Here in the Steele Lab, our current projects relate to the understanding of the pulmonary immune responses, both acute and chronic, to the opportunistic fungal pathogen Aspergillus fumigatus. Our acute model mimics the pathology observed in invasive pulmonary aspergillosis and our major focus is on the cytokine IL-22. Specifically, we investigate pathways that positively and negatively regulate IL-22 production as well as the antifungal immune pathways induced by IL-22. Themes in this area of investigation include common γ-chain cytokines, innate lymphocytes, and eicosanoid biology.
An important shift in the lab over the last several years has been an emphasis on the identification of inflammatory biomarkers, immune cells and pathways in human lung diseases that correlate with functional decline, and bringing these observations back to experimental animal models to provide mechanistic insight (i.e. bedside-to-bench). To this end, during chronic exposure, which is a model of severe asthma with fungal sensitization as well as chronic fungal exposure during diseases such as cystic fibrosis, our major focus is on various inflammatory mediators we have identified in human subjects. Themes in this area of investigation include various IL-1 family members, unique chemokines and chitinases/chitinase-like proteins.
Recent Publications
Hematopoietic 12/15-lipoxygenase activity negatively contributes to fungal-associated allergic asthma Makullah, M., D. Ellis, M. Jones and C. Steele. American Journal of Physiology Lung Cellular and Molecular Physiology 325:L104-L113 (2023).
Protein-protein interactive networks identified in bronchoalveolar lavage fluid of severe asthma
Protein-protein interactive networks identified in bronchoalveolar lavage fluid of severe asthma. Hastie, A.T., A.C. Bishop, M.S. Khan, E.R. Bleecker, M. Castro, L.C. Denlinger, S.C. Erzurum, J.V. Fahy, E. Israel, B.D. Levy, D.T. Mauger, D.A. Meyers, W.C. Moore, V.E. Ortega, S.P. Peters, S.E. Wenzel and C. Steele. Clinical and Experimental Allergy 54(4):265-277 (2024).
Fungal chitin is not an independent mediator of allergic fungal asthma severity
Fungal chitin is not an independent mediator of allergic fungal asthma severity. Ellis D.A., M. Jones, H.M.E. Willems, S.M.Cheung, M..Makullah, V. Aimanianda and C. Steele. American Journal of Physiology Lung Cellular and Molecular Physiology 327:L293-L303 (2024).
Pseudomonas infections persisting after CFTR modulators are widespread throughout the lungs and drive lung inflammation. Durfey SL, Kapnadak SG, Pena T, Willmering MM, Godwin JD, Teresi ME, Heltshe SL, Vo AT, Villacreses RA, Aliukonyte I, Boyken L, Stroik MR, Morgan SJ, Wang GM, Betts HL, Zhang S, Goss CH, Clancy JP, Aitken ML, Steele C, Feder AF, Esther CR Jr, Tiddens HAWM, Woods JC, Stoltz DA, Singh PK. Cell Host Microbe. 2025 Aug 13;33(8):1428-1445.e4
Type 1 conventional dendritic cells regulate innate immunity during fungal pneumonia
Type 1 conventional dendritic cells regulate innate immunity during fungal pneumonia. Dhruva P.M., T.E. Draper, C.A. Chiller, M. Jones and C. Steele. mBio 2025 Sep 22:e0256425.
