The goal of my laboratory is to understand the molecular rewiring that occurs in cancer in order to deepen our fundamental understanding of this disease and potentially identify new therapeutic opportunities. We use functional genomics applied to mouse and human systems to understand the transcriptional networks that regulate the outcome of specific oncogenic mutations. We have two primary disease interests: lung cancer and pediatric sarcomas. We have used functional genomics in mouse and human models to identify novel synthetic vulnerabilities for oncogenic KRAS (Vicent et al, 2010, JCI and Gwinn et al 2018, Cancer CelI) and identified and characterized the role of tumor-propagating cells and the importance of the Notch pathway in lung cancer (Zheng et al, 2013, Cancer Cell). Most recently, we have described a potential new therapeutic approach for lung cancer involving targeting of a cytokine produced by cancer associated fibroblasts (Marquez et al, Nature Medicine, in press). In our sarcoma work, we are interested in mechanisms driving osteosarcoma and Ewing sarcoma progression and therapy resistance (Howarth et al, JCI, 2014, Sayles and Breese, Cancer Discovery, 2019). We rely on computational genomic analysis and we have extensive experience in generating next-generation sequencing datasets for gene and network discovery using both primary tumors and human and mouse model systems.