- (859) 218-1705 (Office)
- (859) 217-1798 (Lab)
- BBSRB B251
- 741 South Limestone
- Lexington, KY 40536-0509
1990. 3-1994. 2: B.S. College of Pharmacy, Seoul National University, Seoul, S. Korea.
1994. 3-1996. 2: M.S. College of Pharmacy, Seoul National University, Seoul, S. Korea.
2002. 9-2006. 5: Ph.D. of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA.
2006. 5-2011. 8: Postdoctoral Fellow, Pathology & Medicine-Cardiology, UCLA School of Medicine, Los Angeles, CA.
2011. 9-2013. 5: Assistant Researcher at Dept. Pathology & Laboratory Medicine, UCLA
School of Medicine, Los Angeles, CA.
2013. 6-present: Assistant Professor (Tenure-Track) at Saha Cardiovascular Research Center, Dept.
Pharmacology & Nutritional Sciences, University of Kentucky, Lexington, KY.
My research goal is to identify mechanism of the development of hyperlipidemia-associated cardiovascular diseases and find therapeutic targets to prevent or delay progress of the diseases. Hyperlipidemia-induced oxidative stress and accumulation of 'oxidized phospholipids' in the vessel wall are key events for the development of chronic inflammatory vascular diseases including atherosclerosis and aneurysm. These vascular diseases are accompanied by inflammatory cytokine overexpression and infiltration of monocytes and macrophages into the vessel wall. Oxidized phospholipids, as represented by Ox-PAPC, strongly activates vascular endothelial cells for the expression of proinflammatory and prothrombotic gene expressions. First, we test the hypothesis that the oxidized phospholipids employ both receptor and non-receptor cytosolic signaling and epigenetic modification for the induction of proinflammatory and prothrombotic gene expressions in the vascular endothelium. For study, we employ in vitro cell system and in vivo mouse model system (LDLR or ApoE null) with biochemical and epigenetics approaches to find key regulatory pathway and pharmacological targets. The elevation of ApoB-containing lipoproteins (VLDL and LDL) in the blood stream is a risk factor for the development of atherosclerosis and aneurysm. As second lab project, we study the role of 'heparin binding epidermal growth factor-like growth factor (HB-EGF)' signaling in regulating lipid balance in the liver and blood circulation. We hypothesize that HB-EGF is an unappreciated regulator of hepatic lipoprotein production/secretion and a potential target for lipid-lowering in circulation. HB-EGF targeting using anti-sense oligonucleotide (ASO) approach showed remarkable suppression of both hyperlipidemia and development of atherosclerosis and aneurysm in multiple mouse models. In further studies, we will identify HB-EGF signaling pathways for VLDL production in the liver. We employ liver-specific HB-EGF knockout liver cell system and in vitro liver cell line for this study.
Ongoing Research Support:
NIH-NHLBI K99/R00 HL105577 (Sangderk Lee, PI) 08/2011-07/2016
- Role of metalloproteinase-mediated EGFR signaling as a regulator of inflammatory responses to oxidized phospholipids in the vascular endothelium.
NIH-NIGM PILOT project, P20 GM103527 (Lisa Cassis, PI) 03/2016-02/2017
CENTER OF RESEARCH ON OBESITY AND CARDIOVASCULAR DISEASES
- Role of heparin binidng EGF-like growth factor (HB-EGF) in the development hyperlipidemia.
- Role: Co-Investigator
- Yan, X.;Lee, S.;Gugiu, B.G.;Koroniak, L.;Jung, M.E.;Berliner, J.;Cheng, J.;Li, R. "Fatty acid epoxyisoprostane E2 stimulates an oxidative stress response in endothelial cells." Biochemical and biophysical research communications 444, 1 (2014): 69-74. [PubMed Link] | [ Full text ]
- Zhong, W.;Springstead, J.R.;Al-Mubarak, R.;Lee, S.;Li, R.;Emert, B.;Berliner, J.A.;Jung, M.E. "An epoxyisoprostane is a major regulator of endothelial cell function." Journal of medicinal chemistry 56, 21 (2013): 8521-32. [PubMed Link] | [ Full text ]
