The accumulation of genetic and epigenetic alterations transforms normal cells into cancer cells characterized by uncontrolled proliferation. But how does cancer initiate and progress? In the hierarchy from stem cells to terminally differentiated cells, what cell types have the potential to act as target cells for cancer? And how do mutant cells gain the ability to propagate tumors in the long term? At the molecular levels, can we identify and validate novel candidate targets to inhibit cancer development? To address these questions, we study the mechanisms of central cancer pathways, including the RB pathway, during the tumorigenic process. We also investigate how cancer cells functionally interact with other cells in the tumor microenvironment, including immune cells. A focus of our group is on neuroendocrine tumors such as small-cell lung cancer. We leverage publicly-available cancer genomics data and generate our own set of genetic, epigenetic, and proteomic data sets to identify novel regulators of cancer growth. We also develop novel genetic approaches in mice to conclusively determine the function of these candidate genes and pathways in tumorigenesis in vivo. Finally, we team up with pharmaceutical companies and clinicians in academic centers to translate our discoveries into the clinic as rapidly as possible.

Keywords: RB pathway, heterogeneity, cell plasticity, stem cells, quiescence, mouse models, neuroendocrine cancer, SCLC, cell-of-origin, metastasis, functional genomics, immunotherapies