Personalized Cystic Fibrosis Therapy and Research Center

项目摘要-概述 囊性纤维化是由于囊性纤维化跨膜电导缺失或功能障碍所致 调节剂(CFTR)氯通道。Cftr基因缺陷与cftr基因变异密切相关 这些基因是个别CF患者或CF患者群体中的亚群所特有的。因此，一个 个性化的医疗方法有助于根据独特的分子为患者个体化护理 以及与其CFTR基因相关的表型特征。在本次续费申请中，我们将推广 临床、翻译和基础研究合作，通过以下方式提高CF治疗和患者的生活质量 个性化医疗，重点是针对CF少数民族人群。这一目标将通过 3个集成核心：个性化临床核心、个性化模型系统核心和新的CF-Organ-on-a 芯片核心。这将推动成功的治疗结果，并将慢性病的潜在不良影响降至最低 治疗。鉴于高效调节剂的最大益处是对肺功能的影响，但几乎没有明显的影响 在与CF相关的糖尿病方面，CF-Organ-On-a芯片核心的重点将是糖尿病机制的研究 在导管和内分泌细胞中缺乏CFTR的多个基因突变。我们将利用IRB 批准的基因-表型数据库可用于临床和研究，以开发个性化囊性病变 纤维化治疗和研究中心(PCFC)，供个别患者(I)确定其对 (2)采取措施减轻疾病的早期发病。最后，中国的未来 Cf研究提供了各种针对cftr的治疗方法(即cftr调节剂)，以治疗 CF的根本原因，目前有多个调制器处于不同的开发阶段。

PROJECT SUMMARY – OVERVIEW Cystic Fibrosis results from the absence or dysfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) chloride channel. Defects in CFTR are strongly associated with genetic variations in the CFTR gene that are unique to individual CF patients or to subgroups within the CF patient population. Thus, a personalized medicine approach helps customize care to individual CF patients based on the unique molecular and phenotypic characteristics associated with their CFTR gene. In this renewal application we will promote clinical, translational, and basic research collaboration to improve CF therapy and patient quality of life through personalized medicine with an emphasis to address CF minority population. This goal will be achieved through 3 integrated cores: Personalized Clinical Core, Personalized Model Systems Core and the new CF-Organ-on-a Chip Core. This will drive successful therapeutic outcomes and minimize potential adverse effects of chronic therapies. Given that the largest benefit of highly effective modulators is on lung function with little tangible effect on CF related diabetes, the focus of the CF-Organ-on-a Chip Core will be the study of mechanisms of diabetes in ductal and endocrine pancreatic cells lacking CFTR in multiple genetic mutations. We will leverage an IRB approved genotype-phenotype database available for clinical and research use, to develop Personalized Cystic Fibrosis Therapy and Research Center (PCFC) for individual patients to (i) determine his/her susceptibility to a particular form of CF mutation, and ii) take steps to mitigate the early onset of the disease. Finally, the future of CF research offers the potential for a variety of CFTR-targeted therapies (i e., CFTR modulators) to treat the underlying cause of CF, with multiple modulators currently in different stages of development.