Xu J, Szeto WL, Honda H, Berliner JA.
J Lipid Res. 2009 Feb;50(2):265-74. doi: 10.1194/jlr.M800317-JLR200. Epub 2008 Aug 29.
Synthesis and biological evaluation of phosphonate derivatives as autotaxin (ATX) inhibitors.
Cui P, Tomsig JL, McCalmont WF, Lee S, Becker CJ, Lynch KR, Macdonald TL.
Bioorg Med Chem Lett. 2007 Mar 15;17(6):1634-40. Epub 2007 Jan 13.
OKL38 is an oxidative stress response gene stimulated by oxidized phospholipids.
Li R, Chen W, Yanes R, Lee S, Berliner JA.
J Lipid Res. 2007 Mar;48(3):709-15. Epub 2006 Dec 27.
Crystal structure analysis of phosphatidylcholine-GM2-activator product complexes: evidence for hydrolase activity.
Wright CS, Mi LZ, Lee S, Rastinejad F.
Biochemistry. 2005 Oct 18;44(41):13510-21.
Sphingosine kinase 2 is required for modulation of lymphocyte traffic by FTY720.
Kharel Y, Lee S, Snyder AH, Sheasley-O'neill SL, Morris MA, Setiady Y, Zhu R, Zigler MA, Burcin TL, Ley K, Tung KS, Engelhard VH, Macdonald TL, Pearson-White S, Lynch KR.
J Biol Chem. 2005 Nov 4;280(44):36865-72. Epub 2005 Aug 10.
Brown recluse spider (Loxosceles reclusa) venom phospholipase D (PLD) generates lysophosphatidic acid (LPA).
Lee S, Lynch KR.
Biochem J. 2005 Oct 15;391(Pt 2):317-23.