Mentor for MD/PhD students, PhD students, Clinical Fellows
Lecture in Cancer Biology
TGFb signaling in cancer – TGFb is a multifunctional cytokine. TGFb suppresses tumor formation. Paradoxically, it also promotes cancer metastasis. We are using conditional transgenic/knockout mouse models to alter individual TGFb1 signaling components in head and neck epithelia and skin epidermis, in order to determine the mechanisms of TGFb effects on cancer, including TGFb signaling through pathways of Smad, MAPK, Rho, etc.
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.
TGFb signaling in wound healing – TGFb1 has both positive and negative effects on wound healing. We will utilize gene-switch transgenic mice to study the stage specific effects of TGFb signaling on wound healing.
TGFb1 in skin diseases – Our transgenic mice overexpressing the latent TGFb1 in the skin mimic psoriasis and fibrosis. We will study the molecular basis of TGFb1-induced diseases.
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Li AG, Wang D, Feng X, Wang XJ (2004). Latent TGFb1 overexpression in keratinocytes results in a severe psoriasis-like skin disorder. EMBO J, 23:1770-81.
Han G, Lu SL, Li AG, He W, Corless CL, Kulesz-Martin M, Wang XJ (2005). Distinct mechanisms of TGFb1-mediated epithelial-mesenchymal transition and metastasis during skin carcinogenesis. J Clin Invest, 115: 1714-1723
Lu SL, Herrington H, Reh D, Weber S, Bornstein S, Wang D, Li AG, Tang CF, Siddiqui Y, Nord J, Andersen P, Corless CL, Wang XJ (2006). Loss of transforming growth factor-b type II receptor promotes metastatic head-and-neck squamous cell carcinoma. Genes Dev, 20:1331-1342.
Han GW, Li AG, Liang YY, Owens P, He W, Lu S, Yoshimatsu Y, Wang D, ten Dijke P, Lin X, Wang XJ (2006). Smad7-induced b-catenin degradation alters epidermal appendage development. Dev Cell, 11, 301-312.
Hoot K, Lighthall J, Han G, Lu SL, Li AG, Ju W, Kulesz-Martin M, Bottinger E, Wang XJ (2008). Keratinocyte-Specific Smad2 ablation results in increased epithelial-mesenchymal transition during skin cancer formation and progression. J Clin Invest, 118:2722-32.
Owens P, Bazzi H, Engelking E, Han G, Christiano AM, Wang, XJ (2008). Smad4-dependent desmoglein-4 expression contributes to hair follicle integrity. Dev Biol, 322(1):156-66
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