Clinical Center: ChiLDReN (Childhood Liver Disease Research Network)

临床中心：ChiLDReN（儿童肝病研究网络）

• 批准号: 8773967
• 负责人: PETER Frank WHITINGTON
• 金额: $ 37.43万
• 依托单位: LURIE CHILDREN'S HOSPITAL OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-15 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8773967
• 关键词: Accounting; Affect; Alagille Syndrome; Animal Model; Area; Bile Acid Biosynthesis Pathway; Biliary Atresia; Biological; Biological Markers; Child; Childhood; Chronic; Clinical; Clinical Data; Clinical Research; Clinical Trials; Cystic Fibrosis; Data; Databases; Defect; Development; Diagnosis; Disease; Education; Elements; Etiology; Fibrosis; Functional disorder; Future; Gene Expression; Genetic Predisposition to Disease; Goals; Hepatic; Incidence; Individual; Infant; Investigation; Leadership; Left; Link; Live Birth; Liver; Liver diseases; Measures; Mission; Mitochondria; Morbidity - disease rate; Names; Natural History; Other Genetics; Participant; Pathogenesis; Patients; Performance; Plasma; Principal Investigator; Process; Production; Progressive intrahepatic cholestasis; Public Health; Publishing; Records; Recruitment Activity; Research; Research Design; Research Methodology; Research Personnel; Resources; Role; Signal Transduction; Specimen; Staging; Testing; Therapeutic; Translational Research; United States; Work; alpha 1-Antitrypsin Deficiency; biobank; burden of illness; cohort; early childhood; epigenomics; expectation; fibrogenesis; improved; infancy; liver transplantation; mortality; neonatal hepatitis; neonate; novel; operation; osteopontin; outcome forecast; programs; public health relevance; research study; response; response to injury; smoothened signaling pathway; success

DESCRIPTION (provided by applicant): Liver disease is a major cause of infant and childhood morbidity and mortality. The diseases comprising "pediatric liver diseases" are individually rare, which has hindered the study of their causes/pathophysiologies. As a result of this basic defect in understanding effective therapeutic strategies are lacking for most of them. This in turn results in many children with progressing to end-stage liver disease necessitating orthotopic liver transplantation. Pediatric liver transplants comprise approximately 10% of all liver transplants performed, and the indications for most of them lie among the diseases to be studied in the Childhood Liver Disease Research Network (ChiLDReN). This network combines the efforts of several large and individually successful clinical research enterprises to recruit subjects and carry them through rigorous clinical studies and trials with the expectation of establishing well-characterized patient cohorts that can be followed through the natural history of their disease process and which can be accessed for trials of emerging therapies. In addition, the biological specimens linked to clinical data provide the fuel for studies of etiology (genetic and other) and the influences of gene expression and epigenomics on disease expression and progression, as well as response to therapy. We propose to participate in ChiLDReN as a center wherein investigators have substantial expertise in several of the key areas of investigation within the consortium as a whole. Our center has been one of the top contributors of subjects to every study undertaken by ChiLDReN (and its predecessor consortia) over the term of its existence. We expect to continue to contribute substantially to the performance of ChiLDReN in achieving its goal of successfully eliminating pediatric liver disease as a major cause of infant and childhood morbidity and mortality. The specific aims at our center include: a) to participate fully as a leading clinical center in ChiLDReN; and b) to utilize the currently available specimens from the ChiLDReN biorepository to develop a novel biomarker for fibrosis and determine if activation of the developmental signaling pathway hedgehog contributes to the development of fibrosis in biliary atresia.

描述（由申请人提供）：肝病是婴儿和儿童发病和死亡的主要原因。包括“小儿肝病”在内的疾病个别罕见，这阻碍了对其病因/病理生理学的研究。由于这种理解上的基本缺陷，他们中的大多数人缺乏有效的治疗策略。这反过来导致许多儿童进展为终末期肝病，需要进行原位肝移植。儿童肝移植约占所有肝移植的 10%，其中大多数的适应症属于儿童肝病研究网络 (ChiLDReN) 正在研究的疾病。该网络结合了几家大型且各自成功的临床研究企业的努力，招募受试者并让他们进行严格的临床研究和试验，期望建立特征良好的患者队列，可以跟踪其疾病过程的自然史，并可用于新兴疗法的试验。此外，与临床数据相关的生物样本为病因学（遗传和其他）以及基因表达和表观基因组学对疾病表达和进展以及治疗反应的影响的研究提供了燃料。我们建议以 ChiLDReN 为中心参与其中，其中研究人员在整个联盟的几个关键研究领域拥有丰富的专业知识。自成立以来，我们中心一直是 ChiLDReN（及其前身联盟）开展的每项研究的主要课题贡献者之一。我们期望继续为 ChiLDReN 的绩效做出重大贡献，以实现其成功消除小儿肝病这一婴儿和儿童发病和死亡主要原因的目标。我们中心的具体目标包括： a) 作为领先的 ChiLDReN 临床中心全面参与； b) 利用 ChiLDReN 生物样本库中现有的样本开发一种新的纤维化生物标志物，并确定发育信号通路 hedgehog 的激活是否有助于胆道闭锁纤维化的发展。