Cell Signaling of Host Defense

由Michael B. Fessler博士领导的国立环境健康科学研究所校内研究部呼吸生物学实验室宿主防御小组大约在8周前，也就是2006年7月的最后一周才开始。最终，一项综合的先天免疫研究计划包括在基因工程小鼠的肺部炎症模型、体外细胞信号和蛋白质组学方面的努力。由于Fessler实验室最近才开放，迄今为止的大部分成就都是在招聘、采购、实验协议和培训方面取得的。例如，一名生物学家已经被雇用并开始培训。除此之外，2006年10月将有一名博士后开始工作，他将领导蛋白质组学研究，重点研究先天免疫信号。第二博士后职位的竞争申请已经收到，正在审查中。设备已购置，消耗品已入库。MTA已经完成并签署，允许即将接收三种基因工程小鼠品种进行再分化，而其他几种品种的最终批准正在等待。NIEHS机构研究委员会批准了一项允许从人类志愿者身上采集血液进行中性粒细胞分离的协议，并进行了轻微修改。动物护理和使用委员会的小鼠实验方案已获批准，第二项方案正在批准中，等待进行小的修改。费斯勒博士直接或间接地参与了三个独立的竞争性研究项目上个月提交给NIEHS主任？的挑战，其结果目前正在等待中。费斯勒博士的原始研究手稿？他在他之前的机构——国家犹太医学和研究中心完成的代表工作，最近被接受发表在《血液》杂志上，并将很快出现在网上。除此之外，另外两个第一作者手稿和几个共同作者手稿正在准备中。Fessler博士最近（2006年9月）在一个国际研究会议上发表了关于Rho GTPases在中性粒细胞活化中的作用的受邀研究报告，Grover会议关于肺循环，并于2006年10月被邀请作为维克森林大学的客座演讲者。

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.