Ying Wei, MD

Adjunct Professor

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
Postdoc, 1997 - Medicine, Harvard Medical School
MD, 1991 - Medicine, Shanghai Medical College of Fudan University
Publications
  1. Cohen ML, Brumwell AN, Ho TC, Garakani K, Montas G, Leong D, Ding VW, Golden JA, Trinh BN, Jablons DM, Matthay MA, Jones KD, Wolters PJ, Wei Y, Chapman HA, Jourdan Le Saux C. A fibroblast-dependent TGFß1/sFRP2 noncanonical Wnt signaling axis promotes epithelial metaplasia in idiopathic pulmonary fibrosis. The Journal of clinical investigation 2024. PMID: 38980870


  2. Jourdan Le Saux C, Ho TC, Brumwell AM, Kathiriya JJ, Wei Y, Hughes JB, Garakani K, Atabai K, Auyeung VC, Papa FR, Chapman HA. BCL-2 Modulates IRE1α Activation to Attenuate ER Stress and Pulmonary Fibrosis. American journal of respiratory cell and molecular biology 2023. PMID: 38117250


  3. Cohen ML, Brumwell AN, Ho TC, Montas G, Golden JA, Jones KD, Wolters PJ, Wei Y, Chapman HA, Le Saux CJ. A fibroblast-dependent TGFβ1/sFRP2 noncanonical Wnt signaling axis underlies epithelial metaplasia in idiopathic pulmonary fibrosis. bioRxiv : the preprint server for biology 2023. PMID: 37577522


  4. Wei Y, Dong W, Jackson J, Ho TC, Le Saux CJ, Brumwell A, Li X, Klesney-Tait J, Cohen ML, Wolters PJ, Chapman HA. Blocking LOXL2 and TGFβ1 signalling induces collagen I turnover in precision-cut lung slices derived from patients with idiopathic pulmonary fibrosis. Thorax 2021. PMID: 33472968


  5. Chapman HA, Wei Y, Montas G, Leong D, Golden JA, Trinh BN, Wolters PJ, Le Saux CJ, Jones KD, Hills NK, Foster E, Oldham JM, Linderholm AL, Kotak P, Decaris M, Turner S, Song JW. Reversal of TGFß1-Driven Profibrotic State in Patients with Pulmonary Fibrosis. The New England journal of medicine 2020. PMID: 32160670


  6. Wei Y, Kim TJ, Peng DH, Duan D, Gibbons DL, Yamauchi M, Jackson JR, Le Saux CJ, Calhoun C, Peters J, Derynck R, Backes BJ, Chapman HA. Fibroblast-specific inhibition of TGF-ß1 signaling attenuates lung and tumor fibrosis. The Journal of clinical investigation 2017. PMID: 28872461


  7. Xi Y, Kim T, Brumwell AN, Driver IH, Wei Y, Tan V, Jackson JR, Xu J, Lee DK, Gotts JE, Matthay MA, Shannon JM, Chapman HA, Vaughan AE. Local lung hypoxia determines epithelial fate decisions during alveolar regeneration. Nature cell biology 2017. PMID: 28737769


  8. Grove LM, Southern BD, Jin TH, White KE, Paruchuri S, Harel E, Wei Y, Rahaman SO, Gladson CL, Ding Q, Craik CS, Chapman HA, Olman MA. Urokinase-type plasminogen activator receptor (uPAR) ligation induces a raft-localized integrin signaling switch that mediates the hypermotile phenotype of fibrotic fibroblasts. The Journal of biological chemistry 2014. PMID: 24644284


  9. Xi Y, Tan K, Brumwell AN, Chen SC, Kim YH, Kim TJ, Wei Y, Chapman HA. Inhibition of epithelial-to-mesenchymal transition and pulmonary fibrosis by methacycline. American journal of respiratory cell and molecular biology 2014. PMID: 23944988


  10. Sennino B, Ishiguro-Oonuma T, Wei Y, Naylor RM, Williamson CW, Bhagwandin V, Tabruyn SP, You WK, Chapman HA, Christensen JG, Aftab DT, McDonald DM. Suppression of tumor invasion and metastasis by concurrent inhibition of c-Met and VEGF signaling in pancreatic neuroendocrine tumors. Cancer discovery 2012. PMID: 22585997


