Theodore J. Standiford, M.D.
Professor, Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine

tstandif@umich.edu

The central thrust of the studies performed in Dr. Standiford's laboratory has focused on exploring the role of toll like receptors (TLRs) to the generation of inflammatory cytokines/chemokines required for protective innate immune responses of the lung. Murine models of bacterial and fungal pneumonia have been developed to determine the contribution of TLRs/cytokines to the generation of effective pulmonary innate immunity. Specific pulmonary pathogens being studied include Klebsiella pneumoniae , Pseudomonas aeruginosa , Legionella pneumophila , and Aspergillus fumigatus . Gene therapy and gene deletion/transgenic techniques have been applied to identify relevant mediators and novel therapeutic approaches. Studies are ongoing to determine the contribution of dendritic cells and specific T cell populations as important links between innate and acquired immune responses within the lung. Additional studies are ongoing to define the role of inhibitors of TLR signaling cascades to sepsis-induced macrophage deactivation. Finally, the identification of host-derived factors that control the magnitude of inflammatory responses in the setting of sepsis-induced acute lung injury is an active area of investigation.

Representative Publications

Tateda K, Deng JC, Moore TA, Newstead MW, Paine R III, Kobayashi N, Yamaguchi K, Standiford TJ. Hyperoxia mediates acute lung injury and increased lethality in murine Legionella pneumonia: The role of apoptosis. J Immunol 170:4209-16, 2003.

Deng JC, Zeng X, Newstead M, Moore TA, Tsai WC, Thannickal VJ, Standiford TJ. STAT4 is a critical mediator of early innate immune responses against pulmonary Klebsiella infection. J Immunol 173:4075-83, 2004.

Deng JC, Moore TA, Newstead MW, Zeng X, Standiford TJ. CpG oligodeoxynucleotides stimulate protective innate immunity against pulmonary Klebsiella infection. J Immunol 173:5148-55, 2004.

Zeng X, Moore TA, Newstead MW, Deng JC, Kunkel SL, Luster AD, Standiford TJ. IP-10, but not MIG, promotes protective Type 1 immunity in murine Klebsiella Pneumonia. Infect Immun 73:8226-36, 2005.

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.

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 , Cutting Edge Section (in press).