Angiosarcoma is a rare type of soft tissue sarcoma, with a prevalence of fewer than 300cases in the US annually. Our understanding of the oncogenic mechanisms of aggressive angiosarcomas is rudimentary, and our ultimate goal is to develop appropriate and effective treatment options and protocols for patients with this disease. Angiosarcoma are genomically complex; however, they share a histological morphology that consists of disorganized, malignant vessel-forming cells. Our hypothesis is that chromatin accessibility is necessary to establish the mutational landscape, which consequently activates convergent signaling pathways that contribute to angiosarcoma development. We will establish chromatin accessibility and the transcriptomic landscape in angiosarcomas, develop in vitro tumor models to define molecular mechanisms that regulate convergent oncogenic pathways in angiosarcomas, and to determine if p53 deficiency in hemangioblasts contributes to angiosarcoma development. This project will impact our understanding of aggressive angiosarcomas and specifically enhance our basic knowledge of how morphologic convergence with genetic chaos arises and contributes to angiosarcoma development. This career development award also supports the PI, Dr. Kims career goal to develop an independent, extramurally funded research program to advance our understanding of aggressive sarcomas.