Defining the Role of Tumor-Neutral Crosstalk in head and Neck Cancer Progression and Treatment Resistance

The project will investigate the exact mechanisms driving nerves to infiltrate tumors and support their growth and progression, hypothesizing that axonal sprouting and autonomic reprogramming result from miRNA shuttling from cancer cells to neurons. It will pursue three specific aims: (1) Delineate signaling events between cancer cells and neurons during tumorigenesis using pharmacologic and genetic approaches. (2) Elucidate drivers of tumor-associated neuronal reprogramming using human-derived sensory neurons. (3) Characterize sensory nerve reprogramming and its role in oral cancer progression using a genetically engineered syngeneic mouse model. The long-term goal is to identify novel therapeutic targets by understanding reciprocal nerve-cancer signals.