Mentoring patient-oriented researchers in inflammatory airway disease

Abstract The overall goal of the proposed research is to identify novel aspects of human innate lymphoid cell (ILC) biology in airway diseases using patient-oriented research (POR) and through mentoring junior clinical investigators. The candidate has a strong record of mentoring individuals at many levels including clinical investigators in multiple specialties. The mentoring plan includes recruitment and training of fellow and faculty investigators from three disciplines (allergy, otolaryngology, and pulmonary) within the UCSD Center for Asthma and Sinus Disease center of excellence to foster the careers of junior investigators and perform outstanding POR. There are currently large gaps in our understanding of the roles of ILCs in human sinus disease and asthma which cause significant morbidity worldwide. ILCs are divided by the types of cytokines they secrete and ILC2s that secrete Th2 cytokines have been shown to promote airway inflammation in animal models. Importantly, recent work has shown that ILC2s are increased in samples from patients with asthma and chronic rhinosinusitis (CRS). Our group was the first to show that ILC2s are increased in a subgroup of nasal polyps in CRS that contain eosinophils and are also recruited to the nose after aspirin challenge in patients with aspirin-exacerbated respiratory disease (AERD). AERD patients have severe sinus disease with nasal polyps, moderate to severe asthma, and respiratory reactions to aspirin and similar compounds. In the current proposal, we will test the hypothesis that through the use of cutting-edge technology (single cell RNA-seq) we will be able to identify specific subgroups or “endotypes” of patients with CRS and asthma by tissue and blood ILC subset composition. We also posit that biologic blockade of type 2 inflammation in AERD, asthma and CRS patients will reduce ILC2 recruitment to the airway. Critically, this award will provide protected time for POR in sinus disease and asthma and allow for outstanding mentorship of the next generations of POR investigators.