Cell Signaling of Host Defense

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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.