Xiao-Jing Wang
M.D., Ph.D.
Professor, Otolaryngology
Joint Professor, Cell and Developmental Biology
Role of transforming growth factor beta (TGFbeta) signaling in carcinogenesis, wound healing, skin development and diseases
TGFbeta is a multifunctional cytokine. We have developed inducible and keratinocyte-specific transgenic/knockout mouse models (gene-switch) that allow studying the functions of TGFbeta signaling in stratified epithelia. TGFbeta target genes can be identified from the screening of differentially expressed genes after the acute induction or deletion of TGFbeta signaling components. Ongoing projects are as follows:
1) TGFbeta signaling in carcinogenesis – Human cancers often overexpress TGFbeta1 ligand, but loose its signaling components including the receptors and downstream mediators, the Smads. We are using conditional transgenic/knockout mouse models to alter individual TGFbeta1 signaling components in head and neck epithelia and skin epidermis, in order to determine the effect of each molecule on tumor promotion and invasion.
2) Smads in skin development – We have generated transgenic/knockout mice in which individual Smad genes are deleted or overexpressed. These mice exhibited developmental defects of the skin. We are interested in the analysis of the underlying signaling transduction mechanisms.
3) TGFbeta signaling in wound healing – TGFbeta1 has both positive and negative effects on wound healing. We will utilize gene-switch transgenic mice to study the stage specific effects of TGFbeta signaling on wound healing.
4) TGFbeta1 in skin diseases – Our transgenic mice overexpressing the latent TGFbeta1 in the skin mimic psoriasis and fibrotic disorder. We will study the molecular basis of TGFb1-induced diseases.
Weeks BH, He W, Olson KL, Wang XJ (2001). Inducible expression of transforming growth factor beta1 (TGFbeta1) in papillomas causes rapid metastasis. Cancer Res, 61:7435-7443.
He W, Li AG, Wang D, Han S, Zheng B, Goumans M-J, ten Dijke P, Wang XJ (2002) Overexpression of Smad7 results in severe pathological alterations in multiple epithelial tissues. EMBO J, 21:2580-2590.
Cao T, He W, Roop DR, Wang XJ (2002). K14-GLp65 Transactivator induces transgene expression in embryonic epidermis. Genesis, 32:189-190.
Li AG, Koster MI, Wang XJ (2003). Role of TGFbeta signaling in skin development. Cytokine Growth Factor Rev, 14:99-111
Li AG, Wang D, Feng X, Wang XJ (2004). Latent TGFbeta1 overexpression in keratinocytes results in a severe psoriasis-like skin disorder. EMBO J, in press.