PROJECT SUMMARY Chronic rhinosinusitis (CRS) is a common inflammatory disease that affects a large portion of the U.S. population, resulting in poor quality of life for those affected and utilizing billions of dollars of health care resources. Efforts in my lab have focused on understanding patterns of inflammatory heterogeneity in large CRS populations with a goal of improving disease endotyping and developing personalized care pathways. I am devoted to mentoring the next generation of clinician-scientists in the field of rhinology and chronic rhinosinusitis research. The number of physicians and other surgeons pursuing clinical or translational research is declining, and this is particularly true in the fields of rhinology and otolaryngology. Maintaining a strong pipeline of trainees on research-related career paths is crucial for the development of the subspecialty and scientific advancement of the field. This will be a prospective translational cohort study to identify the clinical implications and longitudinal stability of chronic rhinosinusitis endotypes. We will enroll CRS patients through our well-established biospecimen repository and determine the stability of inflammatory mediator levels and associated endotype assignment over multiple seasons and determine whether these changes are associated with sinonasal microbial community structure. We will also confirm the longitudinal effects of two commonly used immune-modifying interventions (endoscopic sinus surgery and anti-IL4/13R biologic therapy) on inflammatory mediator levels and endotypic assignment. Collectively, these translational studies will substantially advance basic knowledge of a common airway disease that impacts millions of patients, while providing a range of investigative opportunities for mentees interested in CRS and mechanisms of upper airway inflammation. My research program is centered around a patient-oriented approach that incorporates patient-derived specimens, patient-reported outcome measures, and personalized approaches to care. I anticipate that mentee participation in this research program will lead to new and exciting avenues for patient-oriented research to further characterize CRS endotypes and evaluate the effects of targeted therapies; thus, this project will provide a conducive setting for developing the next generation of clinician-scientists in the field. I have a history of continual extramural funding, more than a decade of experience as a mentor to trainees at all levels, and institutional support to enhance my own skills that will augment the support proposed through the K24 mechanism.