Dr. Scott E. Evans
The University of Texas MD Anderson Cancer Center
Department of Pulmonary Medicine
- Lung responses to microbial infections
- Innate immune roles of epithelial cells
- Antimicrobial peptides
- Therapeutic manipulation of inflammatory responses
Infectious pneumonias result in more premature death and disability than any other condition worldwide. This problem is amplified among immunocompromised patients, such as those with hematologic malignancies or those receiving cytotoxic chemotherapy, as they are susceptible to infection by an extremely broad array of pathogens. However, even when patients receive myeloablative therapy, their lung epithelial cells remain capable of remarkable structural and functional plasticity in response to pathogen interactions. The major goal of my laboratory is to harness these lung epithelial responses to prevent the establishment of pneumonia in at risk populations.
My laboratory has found, both in vivo and in vitro, that lung epithelial cells are sufficient to kill a wide variety of respiratory pathogens. By stimulating the epithelium with combinations of pathogen-associated molecular patterns (primarily Toll-like receptor ligands), we induce intrapulmonary killing of pathogens, and demonstrate striking survival improvements despite challenges with Gram-positive, Gram-negative, viral, fungal, and even bioterror pathogens.
Graduate students in my laboratory focus on projects related to the mechanisms underlying the inducibility of microbial resistance in the lung epithelium. Projects include investigations to determine the necessary and sufficient ligand-receptor combinations for induction of resistance, dissection of the resulting signaling pathways, and the clarification of the epithelium-derived effector molecules that promote pathogen killing. These objectives are primarily investigated in vivo using knockout and transgenic mice to manipulate the genes of interest, and in vitro using epithelial cell culture techniques.
PY Hahn, SE Evans, TJ Kottom, JE Standing, RE Pagano, and AH Limper. Pneumocystis carinii cell wall β-glucan induces release of macrophage inflammatory protein-2 from alveolar epithelial cells via a lactosylceramide mediated mechanism. Journal of Biological Chemistry 2003; 278(3):2043-2050.
Evans SE, Colby TV, Ryu JH, Limper AH. Localization of transforming growth factor-β1 and extracellular matrix-associated fibronectin in pulmonary lymphangioleiomyomatosis. Chest 2004; 125(3):1063-1070.
Evans SE, Hahn PY, Lebron-Ruiz FM, Kottom TJ, Puri V, Limper AH. Pneumocystis carinii β-glucan induces chemokine production in alveolar epithelial cells by an NF-κB dependent pathway. American Journal of Respiratory Cell and Molecular Biology 2005; 32(6):490-497.
Clement CG, Evans SE, Evans CM, Hawke D, Kobayashi R, Reynolds PR, Moghaddam SJ, Scott BL, Melicoff E, Adachi R, Dickey BF, Tuvim MJ. Stimulation of lung innate immunity protects against lethal pneumococcal pneumonia in mice. American Journal of Respiratory and Critical Care Medicine. 2008;177(12):1322-30.
Tuvim MJ, Evans SE, Clement CG, Dickey BF, Gilbert BE. Augmented lung inflammation protects against influenza A pneumonia. PLoS ONE. 2009;4(1):e4176.
Safdar A, Shelborne SF, Evans SE, Dickey BF. Inhaled therapeutics for prevention and treatment of pneumonia – emphasis on the immunocompromised patient. Current Opinion in Drug Safety, 2009;8(4):435-49.
Clement CG, Tuvim MJ, Evans CM, Tuvin DM, Dickey BF, Evans SE. Allergic lung inflammation alters neither susceptibility to Streptococcus pneumoniae infection nor inducibility of innate resistance in mice. Respiratory Research 2009;10:70.
Evans SE, Scott BL, Clement CG, Pawlik J, Gilbert BE, Bowden MG, Höök M, Kontoyiannis D, Lewis RE, LaSala PR, Peterson JW, Chopra AK, Klimpel G, Tuvim MJ, Dickey BF. Stimulation of lung innate immunity protects mice broadly against bacterial, fungal and viral pneumonia. American Journal of Respiratory Cell and Molecular Biology, 2010;42:40-50.
Evans SE, Xu Y, Tuvim MJ, Dickey DF. Inducible innate resistance of lung epithelium against infection. Annual Review of Physiology, 2010;72:413-35.