PHARMACOLOGY FACULTY
Selected Publications
  • Wei S-J, Williams J, Dang H, Darden TA, Betz BL, Humble MM, Chang F-M, Trempus CS, Johnson K, Cannon RE, and Tennant RW. (2008) Identification of a specific motif of the DSS1 protein required for proteasome interaction and p53 protein degradation. Journal of Molecular Biology, 383:693-712.
  • Betz BL, Wei S-J, Malarkey DE, Trempus CS, Humble MM, French JE, Tennant RW. (2008) Activated H-ras cooperates with disruption of p19Arf to induce gastrointestinal stromal tumors in mice. Gastroenterology (revised).
  • Qian L, Wei S-J, Zhang D, Wilson B, El-Benna J, Hong J-S, and Flood PM. (2008) Potent anti-inflammatory and neuroprotective effects of TGF ß1 are mediated through the inhibition of ERK and p47phox-Ser345 phosphorylation and translocation in microglia. Journal of Immunology, 181:660-668.
  • Qian L, Tan KS, Wei S-J, Wu H-M, Wilson B, Hong J-S, and Flood PM. (2007) Microglia-mediated neurotoxicity is inhibited by morphine through mu-opioid receptor independent reduction of NADPH oxidase activity. Journal of Immunology, 179:1198-1209.
  • Trempus CS, Dang H, Humble MM, Wei S-J, Gerdes M, Morris RJ, Bortner CD, Cotsarelis G, and Tennant RW. (2007) Comprehensive microarray transcriptome profiling of CD34-enriched mouse keratinocyte stem cells. Journal of Investigative Dermatology, 127:2904-2907.
  • Dang H, Trempus CS, Malarkey DE, Wei S-J, Humble MM, Morris RJ, and Tennant RW. (2006) Identification of genes and gene ontology processes critical to skin papilloma development in Tg.AC transgenic mice. Molecular Carcinogenesis, 45:126-140.
  • Li G, Cui G, Tzeng N-S, Wei S-J, Wang T, Block ML, and Hong J-S. (2005) Femtomolar concentrations of dextromethorphan protect mesencephalic dopaminergic neurons from inflammatory damage. FASEB Journal 19:489-496.
  • Zhang W, Qin L, Wang T, Wei S-J, Gao HM, Liu J, Wilson B, Liu B, Zhang W, Kim HC, Hong JS. (2005) 3-Hydroxymorphinan is neurotrophic to dopaminergic neurons and is also neuroprotective against LPS-induced neurotoxicity. FASEB Journal, 19:395-397.
  • Wei S-J, Trempus CS, Ali RC, Hansen LA, and Tennant RW. (2004) 12-O-tetradecanoylphorbol-13-acetate and UV radiation-induced nucleoside diphosphate protein kinase B mediates neoplastic transformation of epidermal cells. Journal of Biological Chemistry, 279:5993-6004.
  • Qin L, Liu Y, Wang T, Wei S-J, Block ML, Wilson B, Liu B, and Hong J-S. (2004) NADPH oxidase mediates LPS-induced neurotoxicity and proinflammatory gene expression in activated microglia. Journal of Biological Chemistry, 279:1415-1421.
  • Wei S-J, Trempus CS, Cannon RE, Botner CD, and Tennant RW. (2003) Identification of Dss1 as a 12-O-tetradecanoylphorbol-13-acetate-responsive gene expressed in keratinocyte progenitor cells, with possible involvement in early skin tumorigenesis. Journal of Biological Chemistry, 278:1758-1768.
  • Wei S-J, Ma YY, Lin YC, Lung JC, Chang TC, Whang-Peng J, Liu JM, Yang DM, Yang WK, Shen CY. (2000) PIK3CA as an oncogene in cervical cancer. Oncogene, 19:2739-2744.
  • Wei S-J, Chao Y, Shih Y-L, Yang D-M, Hung Y-M, and Yang WK. (1999) Involvement of Fas (CD95/APO-1) and Fas ligand in apoptosis induced by ganciclovir treatment of tumor cells transduced with herpes simplex virus thymidine kinase. Gene Therapy, 6:420-431.
Sung-Jen Wei, Ph.D.
 

Sung-Jen Wei

Assistant Professor
Ph.D., National Defense Medical Center (Taiwan)

Office: 956-393-6429
Email: WeiS3@uthscsa.edu

 

Keywords

keratinocyte stem cells, skin carcinogenesis, DSS1, RPN3/S3, ubiquitin-proteasome system, protein degradation, p53

 

Research Summary

The goals of our studies are to identify novel genes involved in early skin neoplastic development using a Tg.AC mouse model. This model possesses a v-Ha-ras transgene under the regulation of a fetal zeta-globin gene promotor which confers a unique phenotype of inducible skin papillomas with a high rate of progression to invasive squamous and spindle cell neoplasms. Evidence supports that keratinocyte stem cells (KSCs) residing in the hair follicle bulge region have long been thought to be a major carcinogen target which give rise to the latent neoplastic pool that clonally expand into cutaneous tumors. The candidate integrin alpha6+CD34+ KSCs were isolated using fluorescence-activated cell sorting from hyperplastic skin of TPA-treated Tg.AC mice skins and their gene expression was analyzed using a cDNA microarray. Interestingly, we have identified 11 genes whose expression changed significantly in the TPA-treated integrin alpha6+CD34+ KSCs. Two up-regulated genes, DSS1 and NDPK-B, have been identified and characterized as critical TPA-inducible genes expressed in KSCs, with possible involvement in early skin carcinogenesis. Recently, our laboratory is interested in the roles of DSS1 played by the ubiquitin-proteasome system in regulating protein degradation functions. We demonstrated that: 1) DSS1 binds to human proteasome via RPN3/S3 subunit of the 19S RP component of the proteasome; 2) the Asp/Glu-rich RPN3/S3-interacting motif of DSS1 regulates proteasome interaction and degradation of ubiquitin-conjugated substrates; 3) the interaction of DSS1 with RPN3/S3 is highly conserved throughout evolution from nematodes to humans; 4) the PCI domain of RPN3/S3 is required for binding to DSS1 and the proteasome; and 5) the DSS1/R3IM-proteasome complex is required for binding and targeting p53 for ubiquitin-mediated protein degradation via gankyrin/HDM2 pathway. Our laboratory is also interested in investigating: 1) if knock down of DSS1 will affect the cell growth and tumor transformation in vitro and in vivo; 2) the DSS1 functions in skin cancer using two-step regimen by conditionally knockout of DSS1 gene in mouse epidermis; 3) the transcriptional regulation by analyzing the binding sites of transcription factors in DSS1 gene promoter region.