  11. Ulsamer A, Wei Y, Kim KK, Tan K, Wheeler S, Xi Y, Thies RS, Chapman HA. Axin pathway activity regulates in vivo pY654-ß-catenin accumulation and pulmonary fibrosis. The Journal of biological chemistry 2011. PMID: 22203675


  12. Duriseti S, Goetz DH, Hostetter DR, LeBeau AM, Wei Y, Craik CS. Antagonistic anti-urokinase plasminogen activator receptor (uPAR) antibodies significantly inhibit uPAR-mediated cellular signaling and migration. The Journal of biological chemistry 2010. PMID: 20501655


  13. Kim Y, Kugler MC, Wei Y, Kim KK, Li X, Brumwell AN, Chapman HA. Integrin alpha3beta1-dependent beta-catenin phosphorylation links epithelial Smad signaling to cell contacts. The Journal of cell biology 2009. PMID: 19171760


  14. Kim KK, Wei Y, Szekeres C, Kugler MC, Wolters PJ, Hill ML, Frank JA, Brumwell AN, Wheeler SE, Kreidberg JA, Chapman HA. Epithelial cell alpha3beta1 integrin links beta-catenin and Smad signaling to promote myofibroblast formation and pulmonary fibrosis. Volume 119 of Issue 1. The Journal of clinical investigation 2008. PMID: 19104148


  15. Tang CH, Hill ML, Brumwell AN, Chapman HA, Wei Y. Signaling through urokinase and urokinase receptor in lung cancer cells requires interactions with beta1 integrins. Journal of cell science 2008. PMID: 18940913


  16. Wei Y, Tang CH, Kim Y, Robillard L, Zhang F, Kugler MC, Chapman HA. Urokinase receptors are required for alpha 5 beta 1 integrin-mediated signaling in tumor cells. The Journal of biological chemistry 2006. PMID: 17145753


  17. Ghosh S, Johnson JJ, Sen R, Mukhopadhyay S, Liu Y, Zhang F, Wei Y, Chapman HA, Stack MS. Functional relevance of urinary-type plasminogen activator receptor-alpha3beta1 integrin association in proteinase regulatory pathways. The Journal of biological chemistry 2006. PMID: 16510444


  18. 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. The Journal of cell biology 2005. PMID: 15684035


  19. Zhang F, Tom CC, Kugler MC, Ching TT, Kreidberg JA, Wei Y, Chapman HA. Distinct ligand binding sites in integrin alpha3beta1 regulate matrix adhesion and cell-cell contact. The Journal of cell biology 2003. PMID: 14557254


  20. Kugler MC, Wei Y, Chapman HA. Urokinase receptor and integrin interactions. Current pharmaceutical design 2003. PMID: 12871068


  21. Wei Y, Eble JA, Wang Z, Kreidberg JA, Chapman HA. Urokinase receptors promote beta1 integrin function through interactions with integrin alpha3beta1. Molecular biology of the cell 2001. PMID: 11598185


  22. Simon DI, Wei Y, 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. The Journal of biological chemistry 2000. PMID: 10744708


  23. Wei Y, Yang X, Liu Q, Wilkins JA, Chapman HA. A role for caveolin and the urokinase receptor in integrin-mediated adhesion and signaling. The Journal of cell biology 1999. PMID: 10087270


  24. Waltz DA, Natkin LR, Fujita RM, Wei Y, Chapman HA. Plasmin and plasminogen activator inhibitor type 1 promote cellular motility by regulating the interaction between the urokinase receptor and vitronectin. The Journal of clinical investigation 1997. PMID: 9202057


  25. 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. PMID: 8874219


  26. Wei Y, Lukashev M, Simon DI, Bodary SC, Rosenberg S, Doyle MV, Chapman HA. Regulation of integrin function by the urokinase receptor. Science (New York, N.Y.) 1996. PMID: 8703217


  27. Wei Y, Waltz DA, Rao N, Drummond RJ, Rosenberg S, Chapman HA. Identification of the urokinase receptor as an adhesion receptor for vitronectin. The Journal of biological chemistry 1994. PMID: 7528215