Luyuan Li, Associate Professor
PhD, Cornell University, New York, 1988
Email: lil@upmc.edu
My lab is interested in the molecular mechanisms of vascular homeostasis. We recently discovered an endothelial cell-specific gene that we named vascular endothelial growth inhibitor (VEGI; TNFSF15). Our findings indicate that VEGI modulates the cell growth cycle and death of endothelial cells. Systemic administration of recombinant VEGI in animal models leads to eradication of tumor endothelial cells and inhibition of tumor growth. In addition, VEGI may play a role in the regulation of the function of dendritic cells, and the differentiation of endothelial progenitor cells from hematopoietic stem cells. We are studying the mechanism of VEGI action and the potential of this unique cytokine as an anticancer therapeutic agent.
Another project involves an endothelial cell receptor tyrosine kinase, Tie2, and its ligand, angiopoietin-1 (Ang1). The function of Ang1 is to modulate vascular branching, pericyte recruitment, and endothelial cell survival. We found that engineered high levels of Ang1 in tumor models led to stabilization of tumor neovasculature, which may have limited the otherwise continuous angiogenesis in the tumor and, consequently, given rise to inhibition of tumor growth. We are studying this new paradigm in the light of pericyte-endothelial cell interaction and tumor microenvironment.
Recent Publication
Hayes, AJ, Maisonpierre, P, Huang, WQ, McLeskey, S, Kern, F, Lippman, ME, and Li, LY. Expression and function of angiopoietin-1 in breast cancer. Brit. J. Cancer 83:1154-1160, 2000
Yu, JY, Tian, S, Metheny-Barlow, L, Chew, LJ, Hayes, A, Huang, WQ, Pan HG, Yu, GL, and Li, LY. Modulation of Endothelial Cell Growth Arrest and Apoptosis by Vascular Endothelial Growth Inhibitor. Circulation Res. 89:1161-1167, 2001
Tian, S, Hayes, AJ, Metheny-Barlow, L, and Li, LY. Stabilization of breast cancer xenograft tumor neovasculature by angiopoietin-1. Brit. J. Cancer 86:645-651, 2002
Chew, LJ, Pan, HG, Yu, J, Tian, S, Huang, WQ, Zhang, JY, Pang, S, and Li, LY. A novel secreted splice variant of vascular endothelial cell growth inhibitor. FASEB J, 16:742-4, 2002
Metheny-Barlow, LJ, Tian, S, Hayes, AJ, Li, LY. Direct chemotactic action of angiopoietin-1 on mesenchymal cells in the presence of VEGF. Microvascular Res. 68:221-230, 2004
Hou, W, Medynski, D, Wu, S, Lin, XL, Li, LY. VEGI-192, a New Isoform of TNFSF15, Specifically Eliminates Tumor Vascular Endothelial Cells and Suppresses Tumor Growth. Clinical Cancer Res. 11:5595-5602, 2005
Tian, F, Grimaldo, S, Mitssugu, F, Cutts, J, Vujanovic, NL, and Li, LY. The Endothelial Cell-Produced Anti-Angiogenic Cytokine Vascular Endothelial Growth Inhibitor (VEGI) Induces Dendritic Cell Maturation. J. Immunol. 179:3742-51, 2007
