1. Research topics  

1. Immunologic aspects of human diseases including atherosclerosis and rheumatoid arthritis.

2. Role of tumor necrosis factor superfamily (TNFSF) and its receptors in immune-regulation.

3. Inflammation with emphasis on the role of adhesion molecules, pro-inflammatory cytokines, chemokines, matrix metalloproteinases (MMPs) and Tissue factor (TF).

4. Toll-like receptor mediated signaling and its role in human diseases

2. Research description

The research interest in our lab is immunologic aspects of human diseases including atherosclerosis and rheumatoid arthritis.

Atherosclerosis was originally considered as a disease caused by elevation of cholesterol/lipids. It is now considered as an inflammatory disease. Atherosclerosis starts with infiltration of circulating monocyte/lymphocytes into blood vessel wall. Monocytes uptake residual modified-LDL (low-density lipoprotein) and transform to foam cells. These foam cells are responsible for the fatty streak appearance, the hallmark of atherosclerosis. As the disease proceeds, residual smooth muscle cells starts migration and proliferation to form fibrous cap. Further accumulation of cholesterol/lipids and apoptotic/necotic death of cells leads to the formation of necrotic core. The full grown atherosclerotic plaques composed of fibrous cap and necrotic core. Atherogenic factors such as adhesion molecules, pro-inflammatory cytokines, chemokines, matrix metalloproteinases (MMPs) are involved in atherogenesis.

Rheumatoid arthritis is an autoimmune disease characterized by the activation of auto-reactive T cells and antibodies. Auto-reactive T cells coordinate inflammatory responses mediated by chondrocyte, B cells, and synoviocytes in the joint. Communications between these cells are possible through TNFSF and their receptor pair such as TNF-α, CD40/CD40L, and LTβ-LTβR. Activation of MMP is also responsible for the destruction of joint tissues.

Our lab focuses on the role of pro-inflammatory cytokines, adhesion molecules, chemokines, and matrix metalloproteinases in the pathogenesis of atherosclerosis and rheumatoid arthritis. Our research goal is to understand the interplay between the various cells and immune-mediators in the pathogenesis of these disease and to develope any possible therapeutic methods for the better treatment of these diseases.

3. Selected recent publications

Won-Jung Kim, Yoon-Joong Kang, Kyoungho Suk, Jeong-Euy Park, Byoung S. Kwon, and Won-Ha Lee. Comparative analysis of the expression patterns of various TNFSF/TNFRSF in atherosclerotic plaques. Imm. Inv. in press     

Eun Mi Bae, Won-Jung Kim, Kyoungho Suk, Young-Mo Kang, Jeong-Euy Park, Won Young Kim, Eun Mi Choi, Beom Kyu Choi, Byoung S. Kwon, and Won-Ha Lee (2008/1) Reverse signaling initiated from GITRL induces NF-kB activation through ERK in the inflammatory activation of macrophages. Mol. Imm. 45(2):523-533     PDF(2.02M)

McKinstry KK, Golech S, Lee WH, Huston G, Weng NP, Swain SL (2007/9) Rapid default transition of CD4 T cell effectors to functional memory cells. J Exp Med. 204(9):2199-211      PDF(5.46M)

Won-Jung Kim, Ho Kim, Kyoungho Suk, and Won-Ha Lee (2007/7) Macrophages Express Granzyme B in the Lesion Areas of Atherosclerosis and Rheumatoid Arthritis. Imm. Let. 111(1):57-65     PDF(15.5M)

Eunmi Bae, Won-Jung Kim, Young-Mo Kang, Kyoungho Suk, Eun-Mi Koh, Hoon-Suk Cha, Kwang-Sung Ahn, and Won-Ha Lee. (2007/6) Glucocorticoid-induced TNFR family-related protein (GITR) mediated macrophage stimulation induces cellular adhesion and cytokine expression in rheumatoid arthritis. Clin Exp Immunol, 148:410-418     PDF(664K)

Won-Jung Kim, Eun-Mi Bae, Yoon-Joong Kang, Hyung-Uk Bae, Su Hyung Hong, Joo Y. Lee, Jeong-Euy Park, Byoung S. Kwon, Kyoungho Suk, and Won-Ha Lee. (2006/10) Glucocorticoid-induced TNFR family-related protein (GITR) mediates inflammatory activation of macrophages that can destabilize atherosclerotic plaques. Immunology 119(3):421-429      PDF(878K)

Min-Young Lee, Won-Jung Kim, Yoon-Joong Kang, Young-Mi Jung, Young-Mo Kang, Kyoungho Suk, Jeong-Euy Park, Eun-Mi Choi, Beom-Kyu Choi, Byoung S. Kwon, and Won-Ha Lee. (2006/10) Z39Ig is expressed on macrophages and mediates inflammatory reactions in arthritis and atherosclerosis. J Leuk Biol 80(4):922-8 PDF(590K)

Jung-Hee Kim, Ji-Hye Jeong, Sung-Tak Jeon, Ho Kim, Jiyeon Ock, Kyoungho Suk, Sang-In Kim, Kyung-Sik Song, and Won-ha Lee (2006/6) Decursin inhibits induction of inflammatory mediators by blocking NF-kB activation in macrophages. Mol. Pharm. 2006;69(6):1783-90     PDF(416K)

Susan L. Swain, Javed N Agrewala, Deborah M. Brown, Sawn M. Kelley-Gibbs, Susanne Golech, Gail Huston, Stephen C. Jones, Cris Kamperschroer, Won-Ha Lee, K Kai McKintry, Eulogia Roman, Tara Strutt, Nan-ping Weng (2006) CD4+ T-cell memory: generation and multi-faceted roles for CD4+ T cells in protective immunity to influenza. Immunol Rev 2006;211:8-22.     PDF(388K)

