We are exposed to a constant flux of external biochemical and physical stimuli as we age. Despite variability in our overall experiences and exact constitutions, our individual tissues typically manage to maintain functionality, though each can differ in its resilience to distinct stressors.
We have characterized how differences in cellular composition and communication impact tissue fitness and have identified responses and subsequent adaptations that drive chronic dysfunction. For example, although aberrant immune activity can precipitate allergic inflammatory diseases, therapies targeting immune cells and signaling are only successful in some, suggesting chronicity may involve alternative mechanisms. Previously, we helped demonstrate that dysregulated type-2 immune signaling, driven by environmental allergens, can impact tissue health in the upper airway through generating dysfunctional basal epithelial stem cells. These stem cells can then contribute to persistence by serving as repositories for allergic inflammatory memories, altering the integrity and functional output of the nasal epithelium. Our work, with that of others, suggests generalizable principles for cellular memory, and informs where and how tissues should be targeted to support health or restore function. We have since further investigated how tissue-resident cellular subsets participate in, and are shaped by, environmental exposures at barrier tissues and the functional consequences of these experiences.
We are now working to develop a more holistic appreciation for how different intra- and extracellular factors (e.g., genetics and integrated exposure history, respectively) influence barrier tissue function.