By understanding the mechanisms that regulate thymus atrophy, we can design rational strategies to delay or reverse loss of thymus function during aging. The thymus retains a remarkable capacity to regenerate, even very late in life, but known approaches for regeneration are transient, and durable regeneration has not been achieved. Ongoing projects aim to apply what we’re learning to durably improve T cell responsiveness to pathogens and tolerance to self in aging. For instance, recent work has suggested that paracrine FGF21 signaling between thymic epithelial cells regulates the extension of cellular processes that are characteristic of the unique labyrinth-like morphology exhibited by cortical thymus epithelial cells (cTECs). This labyrinth type cTEC morphology is critical for maintaining thymus size in young animals, and for regrowth of the thymus during experimental regeneration. We aim to characterize the signaling pathways that regulate cTEC morphology to identify novel therapeutic targets for boosting thymus function. Sarah and Aaron are both working on new mTEC-specific knock-in mouse models to explore paracrine epithelial cell signaling in the thymus, and Kahealani is investigating the impact of thymus regeneration on T cell responses to influenza vaccination and infection.

Papers: Venables 2019 (Petrie lab), Hester 2022

Current funding: R21AG081709, R21AI166843, R21AI154109

Past funding: R56AI153626