Theodore J. Standiford,
Professor and Interim Chief, Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
The central thrust of studies performed in Dr. Standiford’s laboratory have focused on exploring the role of specific cells, cytokines, antimicrobial peptides and toll like receptors (TLRs) in the generation of protective innate immune responses of the lung. Murine models of bacterial and viral pneumonia have been developed to determine the contribution of TLRs, cells, cytokines, and antimicrobial peptides to the generation of effective pulmonary innate immunity. Gene deletion/transgenic techniques, passive immunization, and gene knockdown approaches have been applied to identify relevant mediators and novel therapeutic approaches. Additional studies are in progress to determine the contribution of dendritic cells and specific T cell populations as important links between innate and acquired immune responses within the lung. Studies are ongoing to define the effects of viral infection or systemic sepsis on subsequent lung innate antibacterial immune responses, and determine the contribution of inhibitors of TLR signaling cascades to regulation of innate responses. The epigenetic regulation of innate macrophage responses in sepsis and acute lung injury is a focus of both animal and human based translational research.
Stringer KA, Serkova NJ, Karnovsky A, Guire K, Paine R 3rd, Standiford TJ. Metabolic consequences of sepsis-induced acute lung injury revealed by plasma 1H-nuclear magnetic resonance quantitative metabolomics and computational analysis. Am J Physiol Lung Cell Mol Physiol 300:L4-L11, 2011. PMID: 20726789.
Lyn-Kew K, Rich E, Zeng X, Wen H, Kunkel SL, Newstead MW, Bhan U, Standiford TJ. IRAK-M Regulates chromatin remodeling in lung macrophages during experimental sepsis. PLoS One 5: e11145, 2010. PMC2886833
Yu F, Cornicelli MD, Kovach MA, Newstead MW, Zeng X, Kumar A, Gao N, Yoon S, Gallo RL, Standiford TJ. Flagellin stimulates protective lung mucosal immunity: role of cathelicidin related antimicrobial peptide. J. Immunol 185:1142-1149, 2010 PMID: 20566829.
Bhan U, Ballinger MN, Zeng X, Newstead MJ, Cornicelli MD, Standiford TJ. Cooperative interactions between TLR4 and TLR9 regulate interleukin 23 and 17 production in a murine model of gram negative bacterial pneumonia. PLoS One 5:e9896, 2010. PMCID: PMC2845620
Bhan U, Lukacs NW, Osterholzer JJ, Newstead MW, Zeng X, Moore TA, McMillan TR, Krieg AM, Akira S, Standiford, TJ. TLR9 is required for protective innate immunity in gram-negative bacterial pneumonia: role of dendritic cells. J Immunol 179:3937-46, 2007.
Deng JC, Cheng G, Newstead MW, Zeng X, Kobayashi K, Flavell R, Standiford TJ. Sepsis-induced suppression of lung innate immunity is mediated by IRAK-M. J Clin Invest 116:2532-42, 2006.