Translational Research Center to Expedite Novel Therapies in Cystic Fibrosis

描述(由申请人提供)：这个P30囊性纤维化(CF)研究和翻译核心中心(CFRTC)位于华盛顿大学医学院(UWSOM)及其附属机构西雅图儿童研究所(SCRI)。这一拟议的P30中心计划增强了这些机构现有的强大的基础和临床研究基础，目前研究资金的直接成本超过2000万美元，与CF相关的基础设施资金额外增加500万美元，并包括19个部门和/或部门的48名UWSOM调查人员。UWSOM在与CF相关的翻译研究方面有着悠久的卓越历史，吸入型妥布霉素(TOBI(R))的成功开发和CFF支持的治疗开发网络的领先就是明证。P30的研究将集中于四个具体目标：1)提供资源和专业知识，以加快开发有前景的新治疗方法，以纠正CFTR功能障碍及其继发性后果，包括消化不良和营养不良、肝胆疾病和慢性肺部疾病。2)促进国内和国际P-30生物医学核心之间的合作，通过共享链接到临床数据库的人类和细菌储存库来加强转译研究。利用这些共享的标本和数据资源来开发改进的分析、生物标记物和临床结果衡量标准。3)加强对囊性纤维化患者胃肠道和呼吸道中不断演变的细菌生态系统和由此产生的宿主反应的了解，以及这些相互作用是如何 影响健康。4)更好地了解CFTR功能障碍的代谢和炎症后果。该中心将由共同PD的Bonnie Ramsey医学博士和E.Peter Greenberg博士领导，他们都是在各自的临床研究和细菌发病机制领域得到国际认可的CF研究人员。他们将得到其他主要领导的支持：医学、微生物学、基因组科学和免疫学教授塞缪尔·米勒医学博士，比较医学系副教授查尔斯·弗雷斯特，DVM，SCD，医学和儿科学教授克里斯托弗·戈斯，公共卫生硕士，医学教授普拉迪普·辛格博士。该中心将由一个行政核心(拉姆齐和格林伯格主任)和四个生物医学核心组成：微生物学(格林伯格主任)、基因组学(米勒，主任)、宿主反应(弗雷斯特，主任)和临床翻译(克里斯托弗·戈斯和拉姆齐，主任)。核心中心将运行一项由普拉迪普·辛格博士领导的试点和可行性(P&F)计划。目前的提案中包括三个新核准的P&F项目，这些项目是通过竞争程序选定的，并由内部咨询委员会核准。在资助期间，核心中心将专注于开发几种新的治疗方法，以改善CF患者的整体健康。

DESCRIPTION (provided by applicant): This P30 Cystic Fibrosis (CF) Research and Translational Core Center (CFRTC) is located at the University of Washington School of Medicine (UWSOM) and its affiliated institution, Seattle Children's Research Institute (SCRI). This proposed P30 center program enhances an existing robust basic and clinical research base at these institutions totally over $20 million direct costs in current research funding and an additional $5 million in CF related infrastructure funding, and includes 48 UWSOM investigators in 19 departments and/or divisions. The UWSOM has a long history of excellence in CF related translational research as evidenced by the successful development of inhaled tobramycin (TOBI(r)) and the leadership in the CFF supported Therapeutics Development Network. The research for this P30 will focus on four Specific Aims: 1) Provide resources and expertise to expedite development of promising new therapeutic approaches to correct dysfunctional CFTR and its secondary consequences including maldigestion and malnutrition, hepatobiliary disease and chronic lung disease. 2) Foster collaboration across P-30 biomedical cores, nationally and internationally to enhance translational research through sharing of human and bacterial repositories linked to clinical databases. Utilize these shared specimen and data resources to develop improved assays, biomarkers and clinical outcome measures. 3) Enhance understanding of the evolving bacterial ecosystems and resultant host response in the gastrointestinal and respiratory tracts of patients with cystic fibrosis and how these interactions impact health. 4) Better understand the metabolic and inflammatory consequences of CFTR dysfunction. The center will be led by Co-PD's, Bonnie Ramsey, MD and E. Peter Greenberg PhD, CF investigators both internationally recognized in their respective areas of clinical research and bacterial pathogenesis. They will be supported by other key leadership: Samuel Miller MD, Professor of Medicine, Microbiology, Genome Sciences, and Immunology, Charles Frevert, DVM, ScD, Associate Professor in the Department of Comparative Medicine, Christopher Goss MD, MPH, Professor of Medicine and Pediatrics, and Pradeep Singh MD, Professor of Medicine. The center will consist of an Administrative Core (Ramsey and Greenberg, Directors) and four biomedical cores, Microbiology (Greenberg, Director), Genomics (Miller, Director), Host Response (Frevert, Director) and Clinical Translational (Christopher Goss and Ramsey, Directors). The core centers will operate a Pilot and Feasibility (P&F) program led by Dr. Pradeep Singh. Three newly approved P&F projects are included in the current proposal chosen through a competitive process and approved by the Internal Advisory Board. During the funding period, the core center will focus on development of several novel therapeutic approaches to improve overall health for patients with CF.