Research Summary

My research focuses on the molecular mechanisms underlying lung cancer and lung fibrosis. For many years my work primarily focused on proteases and adhesion receptors coordinate cell invasion and extracellular matrix remodeling, especially integrin signaling. I led the first discovery of the physical and functional connections between integrins and the key cell surface protease, plasminogen activator. After moving from Harvard to UCSF, I was committed to understanding and targeting the emerging relationship between hypoxia, EMT, and tissue remodeling during fibrogenesis and cancer progression. I pioneered the in vivo investigation of the role of epithelial mesenchymal transition (EMT) in pulmonary fibrosis and uncovered mechanistic insight as to how integrins and hypoxia regulate epithelial cell plasticity. In the past few years, I have been focusing on cell-based high throughput screen of TGFbeta1 inhibitors and identified small molecules that inactivate lysyl oxidase activity and selectively block TGFbeta1 responses in tumor cells and fibroblasts. These compounds greatly attenuated pulmonary fibrosis and blocked lung cancer metastasis in mouse disease models. I have led the efforts to the dissection of MOAs of the lead compounds and I am the main contributor to the pilot clinical study of the lead compound on blocking fibrotic biomarkers in patient lungs with Idiopathic Pulmonary Fibrosis (IPF). My future goal is to bring the most promising drug candidate that specifically blocks the TGFbeta1-induced collagen program in fibroblasts to the clinical arena.

Education

1988, B.Sc. in Pharmacy, Shanghai Medical University
1991, M.D. in Medicine, Shanghai Medical University
1991-1993, Research Assistant in Molecular Biology and Cell Biology, Shanghai Institute of Cell Biology, Academia Sinica
1993-1997, Postdoctoral Fellow in Medicine, Respiratory Division, Brigham and Womens Hospital, Harvard Medical School

Honors & Awards

  • 1983-1988
    College Dean's List (every year)
  • 1991
    Rong-Ling's Scholarship (the highest honor for exceptional graduating students)

Selected Publications

  • Wu, MP; Wei, Y; Li, YW; Mei, MZ. A Simple Procedure for Purification of Rat Hepatic Endothelial Lipase(HEL). Acta Biochemica et Biophycica sinica. 1989; 21:389-392
  • Wu, MP; Xu, PF; Wei, Y; Mei, MZ. A Study on the Metabolic Function of Rat Hepatic Endothelial Lipase(HEL). Acta Academiae Medicinae Shanghai. 1989; 16:126-130
  • Wu, MP; Wei, Y; Li, YW; Xu, PF; Mei, MZ. A Study on the Characteristics of Rat Hepatic Endothelial Lipase(HEL). Acta Academiae Medicinae Shanghai. 1989; 16:121-125
  • Zhu, YS; Wei, Y; Wen, ZP; Zhu, H; Song, HY. Tissue-type Plasminogen Activator (tPA) cDNA Expression Plasmid (containing SV40 Early Promoter) and its Transient Expression in Mammalian Cells. Acta Academiae Medicinae Shanghai. 1992; 19 (suppl): 21-23
  • Song, HY; Wei, Y; Zhu, YS; Wen, ZP; Zhu, H; Zhang, YL; Sun, CE. Tissue-type Plasminogen Activator (tPA) cDNA Expression Plasmid (containing hMT-IIA Promoter) and its Expression in Mammalian Cells. Acta Academiae Medicinae Shanghai. 1992; 19 (suppl):12-17
  • Wei, Y; Ni, ZM; Zhou, Y; Wu, L; Shi, LJ. The Study of Metaphasic Chromosome Pellicle. Shih Yen Sheng Wu Hsueh Pao. 1994; 27:505-513
  • Wei, Y; Waltz, DA; Rao, NK; Drumond, RJ; Rosenberg, S; Chapman, HA. Identification of the Urokinase Receptor as an Adhesion Receptor for Vitronectin. J. Biol. Chem. 1994; 269:32380-32388
  • Wei, Y; Lukashev, M; Simon, DI; Bodary, SI; Rosenberg, S; Doyle, M; Chapman, HA. Regulation of Integrin Function by the Urokinase Receptor. Science. 1996; 273:1551-1554
  • Simon, DI; Rao, NK; Xu, H; Wei, Y; Majdic, O; Ronne, E; Kobzik, L; Chapman, HA. Mac-1 (CD11b/CD18) and the Urokinase Receptor (CD87) Form a Functional Unit on Monocytic Cells. Blood. 1996; 88:3185-3194
  • Waltz, DA; Natkin, LR; Fujita, RM; Wei, Y; Chapman, HA. Plasmin and Plasminogen Activator Inhibitor Type I Promote Cellular Motility by Regulating the Interaction between the Urokinase Receptor and Vitronectin. J. Clin. Invest. 1997; 100:58-67
  • Wei, Y; Yang, XW; Liu, QM; Wilkins, JA; Chapman, HA. Role for Caveolin in beta1 Integrin and Urokinase Receptor-Mediated Cell Adhesion. J. Cell Biol. 1999; 144:1285-1294
  • Chapman, HA; Wei, Y; Simon, DI; Waltz, DA. Role of Urokinase Receptor and Caveolin in Regulation of Integrin Signaling. Invited review to Thrombosis and Haemostasis. 1999; 82: 291-7
  • Wei, Y; Simon, DI; Zhang, L; Rao, NK; Xu, H; Chen, Z; Liu, Q; Rosenberg, S; Chapman, HA. Identification of a Urokinase Receptor-Integrin Interaction Site: Promiscuous Regulator of Integrin Function. J. Biol. Chem. 2000; 275: 10228-34
  • Chapman, HA and Wei, Y. Protease Crosstalk with Integrins: the Urokinase Receptor Paradigm. Invited review to Thrombosis and Haemostasis. 2001; 86: 124-9
  • Wei, Y; Eble, JA; Wang, ZM; Kreidberg, JA; Chapman, HA. Urokinase Receptors Promote Beta1 Integrin Function Through Interactions with the Integrin Alpha3Beta1. Mol. Biol. Cell. 2001; 12: 2975-86
  • Kugler, MC; Wei, Y; Chapman, HA. Urokinase Receptor and Integrin Interactions. Curr. Pharm. Des. 2003; 9: 1565-74. Review
  • Zhang, F; Tom, CC; Ching, TT; Kugler, MC; Kreidberg, JA; Wei, Y; Chapman, HA. Distinct Ligand Binding Sites in Integrin Alpha3beta1 Regulate Matrix Adhesion and Cell-Cell Contact. J. Cell Biol. 2003; 163: 177-88 (Co-correspondence Author)
  • Wei, Y; Czekay, RP; Robillard, L; Kugler, MC; Zhang, F; Kim, KK; Xiong, JP; Humphries, MJ; Chapman, HA. Regulation of Alpha5Beta1 Integrin Conformation and Function by Urokinase Receptor Binding. J. Cell Biol. 2005; 168: 501-511 (Co-correspondence Author)

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