Personalized Cystic Fibrosis Therapy and Research Center

个性化囊性纤维化治疗和研究中心

• 批准号: 10672703
• 负责人: Raouf S. Amin
• 金额: $ 96.56万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10672703
• 关键词: Address; Adult; Adverse effects; Applications Grants; Autologous Transplantation; Basic Science; Biological; Biological Assay; Biological Models; Bronchoscopy; California; Caring; Caucasians; Cell secretion; Cells; Center Core Grants; Characteristics; Childhood; Chloride Channels; Chlorides; Chronic; Clinical; Clinical Research; Clinical Sciences; Collaborations; Conduct Clinical Trials; Core Facility; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; DNA Sequence Alteration; Databases; Dedications; Defect; Development; Diabetes Mellitus; Doctor of Philosophy; Duct (organ) structure; Duodenum; Endocrine; Endoscopy; Enteral; Epithelial Cells; Evaluation; Faculty; Fluids and Secretions; Fostering; Functional disorder; Funding; Future; Gases; Genetic Variation; Genotype; Goals; Grant; Healthcare; Hispanic; Home; Hospitals; Human; Individual; Institution; Institutional Review Boards; Intestines; Islet Cell; Islets of Langerhans; Laboratories; Liver; Lung; Lung Transplantation; Magnetic Resonance Imaging; Measurement; Medical center; Medicine; Minority Groups; Molecular; Mutation; Nasal Epithelium; National Institute of Diabetes and Digestive and Kidney Diseases; Nose; Not Hispanic or Latino; Onset of illness; Oral Poliovirus Vaccine; Organoids; Outcome; Pancreas; Patient Monitoring; Patients; Pediatric Hospitals; Pediatrics; Phenotype; Physicians; Population; Positioning Attribute; Predisposition; Productivity; Pulmonary Surfactants; Pulmonology; Quality of Care; Quality of life; Rectum; Regulator Genes; Reporting; Research; Research Activity; Research Personnel; Resources; Rotavirus Vaccines; Sampling; Scientist; Services; Site; Structure; Subgroup; Technology; Time; Total Pancreatectomy; Training; Translational Research; Underrepresented Minority; United States; Well in self; Xenon; accurate diagnosis; biobank; bronchial epithelium; cohort; coronavirus disease; cystic fibrosis patients; cystic fibrosis related diabetes; database of Genotypes and Phenotypes; demographics; early onset; electronic medical record system; gastrointestinal; health care service; health disparity; imaging study; improved; individual patient; interest; lung health; multidisciplinary; news; organ on a chip; patient population; personalized medicine; preservation; programs; pulmonary function; recruit; rectal; research facility; stem cell technology; stem cells; success; synergism; targeted treatment; therapy outcome

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.

项目概要-概述 囊性纤维化是由囊性纤维化跨膜传导的缺失或功能障碍引起的。 调节器（CFTR）氯离子通道。CFTR的缺陷与CFTR的遗传变异密切相关 基因是个体CF患者或CF患者群体内的亚组所特有的。因此 个性化的医疗方法有助于根据独特的分子生物学特性为个体CF患者定制护理。 和与其CFTR基因相关的表型特征。在此更新应用程序中，我们将促进 临床，转化和基础研究合作，以改善CF治疗和患者的生活质量， 个性化医疗，重点是解决CF少数群体。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-器官上 芯片核心。这将推动成功的治疗结果，并最大限度地减少慢性炎症的潜在不良影响。 治疗鉴于高效调节剂的最大益处是对肺功能的影响， 在CF相关糖尿病方面，CF-Organ-on-a Chip Core的重点将是研究糖尿病的机制 在多个基因突变中缺乏CFTR的导管和内分泌胰腺细胞中。我们将利用内部审查委员会 获批的基因型-表型数据库可用于临床和研究，以开发个性化的囊性 纤维化治疗和研究中心（PCFC）为个体患者（i）确定他/她对一种或多种抗纤维化药物的易感性， 特定形式的CF突变，和ii）采取措施减轻疾病的早期发作。最后，未来 CF研究为各种CFTR靶向治疗提供了潜力（即，CFTR调节剂）来治疗 CF的根本原因，目前有多种调节剂处于不同的开发阶段。