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 third year at the NIEHS since inception. We have increased our staffing to 6 active laboratory members. Accomplishments include an original publication (Smoak K et al., Journal of Immunology 2008;180(5):3305-12) that defines a novel role for the nuclear receptor Liver X Receptor in modulation of pulmonary innate immunity, 3 review articles published or in press, a published and Pubmed-indexed meeting abstract on Liver X Receptor in lung inflammation (Madenspacher JH et al., Proc Am Thorac Soc. 2008 Apr;5(3):366), and an original manuscript on proteomic analysis of macrophage rafts that has been resubmitted with minor revisions (Molecular & Cellular Proteomics). Additional accomplishments include a 2009 FARE abstract award for Research Fellow Suraj Dhungana, organization and chairing by Dr. Fessler of an NIEHS Symposium on Lipid Raft Biology, hosting by Dr. Fessler of the NIEHS Distinguished Lecturer for May 2008 (Kai Simons), appointing of Dr. Fessler to the American Thoracic Society (ATS) RCMB Assembly, delivery of 5 regional research seminars by Dr. Fessler, chairing by Dr. Fessler of a genomics/proteomics poster session at the 2008 ATS International Conference, and presentation by Dr. Fessler of a poster at the Gordon Research Conference on Lipoprotein Metabolism. In addition, substantial data has been collected on 5 active research projects in the laboratory: 1) characterization of apoplipoprotein A-I as a novel stimulus of innate immunity; 2) characterization of viral fusion proteins as novel innate immune stimuli; 3) proteomic discovery of novel signaling proteins recruited to macrophage lipid rafts in response to LPS; 4) identification of a modulatory role of dyslipidemia upon pulmonary innate immunity in a murine model of inhaled LPS and in human asthma; and 5) investigation of a role for cholesterol trafficking regulators in pulmonary innate immune responses. Presently, 2 new original manuscripts are under final preparation and will be submitted imminently.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES102005-03
Application #
7734551
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2008
Total Cost
$1,920,297
Indirect Cost
City
State
Country
United States
Zip Code
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
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
Fessler, Michael B; Carnes, Megan U; Salo, Päivi M et al. (2017) House Dust Endotoxin and Peripheral Leukocyte Counts: Results from Two Large Epidemiologic Studies. Environ Health Perspect 125:057010
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:
Lowe, Julie M; Nguyen, Thuy-Ai; Grimm, Sara A et al. (2017) The novel p53 target TNFAIP8 variant 2 is increased in cancer and offsets p53-dependent tumor suppression. Cell Death Differ 24:181-191
Madenspacher, Jennifer H; Fessler, Michael B (2016) A Non-invasive and Technically Non-intensive Method for Induction and Phenotyping of Experimental Bacterial Pneumonia in Mice. J Vis Exp :

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