Research Projects

Pancreatic ductal adenocarcinoma (PDAC) is responsible for 90% of all pancreatic cancer cases, with oncogenic KRAs mutations accounting for at least 80% of cases. The best way forward towards targeted therapy is to target a protein that can interfere with the RAs-CRAF-ERK pathway or contribute to drug resistance, such as Gemcitabine resistance. A major candidate for this direction is matricellular oncoprotein Cyr61, which has been shown to contribute significantly to PDAC development. Exosomes originating from cancer cells or cancer microenvironments also contribute significantly to tumor development. This study aims to understand the role of Cyr61 in the production of exosomes, specifically exosomes, in PC cells and whether they could modulate the process of PDAC development. The project has two objectives: to isolate and characterize pancreatic cancer cell-derived exosomes, and to investigate the role of PC-derived exosomes in Cyr61-mediated Pancreatic Cancer development. To achieve this objective, PC cell lines with elevated levels of Cyr61 and PC cells with negligible levels will be cultured, and Cyr61KO of Panc-1 and AsPC-1 cells will be generated. The isolated exosomes will be characterized by western blot and Nanoparticle Tracking, and further enriched with human recombinant Cyr61 protein to validate its effect on PDAC. The study will also evaluate the effects of exosomes on PC development using various assays, including Trans-well migration assay, soft-agar anchorage-independent growth assay, Colony formation assay, and 3D-culture sphere formation assay. EMT markers and stemness markers will be evaluated using western blot.