- Lee, S.;Springstead, J.R.;Parks, B.W.;Romanoski, C.E.;Palvolgyi, R.;Ho, T.;Nguyen, P.;Lusis, A.J.;Berliner, J.A. "Metalloproteinase processing of HBEGF is a proximal event in the response of human aortic endothelial cells to oxidized phospholipids." Arteriosclerosis, thrombosis, and vascular biology 32, 5 (2012): 1246-54. [PubMed Link] | [ Full text ]
- Springstead, J.R.;Gugiu, B.G.;Lee, S.;Cha, S.;Watson, A.D.;Berliner, J.A. "Evidence for the importance of OxPAPC interaction with cysteines in regulating endothelial cell function." Journal of lipid research 53, 7 (2012): 1304-15. [PubMed Link] | [ Full text ]
- Lee, S.;Birukov, K.G.;Romanoski, C.E.;Springstead, J.R.;Lusis, A.J.;Berliner, J.A. "Role of phospholipid oxidation products in atherosclerosis." Circulation research 111, 6 (2012): 778-99. [PubMed Link] | [ Full text ]
- Birukova, A.A.;Lee, S.;Starosta, V.;Wu, T.;Ho, T.;Kim, J.;Berliner, J.A.;Birukov, K.G. "A role for VEGFR2 activation in endothelial responses caused by barrier disruptive OxPAPC concentrations." PloS one 7, 1 (2012): e30957. [PubMed Link] | [ Full text ]
- Kim, J.B.;Xia, Y.R.;Romanoski, C.E.;Lee, S.;Meng, Y.;Shi, Y.S.;Bourquard, N.;Gong, K.W.;Port, Z.;Grijalva, V.;Reddy, S.T.;Berliner, J.A.;Lusis, A.J.;Shih, D.M. "Paraoxonase-2 modulates stress response of endothelial cells to oxidized phospholipids and a bacterial quorum-sensing molecule." Arteriosclerosis, thrombosis, and vascular biology 31, 11 (2011): 2624-33. [PubMed Link] | [ Full text ]
- Romanoski, C.E.;Che, N.;Yin, F.;Mai, N.;Pouldar, D.;Civelek, M.;Pan, C.;Lee, S.;Vakili, L.;Yang, W.P.;Kayne, P.;Mungrue, I.N.;Araujo, J.A.;Berliner, J.A.;Lusis, A.J. "Network for activation of human endothelial cells by oxidized phospholipids: a critical role of heme oxygenase 1." Circulation research 109, 5 (2011): e27-41. [PubMed Link] | [ Full text ]
- Romanoski, C.E.;Lee, S.;Kim, M.J.;Ingram-Drake, L.;Plaisier, C.L.;Yordanova, R.;Tilford, C.;Guan, B.;He, A.;Gargalovic, P.S.;Kirchgessner, T.G.;Berliner, J.A.;Lusis, A.J. "Systems genetics analysis of gene-by-environment interactions in human cells." American journal of human genetics 86, 3 (2010): 399-410. [PubMed Link] | [ Full text ]
- Lee, S.;Gharavi, N.M.;Honda, H.;Chang, I.;Kim, B.;Jen, N.;Li, R.;Zimman, A.;Berliner, J.A. "A role for NADPH oxidase 4 in the activation of vascular endothelial cells by oxidized phospholipids." Free radical biology & medicine 47, 2 (2009): 145-51. [PubMed Link] | [ Full text ]
- Lee, S.;Li, R.;Kim, B.;Palvolgyi, R.;Ho, T.;Yang, Q.Z.;Xu, J.;Szeto, W.L.;Honda, H.;Berliner, J.A. "Ox-PAPC activation of PMET system increases expression of heme oxygenase-1 in human aortic endothelial cell." Journal of lipid research 50, 2 (2009): 265-74. [PubMed Link] | [ Full text ]
- Cui, P.;Tomsig, J.L.;McCalmont, W.F.;Lee, S.;Becker, C.J.;Lynch, K.R.;Macdonald, T.L. "Synthesis and biological evaluation of phosphonate derivatives as autotaxin (ATX) inhibitors." Bioorganic & medicinal chemistry letters 17, 6 (2007): 1634-40. [PubMed Link] | [ Full text ]
- Li, R.;Chen, W.;Yanes, R.;Lee, S.;Berliner, J.A. "OKL38 is an oxidative stress response gene stimulated by oxidized phospholipids." Journal of lipid research 48, 3 (2007): 709-15. [PubMed Link] | [ Full text ]
- Wright, C.S.;Mi, L.Z.;Lee, S.;Rastinejad, F. "Crystal structure analysis of phosphatidylcholine-GM2-activator product complexes: evidence for hydrolase activity." Biochemistry 44, 41 (2005): 13510-21. [PubMed Link] | [ Full text ]
- Lee, S.;Lynch, K.R. "Brown recluse spider (Loxosceles reclusa) venom phospholipase D (PLD) generates lysophosphatidic acid (LPA)." The Biochemical journal 391, Pt 2 (2005): 317-23. [PubMed Link] | [ Full text ]
- Kharel, Y.;Lee, S.;Snyder, A.H.;Sheasley-O'neill, S.L.;Morris, M.A.;Setiady, Y.;Zhu, R.;Zigler, M.A.;Burcin, T.L.;Ley, K.;Tung, K.S.;Engelhard, V.H.;Macdonald, T.L.;Pearson-White, S.;Lynch, K.R. "Sphingosine kinase 2 is required for modulation of lymphocyte traffic by FTY720." The Journal of biological chemistry 280, 44 (2005): 36865-72. [PubMed Link] | [ Full text ]