The Tsao Laboratory is focused on translational research projects in lung and pancreatic cancer at the Princess Margaret Cancer Centre/Ontario Cancer Institute, the largest cancer research and treatment facility in Canada and one of the top 5 cancer research centres in the World.

The primary goals of our lung cancer projects are to identify novel genes or proteins that are better than clinical predictors alone in predicting clinical outcome or response to therapies. We profile the gene expression and genomic aberrations of a large number of human lung cancer samples using microarray techniques, apply computational bioinformatic algorithms to identify the predictive genes or gene signatures, and validate them by realtime quantitative PCR techniques. The biological functions of the predictive genes are then studied using in vitro lung cancer cell line models, organoid models, primary lung cancer xenograft models and orthotopic rodent models of human lung cancers. Conversely, high-throughput drug screening in PDX, organoids and PDX-derived cell lines are used to identify therapeutic targets. We then survey genomic and transcriptomic profiles of these models via exome seq, CNV and gene expression profiling to identify target aberrations and correlate them with drug response.

The primary goal of our pancreatic cancer project is to dissect the molecular basis of human pancreatic cancer, which mostly arises from the duct epithelium. Our laboratory was the first to establish primary cultures of normal human pancreatic duct cells. Immortalized cell lines derived from these primary cultures are used to study the activities of oncogenes and tumor suppressors that are commonly aberrant in pancreatic cancer. The approach provides insights into key molecular events that may be targeted to prevent and treat pancreatic cancer. Special interest and emphasis involve the signaling of epidermal growth factor receptor (EGFR), Met/hepatocyte growth factor receptor and KRAS. These two growth factor signaling loops play important roles in the growth and metastasis of lung, pancreatic and colorectal cancer. We are also investigating the role of mutations and overexpression of these genes in the biology of these cancers.