1. Esophageal carcinoma is one of the leading causes of death in Taiwan. The combination of chemotherapeutic agents with radiotherapy enhance the therapeutic efficacy by ablation the survival mechanism, i.e. cause massive apoptosis, of esophageal carcinoma. However, survival signals, i.e. production of IGF-1 and EGF in esophageal carcinoma cells, cause the cancer cells to escape from apoptosis. We are interested in investigating which signaling pathway is responsible for the IGF-1R and EGFR survival signal in esophageal carcinoma, by using various chemical signaling blockers, dominant negative mutants, and shRNA to narrow down the IGF-1 and EGF-mediated survival signal in esophageal carcinoma. The identified pathway will be used as a template to address which signaling components are important for IGF-1R and EGFR induced survival signals in esophageal carcinoma. Recently, we focus on two IGF-1 regulated anti-apoptosis molecules, aurora A, survivin and XIAP. The roles of the two genes in IGF-1R mediated survival pathway are under investigation.
2. To recapitulate the molecular events underlying tumor metastasis and to uncover a series of therapeutic targets for esophageal squamous cell carcinoma, we employed Affymetrix microarray profiling to delineate the molecular portrait of esophageal carcinoma specimens. Using these microarray datasets, transformation of the gene expression signatures into protein network, we identification a set of genes which could serve as the minimal discriminators for esophageal carcinoma. Within these genes, TGFBI was chose for further study. Currently, we are analyzing the association and the functions of this gene in esophageal carcinoma metastasis.
3. Cleft lip/palate is one of the most common congenital diseases in Taiwan, and van der Woude syndrome is the most important syndrome in cleft lip/palate. The mutation of IRF6 gene causes the van der Woude syndrome, thus IRF6 is a good candidate gene for studying the mechanisms of formation of cleft lip/palate. We try to understand the molecular mechanisms of IRF6 on the palate shelves fusion by organ culture. And the target genes regulated by IRF6 in palate epithelial cells during palate formation also will be identified. Our goal is to understand the molecular mechanism of mutated IRF6 on the formation of cleft palate during the palate shelves fusion and therefore lay a good foundation for possible therapeutic intervention and prevention of cleft palate in the high-risk group.