My laboratory is interested in the identification and characterization of protease and protease inhibitor genes involved in cancer migration, invasion and metastasis. We are also interested in the newly identified bidirectional gene pairs (whose transcriptional start sites are separated by less than 1,000 base pairs of intergenic DNA) and their implications for the pathogenesis of various disorders, including cancer. We are also heavily involved in extramural research projects by using chemical synthesis, structural bioinformatics and pharmacological approaches in an attempt to develop new cancer treatments.
RESEARCH ACTIVITIES & ACCOMPLISHMENT
Through our patented in vitro invasion assay system, we had screened and determined an array of protease/inhibitor genes that may contribute to tumor cell migration and invasion. Notably, many identified invasion-suppressing genes belong solely to the serpin superfamily of serine protease inhibitors, and that most members of the kallikrein (KLK) 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 were identified to vastly promote the invasiveness of tumor cells. Besides, recent evidences have suggested that in the human genome some protease/inhibitor genes tend to form head-to-head bidirectional gene pairs with two genes separated only by less than 1 kp. Two such pairs, known as the SERPINI1-PDCD10 and the PREPL-C2ORF34 gene pairs, were found to be evolutionarily conserved and that their expressions are tightly regulated by distinct transcription factor(s) binding to a critical bidirectional promoter within the small intergenic DNA region.