Our understanding of cancer has been challenged in nearly every regard. “Potent” oncogenic mutations are insufficient to drive tumorigenesis from most cells. What, then, enables cancer initiation? Do rare tumor-initiating cells have a unique permissive epigenetic state or happen to receive signals from a supportive local microenvironment? Additionally, tumor cells spread through the body early in disease, often as cluster of heterogeneous mesenchymal-like and epithelial-like cells. The vast majority of disseminated cells will die, and only a select few drive metastatic outgrowth. What properties endow those rare cells to initiate metastases?

 

Our lab focuses on addressing these long-standing questions by investigating how tissue injury and tumor-microenvironment interactions contribute to disease progression in pancreatic and breast cancer. We study patients in which cancer progression is either diminished or enhanced as a platform for determining anti- or pro-tumorigenic signals, respectively. We employ multiplexed single cell analyses of tumor and microenvironmental cell populations to identify signals that contribute to metastasis or therapy resistance. Further, we utilize mouse models that enable tracking of cell-cell interactions and tumor cell states through time. Finally, we focus on functionally testing targets that may be therapeutically actionable with the goal of moving our findings into the clinic to improve patient outcomes.