Research Interests
Allergic asthma is the fastest growing childhood illness in the United States, affecting nearly 10% of American children and burdening the healthcare system >$50 billion per year. A major impediment to reversing this disturbing trend is an incomplete understanding of the basic mechanisms underlying allergic asthma.
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The Wiesner lab investigates two aspects of allergic asthma: sensitization and persistence. The first project (sensitization) centers on the earliest response to allergen exposure, whereby lung epithelial cells respond to cell junction damage caused by inhalation of fungal protease allergens. We explore mechanotransduction, calcium amplification circuits, and calcineurin-dependent transcription factors that form a complete signaling pathway within epithelial cells that lead to the priming of maladaptive immunity. The second project (persistence) focuses on allergen-specific, memory T cell residence in the lungs. Our lab has developed a model system and reagents that allow us to study long term maintenance of CD4+ T cells in the lungs of allergen sensitized mice. This project partly aims to apply practical approaches to directly delete allergen-specific memory T cells, and the other part aims to understand the signals exchanged between T cells and the stromal tissues that supports memory T cell residence in the lungs.
Publications
Brennan PJ, Caballes NWS, Mercado-Feliciano A, Wu YF, Wiesner DL. Efficient Method for Imaging Murine Lungs that Preserves Spatial Dynamics of Fungal Spores in the Airway. JoVE (2024). In press.
Shapiro A, Caballes NWS, Vera RN, Klein BS, Brennan PJ, Wu Y, and Wiesner DL. “Sensitization with fungal protease allergen establishes long-lived, allergenic helper T cell memory in the lung”. J Immunol (2024) 212 (9): 1420–1427.
Wiesner DL, Merkhofer RM, Ober C, Kujoth GC, Niu M, Keller NP, Gern JE, Brockman-Schneider RA, Evans MD, Jackson DJ, Warner T, Jarjour NN, Esnault SJ, Feldman MB, Freeman M, Mou H, Vyas J, and Klein BS. “Club cell TRPV4 serves as a damage sensor driving lung allergic inflammation.” Cell Host & Microbe. 2020 Apr 8;27(4):614- 628.e6.
Sui P, Wiesner DL, Xu J, Yu C, Deutsch G, Lee J, Locksley R, Klein BS, Sun X. "Pulmonary Neuroendocrine Cells are Essential for Allergic Asthma Responses." Science. 2018 Jun 8;360(6393).
Henandez-Santos N, Wiesner DL, Fites FS, McDermott A, Warner T, Wüthrich M, Klein BS. "Lung Epithelial Cell Regulation of Innate Antifungal Immunity." Cell Host & Microbe. 2018 Apr 11:23(4):511-522.
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Wiesner DL, Klein BS. "Lung Epithelium: Barrier Immunity to Inhaled Fungi and Driver of Fungal-associated Allergic Asthma." Current Opinion in Microbiology. 2017 Dec 40:8-13.