Pancreatic cancer is a devastating malignant disease that is difficult to diagnose early and is refractory to most therapies. There are urgent needs to identify new therapeutic strategies and diagnostic biomarkers for pancreatic cancer. A hallmark feature of pancreatic cancer is its desmoplastic ‘scar-like’ stroma, highly enriched in type I collagen. The immunosuppressive ecosystem is another hallmark feature of PDAC that emerges as the key obstacle to immunotherapy response. Our prior studies established multiple transgenic mouse models with the genetic deletion of type I collagen in various cell lineages and discovered the distinct roles of type I collagen in pancreatic cancer. These studies identified the functional heterogeneity of tumor stromal components (such as type I collagen) and cell populations (such as cancer-associated fibroblasts, cancer cells, and immune cells). In addition, these studies underscored the interactions between tumor stromal components, tumor immune response, and intratumoral microbiome profile.
The Chen Laboratory is focusing on understanding the key mechanism
that controls the two hallmark features of pancreatic cancer: the desmoplastic
stroma and the immunosuppressive microenvironment. We integrate computational biology (utilizing single-cell sequencing, spatial transcriptomics, and other multi-omics analyses) with experimental biology (utilizing sophisticated transgenic mouse models), in conjunction with the analysis of cancer patient datasets. Such multi-disciplinary research system will allow the systemic identification and investigation of novel therapeutic targets and diagnostic biomarkers in pancreatic cancer and other diseases.