The primary reason people die from cancer is the development of metastatic disease. As a surgeon-scientist who cares for patients with earlier stage lung and esophageal cancer, my laboratory studies why patients with completely resected cancer still develop metastases and die. We focus on a class of genes known as metastasis suppressor genes and, in particular, breast cancer metastasis suppressor I (BRMS1). We have identified important functions of BRMS1 as a transcriptional repressor, an E3 ligase, and a mediator of RelA/p65 transcription in lung cancer. We investigate BRMS1-mediated suppression of metastases in p53mut lung adenocarcinoma (LUAD), as well as the identification of a novel germline point mutation of BRMS1 variant 2, a pro-metastatic variant. Currently, we are exploring the role of the tumor immune microenvironment in BRMS1-loss tumors. Our lab is also examining tumor genomics in early stage LUAD and has built a comprehensive clinically- and genomically-annotated database. Our recent focus is LUAD organotropism, or the preferential metastasis to specific organ sites, and we have identified specific mutations that drive site-specific metastasis of LUAD. Over the past several years, we have established a large patient-derived organoid (PDO) program to explore the biology of metastases and related therapies in vitro and in novel mouse models of metastases. Finally, we have initiated a prospective study examining the role of tumor-related exosomes and extravesical particles in the development of metastases in operable lung cancer patients. Collectively, the goal of my laboratory is to understand the biology of metastases in early-stage lung and esophageal cancer and develop therapies to mitigate this deadly process.