Our research program is focused on understanding the reciprocal interactions between brain cancer cells and the unique microenvironment of the central nervous system (CNS). Elements of the CNS microenvironment fundamentally differ from those of other anatomic compartments, characterized by microglia immune surveillance, high density of synaptic transmission, and an unique extracellular matrix. Dynamic interplays between these constituents and the cancer cell modulate all aspects of tumor biology, including DNA damage response, immune invasion, metabolic energetics, and cancer stem cell states. Moreover, cancer cells interface with neural elements to influence intrinsic physiology and neuro-network. From a basic science perspective, studies of this dynamic interplay offer a glimpse into the biologic processes that govern the inner workings of the CNS. Clinically, these interplays dictate clinical survival and quality of life for patients afflicted with brain cancer; insights into these reciprocal communications afford opportunities for diagnostic and therapeutic development.