The Knox Lab research program investigates the role of peripheral nerves in controlling epithelial organ development, regeneration, and chronic disease (autoimmune disease, aging, cancer). To explore these areas, we utilize a multiorgan approach that includes the salivary glands and cornea. Our experimental approach employs a bevy of tools that define cell identity, cell-cell relationships and cell/tissue behavior during development and response to injury and regenerative cues including mouse genetics, single cell/bulk RNA sequencing, organoids, atomic force microscopy, ex vivo organ culture, hydrogel synthesis (mechanical, physical and biological testing etc.) and high-resolution imaging. Using this strategy, we have discovered essential functions of peripheral nerves in regulating stem cell maintenance, differentiation and maturation, tissue morphogenesis and regeneration, and cell lineage outcomes. We have also uncovered multiple aspects of nerve-epithelial cell interactions and factors that drive reinnervation. Importantly, our basic research has led to the initiation of translational projects. For example, based on our recent discovery of a nerve-derived factor that promotes glandular repair after radiation-induced damage, we designed a drug-hydrogel system that provides local penetration of irradiated tissue for achieving long-term functional and structural regeneration. This therapeutic product has the potential to regenerate the salivary glands of patients who have received radiotherapy for head and neck cancer, an off target injury for which there are no regenerative therapies, and poor palliative therapies. These studies are funded by the CDOCTOR/NIDCR program and the California Institute for Regenerative Medicine translational award (TRAN1). We have conducted a pre-IND and are currently performing a pre-clinical trial in 2 large animal models (dog and rabbit) to meet the needs of the FDA for clinical translation.