Our Laboratory studies tumor initiation in glandular tissues at the interface of tissue homeostasis and tumorigenesis. We investigate how pre-neoplastic cells remain quiescent within histologically normal tissue, and how these quiescent mutant cells evade tissue homeostatic control to initiate neoplastic outgrowth. We also investigate parallel mechanisms that underlie tumor dormancy and recurrence after cancer treatment. Our overarching goal is to develop strategies to intervene tumor development from the initial stages of tumorigenesis and to target tumor dormancy.
Tumor initiation is one of the least understood areas of cancer biology. Tumorigenesis is a clonal evolution process initiated from sporadic mutant cells that arise within normal tissues. These pre-neoplastic mutant cells can remain largely quiescent and persist within histologically normal tissue over extended period of time. Overcoming the tightly regulated tissue environment to initiate neoplastic outgrowth represents one of the critical early steps of tumor development.
The complex signaling and morphodynamic interactions between mutant and neighboring normal cells within the tissue architecture raise new cell biological questions during tumor initiation. Our laboratory utilizes three-dimensional (3D) organotypic cultures and custom-designed molecular tools to reconstruct oncogenic circuitry at single-cell resolution within the tissue context of early human tumorigenesis. We have also developed animal models to study tumor initiation in the mouse mammary gland. Our studies employ a wide range of cell and molecular biology techniques, time-lapse 3D live-cell imaging, high-content 3D screening assays, and genomic and proteomic approaches to elucidate the mechanisms that underlie tumor initiation, tumor dormancy and recurrence.