Wun-Shaing Wayne Chang, Ph.D.
National Institute of Cancer Research
EDUCATIONPh.D., Haematology and Biomedical Science, University of Cambridge, Cambridge, UK, 1995.
B.S., Marine Biology, Chinese Culture University, Taiwan, 1988
- Assistant Investigator, National Institute of Cancer Research, National Health Research Institutes, Taiwan (2006-2007)
- Assistant Investigator, President’s Laboratory, National Health Research Institutes, Taiwan (2001-2005)
- Postdoctoral Fellow, President’s Laboratory, National Health Research Institutes, Taiwan (1998-2000)
- Postdoctoral Research Associate, Department of Haematology, CambridgeUniversity, Cambridge, U.K. (1995-1997)
RESEARCH INTERESTSDr. Chang's laboratory is interested in the identification and characterization of protease and protease inhibitor genes involved in cancer invasion and metastasis. Of the collected 704 human protease/inhibitor genes, they have by far screened 246 genes and have identified 34 metastasis-suppressing and 32 metastasis-enhancing genes. The newly identified genes demonstrated evident differential expressions and significant effects on the migratory and invasive abilities of tumor cells. The catalytic mechanisms and molecular interactions of these proteases and protease inhibitors with target enzymes and substrates are now under investigation. Kinetic and structural characterizations will also be attempted to determine whether these proteases and protease inhibitors can serve as promising targets for therapeutic intervention of cancer invasion and metastasis.
RESEARCH ACTIVITIES & ACCOMPLISHMENTSDr. Chang's laboratory had successfully developed a genome-wide HPI (Human Proteases and Inhibitors) database. Through their patented in vitro invasion assay system, they were able to rapidly screen and determine an array of protease/inhibitor genes that may contribute to tumor metastasis. Notably, approximately half of the identified metastasis-suppressing genes belong solely to the serpin superfamily of serine protease inhibitors, with the entire SERPINB family members all possessing strong suppression effects on tumor cell migration and invasion. A series of potential therapeutic peptides corresponding to the reactive loop sequences of SERPINB proteins were synthesized and resulted in a drastically decrease of cell invasiveness. In addition, most members (i.e. KLK7, KLK11 and KLK13) of the kallikrein (KLK) serine protease family were found to significantly enhance but few (i.e. KLK8) could on the contrary inhibit cancer metastasis. Even more surprisingly, some protease inhibitors such as SPINK2 and SPINK4 were identified to vastly promote the invasive capability of tumor cells. Analyses using RT-PCR further demonstrated that the expression level of these genes is heavily associated with tumor metastasis. Taken together, these data not only provide beneficial information for the use of protease/inhibitor genes as potential biomarkers for prognosis and prediction of relapse in cancer patients, but also facilitate further research on these newly discovered metastasis-related protease and protease inhibitor genes.
- Chang WSW*, Chou RH, Wu CW and Chang JY. Human tissue kallikreins as prognostic biomarkers and as potential targets for anticancer therapy. Exp. Opin. Ther. Patents, 17:1227-1240, 2007. (* = Corresponding Author)
- Chen PY, Chang WSW*, Chou RH, Lai YK, Lin SC, Chi CY and Wu CW. Two non-homologous brain diseases-related genes, SERPINI1 and PDCD10, are tightly linked by an asymmetric bidirectionalpromoter in an evolutionarily conserved manner. BMC Mol. Biol, 8:2, 2007. (* = Corresponding Author)
- Sher YP, Chou CC, Chou RH, Wu HM, Chang WSW, Chen CH, Yang PC, Wu CW, Yu CL and Peck K. Human kallikrein 8 Suppresses cancer cell invasiveness to yield favorable clinical outcome in non-small cell lung cancer. Cancer Res, 66:11763-11770, 2006.
- Chou RH, Lin KC, Lin SC, Cheng JY, Wu CW and Chang WSW*. Cost-effective trapezoidal modified Boyden chamber with comparable accuracy to a commercial apparatus. BioTechniques, 37:724-726, 2004. (* = Corresponding Author)
- Chang WSW, Chang NT, Lin SC, Wu CW and Wu FYH. Tissue-specific cancer-related serpin gene cluster at human chromosome band 3q26. Gene. Chromosome Canc. 27:240-255, 2000.
- Chang WSW and Lomas DA. Latent ?1-antichymotrypsin: a molecular explanation for the inactivation of ?1-antichymotrypsin in chronic bronchitis and emphysema. J. Biol. Chem, 273:3695-3701, 1998.
- Chang WSW*, Whisstock J, Hopkins PCR, Lesk AM, Carrell RW and Wardell MR. Importance of the release of strand 1C to the polymerization mechanism of inhibitory serpins. Protein Sci, 6:89-98, 1997.(* = Corresponding Author)
- Taiwan Patent No. M240450 "A novel cell culture model for the in vitro invasion assay." Chang WSW, Lin KC, Wu CW; 2004.