Research Interests:
Research in the Wang laboratory focuses on the structure and function of heparan sulfate in vasculature and cancer cells. Heparan sulfate is an abundant glycan found on the cell surface and in the extracellular matrix. In vitro studies have observed that heparan sulfate can interact with growth factors, growth factor binding proteins, extracellular proteases, protease inhibitors, chemokines, morphogens, and cell adhesive proteins to mediate cell differentiation, proliferation, migration, blood coagulation, lipid metabolism, and leukocyte trafficking. However, the relationship between heparan sulfate’s structure and function, and the underlying cellular and molecular mechanism of the actions in vivo, are largely unknown. By using techniques, including conditional mouse gene targeting, embryonic stem (ES) cell differentiation, primary cell culture, and animal models, the Wang lab is aiming to understand the roles and underlying molecular mechanisms of heparan sulfate in vascular development, blood coagulation and tumorigenesis, and to develop novel approaches to cure the related pathological conditions.
Publications since 2002:
Zhang B., Dietrich U.M., Geng J.G., Bicknell R., Esko J.D., and L.C. Wang. 2009. Repulsive axon guidance molecule Slit3 is a novel angiogenic factor. Blood In press.
Lawrence R., Olson S.k., Steele R.E., Wang L.C., Warrior R., Cummings R.D. and J.D. Esko. 2008. Evolutionary differences in glycosaminoglycan fine structure detected by quantitative glycan reductive isotope labeling. J Biol Chem 283(48):33674-84.
Schuksz M., M.M. Fuster, J.R. Brown, B.E. Crawford, D.P. Ditto, R.Lawrence, C.A. Glass, L.C. Wang, U. Tor and J.D. Esko. 2008. Surfen, a small molecule antagonist of heparan sulfate. Proc Natl Acad Sci USA 105(35):13075-80.
Cai C.L.*, J.C. Martin*, Y. Sun*, L. Cui, L.C. Wang, K. Ouyang, L. Yang, L. Bu, X. Liang, X. Zhang, W.B. Stallcup, C.P. Denton, A. McCulloch, J. Chen and S.M. Evans. 2008. A myocardial lineage derives from Tbx18 epicardial cells. Nature 354(7200):104-8. (*, co-first author).
Borsig L.*, L.C. Wang*, M.C. Cavalcante, L. Cardilo-Reis, P.L. Ferreira, P.A. Mourao, J.D. Esko, and M.S. Pavao. 2007. Selectin-blocking activity of a fucosylated chondroitin sulfate glycosaminoglycan from sea-cucumber: Effect on tumor metastasis and neutrophil recruitment. J Biol Chem 282(20):14984-91.(*, co-first author).
Fuster M.M., L.C. Wang, J. Castagnola, L. Sikora, K. Reddi, P.H. Lee, K.A. Radek, M. Schuksz, J.R. Bishop, R.L. Gallo, P. Sriramaro, and J.D. Esko. 2007. Genetic alteration of endothelial heparan sulfate selectively inhibits tumor angiogenesis. J Cell Biol 177:539-549.
Macarthur J.M., J.R. Bishop, K.I. Stanford, L.C. Wang, A. Bensadoun, J.L. Witztum, and J.D. Esko. 2007. Liver heparan sulfate proteoglycans mediate clearance of triglyceride-rich lipoproteins independently of LDL receptor family members. J Clin Invest 117(1): 153-164.
Wang, L.C., M.M. Fuster, P. Sriramarao, and J.D. Esko. 2005. Endothelial deficiency of heparan sulfate impairs L-selectin and chemokine mediated neutrophil trafficking during inflammatory responses. Nat Immunol 6: 902-910.
Rele, S.M., W. Cui, L.C. Wang, S. Hou, G. Barr-Zarse, D. Tatton, Y. Gnanou, J.D. Esko, and E.L. Chaikof. 2005. Dendrimer-like PEO glycopolymers exhibit anti-inflammatory properties. J Am Chem Soc 127: 10132-10133.
Tang, N., L.C. Wang, J.D. Esko, F.J. Giordano, Y. Huang, H. Gerber, N. Ferrara, and R.S. Johnson. 2004. Loss of HIF-1α in endothelial cells disrupts a hypoxia-driven VEGF autocrine loop necessary for tumorigenesis. Cancer Cell 6: 485-495.
Bobardt, M.D., P. Salmon, L.C. Wang, J.D. Esko, D. Gabuzda, M. Fiala, D. Trono, B. Van der Schueren, G. David, and P.A. Gallay. 2004. Contribution of proteoglycans to human immunodeficiency virus type 1 brain invasion. J Virol 78: 6567-6584.
Fuster, M.M., J.R. Brown, L.C. Wang, and J.D. Esko. 2003. A disaccharide precursor of sialyl Lewis X inhibits the metastatic potential of tumor cells. Cancer Res 63: 2775-2781.
Wang, L.C., J.R. Brown, A. Varki, and J.D. Esko. 2002. Heparin’s anti-inflammatory effects require glucosamine 6-O-sulfation and are mediated by blockade of L- and P-selectins. J Clin Invest 110: 127-136.
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