Associate Research Professor
Department of Biochemistry
Boston University School of Medicine
Silvio Conte Building, Lab: K3; Office: K3
72 E. Concord Street
Boston, MA. 02118
MD, North China Coal Medical College, China
MS, Pathology, Zhejiang Medical University, China
Post-Doctor Fellow, Mallory Institute of Pathology, Boston City Hospital, and Department of Pathology, Boston University School of Medicine
Lysyl oxidase (LO), a copper-(Cu) dependent enzyme, oxidizes peptidyl lysine residues in substrates, e.g., collagen, elastin and histone H1, essential for organization and stabilization of the extracellular matrix (ECM) and the cell nucleus. Abnormal LO expression is implicated in various pathological states such as organ fibrosis, atherosclerosis, emphysema, carcinogenesis, etc. Thus, LO as an intra- and extracellular effector plays a critical role in pathogenesis of matrix diseases and cancers. Cadmium (Cd) is a toxic heavy metal widely used in industries affecting human health. In addition to the occupational contamination, cigarette smoke constitutes a major source of Cd exposure for humans since tobacco leaves naturally accumulate Cd. Chronic exposure of humans to Cd induces emphysema and lung cancers. Previous studies by this lab investigating the phenotype change from Cd sensitive to Cd resistant of rat lung fibroblasts illustrated that in comparison to other Cu binding proteins, LO was specifically downregulated at mRNA, protein and catalytic levels following long term-Cd exposure. To assess the transcriptional regulation of LO, we have cloned and characterized the 5’-flanking region of the rat LO gene. Current studies in this lab focuses on investigating Cd modulation of LO transcription and posttranscription in cell and animal model, thus enhancing our understanding of molecular mechanisms for the pathogenesis of lung cancer and emphysema induced by Cd, and providing the basis for developing protective and therapeutic strategies for these common lung diseases.
- Zhao, Y., L. Chen, S. Gao, P. Toselli, P. Stone and W. Li (2009). The critical role of the cellular thiol homeostasis in cadmium perturbation of the lung extracellular matrix. Toxicology
- Gao, S., Zhao, Y., Kong, L., Toselli, P., Chou, I-N., Stone, P. and Li, W. (2007). Cloning and characterization of the rat lysyl oxidase gene promoter: Identification of core promoter elements and functional nuclear factor I binding sites. J. Biol. Chem. 282, 25322-25337.
- Chou, D.K., Zhao, Y., Gao, S., Chou, I-N., Toselli, P., Stone, P. and Li, W. (2007). Perturbation of copper (Cu) homeostasis and expression of Cu-binding proteins in cadmium-resistant lung fibroblasts. Toxicol Sci. 99, 267-276.
- Zhao, Y., Gao, S., Chou, I-N., Toselli, P., Stone, P. and Li, W. (2006). Inhibition of the expression of lysyl oxidase and its substrates in cadmium-resistant rat fetal lung fibroblasts. Toxicol. Sci. 90, 478-489.
- Gao, S., Chen, K., Zhao, Y., Rich, C.B., Chen, L., Li, S.J., Toselli, P., Stone, P. and Li, W. (2005). Transcriptional and posttranscriptional inhibition of lysyl oxidase expression by cigarette smoke condensate in cultured rat fetal lung fibroblasts. Toxicol. Sci. 87, 197-203.
- Chen, L-J, Zhao, Y., Gao, S., Chou, I-N., Toselli, P., Stone, P. and Li, W. (2005). Downregulation of lysyl oxidase and upregulation of cellular thiols in rat fetal lung fibroblasts treated with cigarette smoke condensate. Toxicol. Sci. 83, 372-379.
- Li, W., Nugent, M.A., Zhao, Y., Chau, A.N., Li, S.L., Chou, I-N., Leu, G. and Kagan, H.M. (2003). Lysyl oxidase oxidizes basic fibroblast growth factor and inactivates its mitogenic potential. J. Cell. Biochem. 88, 152-164.
- Kagan, H.M. and Li, W. (2003). Lysyl oxidase: Properties, specificity and biological roles inside and outside of the cell. J. Cell. Biochem. 88, 660-672.
- Li, W., G. Liu, I. Chou and H.M. Kagan (2000). Hydrogen peroxide-mediated, lysyl oxidase-dependent chemotaxis of vascular smooth muscle cells. J. Cell. Biochem. 78, 550-557.
- Li, W., K. Nellaiappan, T. Strassmaier, L. Graham, K.M. Thomas and H.M. Kagan (1997). Localization and activity of lysyl oxidase within nuclei of fibrogenic cells. Proc. Natl. Acad. Sci. USA. 94, 12817-12822.
- Li, W., I-N. Chou, A Boak and H.M. Kagan (1995). Downregulation of lysyl oxidase in cadmium-resistant fibroblasts. Am. J. Respir. Cell Mol. Biol. 13, 418-425.