Insertional mutagenesis to identify molecular mechanisms of breast cancer dormancy and metastasis
Metastatic disease is the leading cause of cancer deaths, yet our understanding of this process and therapeutic choices are extremely limited. The recent explosive development of high-throughput technologies in genomics and proteomics has begun to unravel the complexity of cancer biology, highlighting the need to approach the study of cancer from a systems biology perspective. Results of recent studies have underscored the crucial roles of the tumor microenvironment as well as cell-intrinsic processes, such as autophagy, in cancer cell survival and dissemination. These surviving cells may lay dormant or be triggered to proliferate and establish active metastatic lesions after a variable period of time. I propose an innovative project in which I will exploit the unique opportunity to dissect molecular mechanisms controlling breast cancer dormancy and metastasis employing cutting-edge technologies in the field of functional genomics. This technology includes several state-of-the-art technical advances in the fields of in vitro and in vivo modeling of tumor cell dormancy, functional forward genomics using the PiggyBac transposon-based system for insertional mutagenesis screens, next generation sequencing, advanced bioinformatics and in vitro and in vivo functional validation studies. This project will identify critical molecular processes involved in breast cancer progression and potential therapeutic targets against breast cancers at high risk for recurrence and poor prognosis. Thus, it is expected that this project will provide future translational research avenues, enhance my position to be at the forefront of cancer research and provide the opportunity to establish myself as an independent researcher following the completion of this fellowship.