Craniosynostosis Network

颅缝早闭网络

基本信息

批准号：
8803592
负责人：
Patrick James Drew
金额：
$ 152.36万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-26 至 2020-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8803592
关键词：
Address Advisory Committees Anthropology Appearance Biological Biological Assay Biological Models Biology Bone Development Boston California Calvaria Cell Lineage Cell physiology Cells Cephalic Child Collaborations Commit Communities Complex Computer Simulation Congenital Abnormality Craniosynostosis Data Data Set Databases Development Developmental Biology Disease Embryo Environment Epidemiology Etiology Family Fostering France Funding Opportunities Gene Expression Gene Expression Regulation Genes Genetic Genomics Genotype Germany Goals Grant Growth Head Hospitals Human Image Image Analysis Individual Institution International Intervention Intracranial Hypertension Investigation Iowa Laboratories Leadership Life Live Birth Medical Medical center Mesenchymal Mesenchymal Stem Cells Modeling Molecular Morphogenesis Mus National Human Genome Research Institute Neurologic Deficit New York Operative Surgical Procedures Organ Osteoblasts Osteogenesis Parents Pathogenesis Pathway interactions Pediatric Hospitals Pennsylvania Phenotype Policies Postoperative Period Prevention Principal Investigator Process Productivity Program Research Project Grants Registries Regulation Research Research Design Research Personnel Role Scientist Shapes Site Spain Stem Cell Research Structural Congenital Anomalies Surgical sutures Syndrome System Systems Biology Technology Testing Texas Therapeutic Tissues United States National Institutes of Health Universities University Hospitals Validation Work base bone case control cohort coronal suture craniofacial cranium developmental genetics genetic variant genome wide association study improved induced pluripotent stem cell innovation insight malformation meetings morphometry mouse model multidisciplinary network models next generation sequencing novel osteoblast differentiation osteogenic overexpression postnatal premature prevent programs psychosocial public health relevance racial and ethnic reconstruction response screening skull abnormality statistics suture fusion therapeutic target

项目摘要

DESCRIPTION (provided by applicant): The long-term goal of the Program Project, Craniosynostosis Network, is to elucidate normal and abnormal craniofacial biology to ultimately improve the treatment of craniofacial disorders. Craniosynostosis (CS) and other skull abnormalities are among the most common human malformations and usually require surgical and medical intervention. Our Network will integrate the efforts of scientists with diverse expertise including anthropology, morphometry, imaging, birth defects, developmental biology, genetics, genomics, epidemiology, statistics, & system biology to explore the determinants of the fate of the relevant mesenchymal progenitor cells, and how abnormalities in the processes of osteogenesis contribute to disorders such as global skull growth abnormality, premature closure of sutures, in particular the coronal suture. We will use humans and mouse model systems to study normal development and malformations that characterize birth defects such as Apert, Crouzon, and Muenke syndromes & coronal nonsyndromic craniosynostosis. Our research design will be multidisciplinary including imaging, genomics, computational modeling & stem cell research; and evolutionary, developmental, & systems biology. Our approach will be hypothesis and discovery-driven, and we will generate and integrate a wide variety of human genomic, imaging, & laboratory data. The Network will be based at Mount Sinai Medical Center with the contact Principal Investigator (PI), Ethylin Wang Jabs, and multiple PIs, Inga Peter, Eric Schadt and Ihor Lemischka, and at Pennsylvania State University with MPIs Joan Richtsmeier, Patrick Drew, and Reuben Kraft. Our international and national collaborating institutions include: Hospital Necker-Enfants Maladies (France), University Hospital Heidelberg (Germany), and Hospital Sant Joan de Deu (Spain); Oxford University (UK), the International Craniosynostosis Consortium at University of California at Davis; New York State birth defect registry involved with the National Birth Defects Prevention Study based at Univ. of Iowa, directed by MPI Paul Romitti; New York University, Pennsylvania State Milton S. Hershey Medical Center; Boston Children's Hospital; Yale University, Univ. of Texas at Southwestern, and Johns Hopkins University. Our Advisory Committee includes experts in developmental biology, genomics, and system biology: Philippe Soriano from Mount Sinai Medical Center, James Sharpe of the Centre for Genomic Regulation, Barcelona, Spain, Alec Wilson of NIH NHGRI, & Richard Bonneau of New York University. Our proposal consists of Project I "From Skull Shape to Cell Activity in Coronal Craniosynostosis", Project II "Genomics Approaches to Coronal Nonsyndromic Craniosynostosis", & Project III "Systems Biology of Bone in Coronal Nonsyndromic Craniosynostosis"; and two Cores: Administrative Core A and Molecular/Analytic Core B. The investigators, by engaging as an integrated group in the study of complex biological networks, and by utilizing innovative and state-of-the-art technologies, will foster an outstanding research environment. The Network is strongly committed to sharing & disseminating our findings to the scientific community at large.

描述（由申请人提供）：颅缝早闭网络项目的长期目标是阐明正常和异常的颅面生物学，以最终改善颅面早闭 (CS) 和其他颅骨异常的治疗。我们的网络将整合具有不同专业知识的科学家的努力，包括人类学、形态测量学、成像、出生缺陷、发育生物学、基因组学、基因组学、流行病学、统计学和系统生物学，探索相关间充质祖细胞命运的决定因素，以及成骨过程中的异常如何导致整体颅骨生长异常、缝线过早闭合等疾病，特别是我们将使用人类和小鼠模型系统来研究具有出生缺陷特征的正常发育和畸形，例如阿佩尔综合征、克鲁宗综合征和穆恩克综合征以及冠状非综合征。我们的研究设计将是多学科的，包括成像、基因组学、计算模型和干细胞研究以及进化、发育和系统生物学；我们的方法将是假设和发现驱动的，我们将产生和整合各种各样的人类。该网络将设在西奈山医疗中心，联系人为首席研究员 (PI) Ethylin Wang Jabs 和多名 PI Inga Peter、Eric。 Schadt 和 Ihor Lemischka，以及宾夕法尼亚州立大学的 MPI Joan Richtsmeier、Patrick Drew 和 Reuben Kraft 我们的国际和国内合作机构包括：Necker-Enfants Maladies 医院（法国）、海德堡大学医院（德国）和 Sant Joan 医院。 de Deu（西班牙）；牛津大学（英国）、加州大学戴维斯分校国际颅缝早闭联盟参与；与爱荷华大学国家出生缺陷预防研究合作，由 MPI Paul Romitti 领导；波士顿儿童医院、德克萨斯大学西南分校和我们的顾问委员会包括发育生物学、基因组学和系统生物学方面的专家：西奈山医学中心的 Philippe Soriano、西班牙巴塞罗那基因组调控中心的 James Sharpe、美国国立卫生研究院的 Alec Wilson NHGRI 和纽约大学的 Richard Bonneau。我们的提案包括项目 I“从颅骨形状到冠状颅缝早闭的细胞活性”、项目 II“冠状非综合征性颅缝早闭的基因组学方法”和项目 III“冠状非综合征性骨的系统生物学”。颅缝早闭”；以及两个核心：管理核心 A 和分子/分析核心 B。作为一个综合团体参与复杂生物网络的研究，并利用创新和最先进的技术，该网络将坚定地致力于向科学界分享和传播我们的研究结果。大的。