Project 3: Genetic Studies in Chronic Rhinosinusitis

Genetic and environmental factors contribute to risk, but interactions between them are poorly understood. In this project, we are applying a systems genetics approach to discover genes and pathways involved in epithelial response to two important pathogens involved in chronic rhinosinusitis (CRS): human rhinovirus (HRV), which shows clinical and epidemiologic association with CRS, and Staphylococcus aureus (s. aureus), which has been implicated in CRS-related epithelial inflammation.

Functional SNPs are taken for association studies in a large cohort of ethnically diverse, well-characterized subjects with sinus disease to identify risk alleles, modifiers of disease course, and modifiers of response to environmental exposures. We employ state-of-the-art genomic and bioinformative tools and harness the benefits of the Chronic Rhinosinusitis Integrative Program (CRISP) project that include broad expertise in epidemiology, genetics, molecular and cellular biology, and clinical studies to discover and characterize the genetic architecture of CRS.

Evaluating the molecular responses to these key pathogens constitutes a major contribution toward better understanding of CRS and provides a paradigm for elucidating genetic and environmental risk factors for this disorder and other common, complex diseases of the upper airway.