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 sixth year at the NIEHS since inception. We have now published several manuscripts. Publications since the last annual report: 1) an report using proteomic analysis to profile the complement of acylated (fatty acid-modified) proteins in the macrophage, and then validating the role of acylation in function of one such protein, phospholipid scramblase 3 (Merrick BA et al., Mol Cell Proteomics 2011) 2) a collaborative publication reporting the human Toll like Receptors are target genes of the master transcription factor p53 (Menendez D et al., PLoS Genetics 2011). 3) a collaborative publication describing the role of the cholesterol transporter ATP Binding Cassette transporter A1 in control of inflammatory signaling by macrophages (Zhu X et al., J Lipid Research 2010). 4) a review article describing how the flow of lipids through the plasma membrane of macrophages controls their inflammatory signaling (Fessler MB and Parks JS, J Immunology 2011). Additional accomplishments since our last report include an invitated talk delivered by Dr. Fessler at the 2011 Gordon Research Conference on Atherosclerosis and at the Duke University Airway Biology Forum, as well as an invitation to speak at the Fall 2011 Pulmonary Research Group Symposium (Stowe, VT). Dr. Fessler also had notable roles at the 2011 American Thoracic International Conference, including organizing/chairing and speaking at a scientific symposium, chairing a poster discussion session, and acting as facilitator at two additional thematic poster sessions. In addition, Dr. Saiful Chowdhury, a postdoctoral fellow in Fessler laboatory, received a 2011 NIH Fellows Award for Research Excellence. Dr. Fessler and his fellow, Dr. Jim Aloor, also established a provisional patent application on 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
6
Fiscal Year
2011
Total Cost
$1,748,422
Indirect Cost
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State
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Kamal, Abu Hena M; Fessler, Michael B; Chowdhury, Saiful M (2018) Comparative and network-based proteomic analysis of low dose ethanol- and lipopolysaccharide-induced macrophages. PLoS One 13:e0193104
Fessler, Michael B (2018) The challenges and promise of targeting the Liver X Receptors for treatment of inflammatory disease. Pharmacol Ther 181:1-12
Kumar, Ashutosh; Triquigneaux, Mathilde; Madenspacher, Jennifer et al. (2018) Sulfite-induced protein radical formation in LPS aerosol-challenged mice: Implications for sulfite sensitivity in human lung disease. Redox Biol 15:327-334
Fessler, Michael B (2017) A New Frontier in Immunometabolism. Cholesterol in Lung Health and Disease. Ann Am Thorac Soc 14:S399-S405
Fessler, Michael B (2017) CO2 as a Potential Obesogen: A Gas That Will Stick to Your Ribs. Am J Respir Cell Mol Biol 57:499-500
Sakamachi, Yosuke; Morioka, Sho; Mihaly, September R et al. (2017) TAK1 regulates resident macrophages by protecting lysosomal integrity. Cell Death Dis 8:e2598
Suratt, Benjamin T; Ubags, Niki D J; Rastogi, Deepa et al. (2017) An Official American Thoracic Society Workshop Report: Obesity and Metabolism. An Emerging Frontier in Lung Health and Disease. Ann Am Thorac Soc 14:1050-1059
Henderson, Michael W; Madenspacher, Jennifer H; Whitehead, Gregory S et al. (2017) Effects of Orally Ingested Arsenic on Respiratory Epithelial Permeability to Bacteria and Small Molecules in Mice. Environ Health Perspect 125:097024
Azzam, Kathleen M; Madenspacher, Jennifer H; Cain, Derek W et al. (2017) Irgm1 coordinately regulates autoimmunity and host defense at select mucosal surfaces. JCI Insight 2:
Gabor, Kristin A; Fessler, Michael B (2017) Roles of the Mevalonate Pathway and Cholesterol Trafficking in Pulmonary Host Defense. Curr Mol Pharmacol 10:27-45

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