Ho Kim, Won-Jung Kim, Sung-Tak Jeon, Eun-Mi Koh, Hoon-Suk Cha, Kwang-Sung Ahn, and Won-Ha Lee (2005/9) Cyclophilin A may contribute to the inflammatory processes in rheumatoid arthritis through inductionof matrix degrading enzymes and inflammatory cytokines from macrophages. Clin Imm, 116(3):217-24.     PDF(785K)

Dae Young Jung, Heasuk Lee, Bo-Young Jung, Jiyeon Ock, Myung-Shik Lee, Won-Ha Lee, Kyungho Suk (2005/5) TLR4, but not TLR2, signals auto-regulatory apoptosis of cultured microglia: a critical role of IFNbeta as a decision-maker. J. Imm. 174(10):6467-76.     PDF(488K)

Yoon-Joong Kang, Won-Jung Kim, Hyung-Uk Bae, Dong-Ik Kim, Yong Bok Park, Jeong-Euy Park, Byoung S. Kwon and Won-Ha Lee (2005/3) Involvement of TL1A and DR3 in induction of pro-inflammatory cytokines and matrix metalloproteinase-9 in atherogenesis. Cytokine 29(5):229-235.     PDF(615K)

Won-Jung Kim, Yoon-Joong Kang, Eun-Mi Koh, Kwang-Sung Ahn, Hoon-Suk Cha, Won-Ha Lee(2005/1). LIGHT is involved in the pathogenesis of rheumatoid arthritis by inducing the expression of pro-inflammatory cytokines and MMP-9 in macrophages. Immunology 114:272-279     PDF(838K)

Kim, W. J. and Lee, W. H (2004/8) LIGHT is expressed in foam cells and involved in destabilization of atherosclerotic plaques through induction of matrix metalloproteinase-9 and IL-8.  Immune Network 4:116-122.

 Lee JY, Zhou L, Youn HS, Weatherill AR, Tapping R, Feng L, Lee WH, Fitzgerald K, Hwang DH. (2004/4) Saturated fatty acid activates but polyunsaturated fatty acid inhibits toll-like receptor 2 dimerized with toll-like receptor 6 or 1. J Biol Chem. 279(17):16971-9      PDF(492K)

Se-Hwa Kim, Yoon-Joong Kang, Won-Jung Kim, Dong-Kyun Woo, Yoon Lee, Dong-Ik Kim, Yong Bok Park, Byoung S. Kwon, Jeong-Euy Park, and Won-Ha Lee (2004/4) TWEAK can induce pro-inflammatory cytokines and matrix metalloproteinase-9 in macrophages. Circ. J. 68(4):396-399.     PDF(440K)

Lee JY, Ye J, Gao Z, Youn HS, Lee WH, Zhao L, Sizemore N, Hwang DH (2003/9). Reciprocal modulation of TLR4-signaling pathways involving MyD88 and PI3K/AKT by saturated and polyunsaturated fatty acids. J Biol Chem. 278(39):37041-51.     PDF(565K) 

Joo Y. Lee, Anthony Plakidas, Won H. Lee, Anne Heikkinen, Prithiva Chanmugam, George Bray and Daniel H. Hwang. Differential modulation of Toll-like receptors by fatty acids : preferential inhibition by n-3 polyunsaturated fatty acids. J Lipid Res 2003;44:479-86     PDF(1,107K)

Won-Ha Lee, Se-Hwa Kim, Euy-Myoung Jeong, Yoon-Ho Choi, Dong-Ik Kim, Byung Boong Lee, Young S. Cho, Byoung S.Kwon, and Jeong-Euy Park. A novel chemokine, Leukotactin-1, induces chemotaxis, pro-atherogenic cytokines, and tissue factor expression in atherosclerosis. Atherosclerosis 2002;161:255-60 
PDF(222K)

Won-Ha Lee, Se-Hwa Kim, Yoon Lee, Byung Boong Lee, Byungsuk Kwon, Hebok Song, Byoung S. Kwon, and Jeong-Euy Park. TNFRSF14 is involved in atherogenesis by inducing pro-inflammatory cytokines and matrix metalloproteinases. Arterioscler. Thromb. Vasc. Biol. 2001; 21:2004-2010.      PDF(532K)

Won-Ha Lee, Tae Hong Hwang, Akinori Kimura, Seung Woo Park, Manatsu Satoh, Hirofumi Nishi, Haruhito Harada, Junji Toyama, Jeong-Euy Park. Different expressivity of the ventricular essential myosin light chain gene mutation in familial hypertrophic cardiomyopathy. Am Heart J. 2001; 141: 184-189.     PDF(242K)

Young-Gyu Ko, Heonyong Park, Taeho Kim, Joong-Won Lee, Sang Gyu Park, Wongi Seol, Jee Eun Kim, Won-Ha Lee, Se-Hwa Kim, Jeong-Euy Park, and Sunghoon Kim. A cofactor of tRNA synthase is secreted to upregulate proinflammatory genes J. Biol. Chem. 2001;276:23028-23033     PDF(2,104K)

Se-Hwa Kim, Won-Ha Lee, Byoung S. Kwon, Goo Taeg Oh, Yoon-Ho Choi, and Jeong-Euy Park.TNFRSF12 may Destabilizes Atherosclerotic Plaques by Inducing Matrix Metalloproteinases. Jpn Circ. J  2001;65:136-138 (Rapid communication)     PDF(328K)

Won-Ha Lee, Tae-Hong Hwang, Chul-Hong Kim, Goo Taeg Oh, Yoon-Ho Choi, and Jeong-Euy Park. Genetic factors associated with endothelial dysfunction affect the early onset of coronary artery disease in Korean males. Vascular Medicine 2001;6:103-8