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 only began approximately 8 weeks ago, in the final week of July, 2006. Ultimately, an integrated innate immunity research program involving efforts in lung inflammation models in genetically engineered mice, in vitro cell signaling, and proteomics is planned. Because of the very recent opening of Fessler laboratory, most of the accomplishments to date have been in the area of hiring, purchasing, experimental protocols, and training. For example, a biologist has been hired and training commenced. In addition to this, mature plans are in place for a postdoctoral fellow to commence in October, 2006, who will spearhead a proteomics effort focused on innate immunity signaling. Competitive applications for a second postdoctoral position have been received and are being examined. Equipment has been purchased and procured, and consumable supplies stocked. An MTA has been completed and signed, permitting imminent receipt of three genetically engineered mouse strains for rederivation, while final approval on several other strains is pending. An NIEHS Institutional Research Board protocol permitting blood collection from human volunteers for neutrophil isolation has been approved with minor amendments. An Animal Care and Use Committee protocol for mouse experimentation has been approved, and a second protocol is approved pending minor amendments. Dr. Fessler contributed projects directly or indirectly to three independent competititive research programs submitted last month for the NIEHS Director?s Challenge, the results of which are currently pending. An original research manuscript of Dr. Fessler?s representing work completed at his previous institution, National Jewish Medical and Research Center, was recently accepted for publication in Blood, and will shortly appear online. In addition to this, two other first-author manuscripts and several co-author manuscripts are in preparation. Dr. Fessler recently (9/06) delivered an invited research talk on the role of Rho GTPases in neutrophil activation at an international research meeting, the Grover Conference on the Pulmonary Circulation, and has been invited as a guest speaker at Wake Forest University in October, 2006.? ? In the realm of experiments, several animal and cell culture experiments have already been completed. A study of the possible therapeutic role of statins (HMG CoA reductase inhibitors) in bleomycin-induced lung fibrosis has been completed, the results of which are pending at the time of this writing. Additional studies of the effect of a high-cholesterol diet on lipopolysaccharide and bleomycin-induced lung disease have been commenced. In addition, pilot experiments to confirm and establish a model of lipopolysaccharide-induced lung injury have been completed. Other studies of the effect of lipopolysaccharide on p53 expression in cell culture macrophages have been completed, the results of which suggest that LPS suppresses doxorubicin-induced p53 expression. These studies, conducted by staff scientist B. Alex Merrick, PhD, will lay the groundwork for a research effort targeting the role of p53 in innate immunity, which will ultimately have animal research and cell culture research elements.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES102005-01
Application #
7330700
Study Section
(LRB)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2006
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Fessler, Michael B (2018) The challenges and promise of targeting the Liver X Receptors for treatment of inflammatory disease. Pharmacol Ther 181:1-12
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 (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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