Cell Signaling of Host Defense

由迈克尔·B·费斯勒医学博士领导的国家环境卫生科学研究所内壁研究部呼吸生物学实验室的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，一项涉及基因工程小鼠肺部炎症模型、体外细胞信号转导和蛋白质组学的综合先天免疫研究计划正在计划之中。由于费斯勒实验室最近刚刚开放，到目前为止，大多数成就都是在招聘、采购、实验方案和培训方面取得的。例如，已经聘请了一名生物学家，并开始了培训。除此之外，将于2006年10月开始的一名博士后研究员的成熟计划已经到位，他将带头开展一项专注于天然免疫信号的蛋白质组学工作。对第二个博士后职位的竞争性申请已经收到，并正在进行审查。已经购买和采购了设备，并储存了消耗品。MTA已经完成并签署，允许即将收到三个基因工程小鼠品系的重新衍生，而其他几个品系的最终批准正在等待中。NIEHS机构研究委员会的一项协议允许从人类志愿者身上采集血液进行中性粒细胞分离，该协议已获得批准，但有轻微的修改。动物保护和使用委员会关于小鼠实验的协议已经获得批准，第二个协议正在等待微小的修改。费斯勒博士直接或间接地为上个月提交给NIEHS所长S挑战赛的三个独立竞争性研究项目贡献了项目，这些项目的结果目前还在等待结果。费斯勒？S博士的一份原始研究手稿代表了他在之前的机构--国家犹太医学和研究中心完成的工作，最近被接受发表在《血液》杂志上，不久将在网上发表。除此之外，另外两份第一作者手稿和几份合著者手稿正在筹备中。Fessler博士最近(9/06)在格罗弗肺循环国际研究会议上就Rho GTP酶在中性粒细胞激活中的作用发表了应邀研究演讲，并于2006年10月被邀请为维克森林大学的特邀演讲人。 在实验领域，已经完成了几个动物和细胞培养实验。他汀类药物(HMG CoA还原酶抑制剂)在博莱霉素诱导的肺纤维化中的可能治疗作用的研究已经完成，其结果在撰写本文时尚未得出。关于高胆固醇饮食对内毒素和博莱霉素引起的肺部疾病的影响的其他研究已经开始。此外，确认和建立脂多糖致肺损伤模型的中试实验已经完成。关于脂多糖对细胞培养巨噬细胞中P53表达的影响的其他研究已经完成，其结果表明脂多糖抑制阿霉素诱导的P53表达。这些研究由科学家B·亚历克斯·梅里克博士进行，将为一项针对P53在先天性免疫中的作用的研究努力奠定基础，这项研究最终将包含动物研究和细胞培养研究元素。

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.