The Host Defense Group of the Laboratory of Respiratory Biology, Division of Intramural Research, National Institute of Environmental Health Sciences, headed by Michael B. Fessler, MD now enters its seventh year at the NIEHS since inception. We have now published several manuscripts. Publications since the last annual report include: 1) a report identifying a novel role for the cholesterol transporter ABCG1 in adaptive immune responses in the lung (Draper D et al., J Immunology 2012) 2) a collaborative publication reporting that obesity leads to abnormalities in innate immune responses in the mouse lung (Kordonowy et al., Am J Respir Cell Mol Biol 2012) 3) a collaborative publication describing a novel role for signaling lipids that derive from CGI-58 in inflammation and in insulin action (Lord CC et al, Diabetes 2012). 4) 2 review articles describing effects of cholesterol on inflammation in the lung and on innate immune responses by leukocytes (Gowdy K et al, Pulm Pharmacol Ther 2012;Azzam K et al., Trends Endocrinol Metab 2012). 5) an invited editorial commenting on a publication that describes effects of cholesterol efflux on mobilization of stem cells from the bone marrow (Suratt BT et al., Cell Stem Cell 2012) 6) a report (in press) describing a novel relationship between serum allergen-specific immunoglobulin E (a measure of atopy) and myocardial infarction in the U.S. population (Jaramillo et al., J Allergy Clin Immunol 2012) Additional accomplishments since our last report include invited talks by Dr. Fessler at Ohio State University, Johns Hopkins University, University of Missouri Kansas City, East Carolina University, and NIH Clinical Center Grand Rounds. Dr. Fessler also served as a poster session facilitator at the 2012 American Thoracic Society International Conference, received an career development award (Carol Basbaum Award) from the American Thoracic Society, and was also invited to serve as a reviewer on an ATS study section. In addition, Dr. Saiful Chowdhury, a postdoctoral fellow in Fessler laboatory, recently left Fessler laboratory to start a new faculty job as Assistant Professor in the Dept. of Chemistry and Biochemistry, University of Texas at Arlington. Dr. Fessler and his fellow, Dr. Jim Aloor, also completed filing of a pending patent that describes a novel protein that shows potential as a regulator of inflammatory responses (Provisional Patent Application #61/443,491: Modulation of Lrch4 activity and Therapeutic Application Thereof (filed January 17, 2011;inventors: Michael B. Fessler, Jim J. Aloor)).

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2012
Total Cost
$1,867,515
Indirect Cost
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State
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Shaikh, Saame Raza; Fessler, Michael B; Gowdy, Kymberly M (2016) Role for phospholipid acyl chains and cholesterol in pulmonary infections and inflammation. J Leukoc Biol 100:985-997
Lai, Lihua; Azzam, Kathleen M; Lin, Wan-Chi et al. (2016) MicroRNA-33 Regulates the Innate Immune Response via ATP Binding Cassette Transporter-mediated Remodeling of Membrane Microdomains. J Biol Chem 291:19651-60
Fessler, Michael B; Summer, Ross S (2016) Surfactant Lipids at the Host-Environment Interface. Metabolic Sensors, Suppressors, and Effectors of Inflammatory Lung Disease. Am J Respir Cell Mol Biol 54:624-35
Barna, Barbara P; McPeek, Matthew; Malur, Anagha et al. (2016) Elevated MicroRNA-33 in Sarcoidosis and a Carbon Nanotube Model of Chronic Granulomatous Disease. Am J Respir Cell Mol Biol 54:865-71
Gabor, Kristin A; Fessler, Michael B (2016) Roles of the Mevalonate Pathway and Cholesterol Trafficking in Pulmonary Host Defense. Curr Mol Pharmacol :
Fessler, Michael B (2015) Revisiting "Good" and "Bad" Cholesterol. The Battle over Flow through Arteries Now Shifts to Flow through Airways. Am J Respir Crit Care Med 191:969-70
Gowdy, K M; Madenspacher, J H; Azzam, K M et al. (2015) Key role for scavenger receptor B-I in the integrative physiology of host defense during bacterial pneumonia. Mucosal Immunol 8:559-71
Romero, Freddy; Shah, Dilip; Duong, Michelle et al. (2015) A pneumocyte-macrophage paracrine lipid axis drives the lung toward fibrosis. Am J Respir Cell Mol Biol 53:74-86
Gordon, Scott M; McKenzie, Benjamin; Kemeh, Georgina et al. (2015) Rosuvastatin Alters the Proteome of High Density Lipoproteins: Generation of alpha-1-antitrypsin Enriched Particles with Anti-inflammatory Properties. Mol Cell Proteomics 14:3247-57
Fessler, Michael B (2015) Regulation of Adaptive Immunity in Health and Disease by Cholesterol Metabolism. Curr Allergy Asthma Rep 15:48

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