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引起的 调节剂 (CFTR) 氯离子通道的缺陷与 CFTR 的遗传变异密切相关。 基因对于个体 CF 患者或 CF 患者群体中的亚组来说是独特的。 个性化医疗方法有助于根据独特的分子特征为个体 CF 患者定制护理 以及与其 CFTR 基因相关的表型特征。在此更新应用中，我们将推广。 临床、转化和基础研究合作，通过以下方式改善 CF 治疗和患者生活质量 个性化医疗，重点是解决 CF 少数群体这一目标将通过以下方式实现。 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最大限度地减少慢性病的潜在不利影响。 鉴于高效调节剂的最大好处是对肺功能的影响很小。 关于CF相关的糖尿病，CF-Organ-on-a Chip Core的重点将是糖尿病机制的研究 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 IRB。 批准的基因型-表型数据库可用于临床和研究用途，以开发个性化囊性 纤维化治疗和研究中心 (PCFC) 为个体患者提供 (i) 确定他/她对某种药物的易感性 特定形式的 CF 突变，以及 ii) 采取措施减轻疾病的早期发作 最后，未来。 CF 研究为多种 CFTR 靶向疗法（即 CFTR 调节剂）提供了治疗以下疾病的潜力： CF 的根本原因，目前有多种调节剂处于不同的开发阶段。