Monocyte Pyrin Expression in Human Sepsis

人类脓毒症中单核细胞 Pyrin 的表达

• 批准号: 7134137
• 负责人: MARK W HALL
• 金额: $ 13.23万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-24 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7134137
• 关键词: actinomycin; adolescence (12-20); child (0-11); clinical research; cytoskeletal proteins; densitometry; gene expression; genetic polymorphism; genetic regulatory element; human genetic material tag; human mortality; human subject; immunogenetics; inflammation; lipopolysaccharides; messenger RNA; monocyte; protein quantitation /detection; septic shock; septicemia; western blottings

DESCRIPTION (provided by applicant): This submission describes a comprehensive 3 year training program in molecular biology and molecular genetics designed to provide Dr. Mark W. Hall with the tools to become an outstanding, independent physician-scientist. This training, combined with his K12 support to date, will give him the necessary skills to investigate the regulation of inflammation in pediatric sepsis. Dr. Hall completed his medical training in Pediatrics and Pediatric Critical Care Medicine at Children's Hospital of Pittsburgh and is now Assistant Professor at The Ohio State University / Columbus Children's Hospital. Dr. Mark D. Wewers, a leader in the field of innate immunobiology, will serve as Dr. Hall's sponsor and mentor. Dr. Hall has generated, with the help of Dr. Wewers and his laboratory staff, preliminary data from a cohort of 28 children with sepsis-induced organ failure. These data show that monocytes in survivors demonstrate a marked downregulation of mRNA for the protein pyrin compared to nonsurvivors. Pyrin is an important regulatory protein which is associated with inflammation in the disease familial Mediterranean fever. Pyrin and its gene MEFV have not been described in this context before. In the course of the award period we expect to: 1) understand the associations between monocyte MEFV mRNA expression, monocyte pyrin protein expression, and mortality in the setting of pediatric severe sepsis/septic shock, 2) understand the role of mRNA production versus mRNA degradation in determining MEFV mRNA levels in survivors versus nonsurvivors of pediatric severe sepsis/septic shock, and 3) test the hypothesis that reduction in monocyte MEFV mRNA expression in the setting of pediatric severe sepsis/septic shock is associated with the presence of a cis-acting polymorphism in the MEFV gene. In order to accomplish this final goal, and to provide Dr.Hall with a robust foundation in molecular genetics, he will spend time in training and experimentation in the laboratory of Dr. Wolfgang Sadee, a world expert in the area of regulatory genetic polymorphisms. The combined facilities of Columbus Children's Research Institute, the Davis Heart and Lung Research Institute, and The Ohio State University offer an unparalleled array of scientific resources and provide an ideal setting for Dr. Hall's academic and scientific development. (End of Abstract)

描述（由申请人提供）： 该提交描述了一项针对分子生物学和分子遗传学的全面的3年培训计划，旨在为Mark W. Hall博士提供成为一种杰出的独立医师 - 科学家的工具。这项培训及其迄今为止的K12支持，将为他提供必要的技能，以调查小儿脓毒症的炎症调节。霍尔博士在匹兹堡儿童医院完成了他在儿科和小儿重症监护医学方面的医学培训，现在是俄亥俄州立大学 /哥伦布儿童医院的助理教授。 先天免疫生物学领域的领导者Mark D. Wewers博士将担任Hall博士的赞助商和导师。霍尔博士在Wewers博士及其实验室工作人员的帮助下产生了来自28名败血症器官衰竭儿童的初步数据。这些数据表明，与非生存者相比，幸存者中的单核细胞表明蛋白pyrin的mRNA明显下调。吡啶是一种重要的调节蛋白，与家族性地中海疾病中的炎症有关。 pyrin及其基因MEFV以前尚未在这种情况下进行描述。 In the course of the award period we expect to: 1) understand the associations between monocyte MEFV mRNA expression, monocyte pyrin protein expression, and mortality in the setting of pediatric severe sepsis/septic shock, 2) understand the role of mRNA production versus mRNA degradation in determining MEFV mRNA levels in survivors versus nonsurvivors of pediatric severe sepsis/septic shock, and 3) test the假设在小儿严重的败血症/败血性休克的情况下，单核细胞MEFV mRNA表达降低与MEFV基因中的顺式作用多态性存在有关。为了实现这一最终目标，并为Hall博士提供了分子遗传学的强大基础，他将花时间在监管遗传多态性领域的世界专家Wolfgang Sadee博士的实验室进行培训和实验。哥伦布儿童研究所，戴维斯心脏和肺部研究所以及俄亥俄州立大学的合并设施提供了无与伦比的科学资源，并为霍尔博士的学术和科学发展提供了理想的环境。 （抽象的结尾）