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.
We utilize an integrated approach in our studies, including synthesis of functional/clinical genomics, clinical tumor specimen interrogation, meso-scale/clinical imaging, transgenic murine/induced pluripotent cell models, and 3D-printing methods. Our work demonstrating essential contribution of dopamine neuro-transmission to brain tumor mitogenesis has led to an ongoing clinical trial at the University of Minnesota investigating the anti-neoplastic effects of dopamine receptor 2 (DRD2) inhibition in glioblastomas, the most common form of brain cancer in adult. Our finding that microglia, though exerting anti-tumoral effects in its native state, is reprogrammed by cancer cells to facilitate glioblastoma growth, has led to the development of a new class of clinical therapeutics. In collaboration with Timothy Ebner, another faculty in the Graduate Program in Neuroscience, meso-scale imaging unveiled the impacts of tumor growth on the neural connectome, availing opportunities for early detection diagnostics. These and other ongoing work in our group aim to improve our understanding of CNS physiology as well as clinical outcomes for patients afflicted with brain cancer.