Craniosynostosis Network

颅缝早闭网络

• 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
• 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

 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(申请人提供)：该计划项目的长期目标，颅缝融合网络，是为了阐明正常和异常的颅面生物学，最终改善颅面疾病的治疗。颅缝早闭(CS)和其他颅骨畸形是最常见的人类畸形之一，通常需要手术和医学干预。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、遗传学、基因组学、流行病学、统计学和系统生物学，以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全球颅骨生长异常、缝合过早关闭，特别是冠状缝合等疾病。我们将使用人类和小鼠模型系统来研究以出生缺陷为特征的正常发育和畸形，如Apert、Crouzon和Muenke综合征&冠状非综合征颅缝融合。我们的研究设计将是多学科的，包括成像、基因组学、计算建模和干细胞研究；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，我们将生成和整合各种各样的人类基因组、成像和实验室数据。该网络将设在西奈山医疗中心，联络首席调查员(PI)Etherylin 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Ruben Kraft。我们的国际和国内合作机构包括：Necker-Enfants医院(法国)、海德堡大学医院(德国)和圣琼医院(西班牙)；牛津大学(英国)、加州大学戴维斯分校的国际颅脑融合联合会；纽约州出生缺陷登记机构；纽约州出生缺陷登记机构；纽约州新生儿出生缺陷预防研究；纽约州出生缺陷预防研究。由MPI Paul Romitti指导；纽约大学宾夕法尼亚州立大学米尔顿·S·赫尔希医学中心；波士顿儿童医院；耶鲁大学，大学。德克萨斯大学西南分校和约翰霍普金斯大学。我们的咨询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、NIH NHGRI的Alec Wilson和纽约大学的Richard Bonneau。我们的建议包括项目I“从头骨形状到冠状融合中的细胞活性”、项目II“冠状非综合征合并颅骨融合的基因组学方法”和项目III“冠状非综合征合并中的骨的系统生物学”，以及两个核心：管理核心A和分子/分析核心B。研究人员将作为一个综合小组参与复杂生物网络的研究，并利用创新和最先进的技术，营造一个优秀的研究环境。该网络坚定地致力于向整个科学界分享和传播我们的研究成果。