The O’Donnell laboratory is focused on understanding the mechanisms that contribute to tumor initiation, progression, and metastasis. Our laboratory has made significant contributions to the development and utilization of ex vivo and in vivo transposon mutagenesis systems for the discovery of new cancer genes. Using these systems, we have identified novel genes that promote liver cancer, leukemia, and non-small cell lung cancer. These approaches enabled our discovery of oncogenic cell surface receptors in lung cancer, which we are currently investigating using molecular and biochemical studies, and mouse models. These studies may provide new therapeutic approaches to target cancer cells.