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RESEARCH ON FUNCTIONAL GENOMICS, IMAGE ANALYSIS AND RESCUE OF CLEFT PALATE

功能基因组学、图像分析及腭裂抢救研究

基本信息

批准号：
8463414
负责人：
Yang Chai
金额：
$ 39.13万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-21 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8463414
关键词：
Address Animal Model California Candidate Disease Gene Cells Cleft Palate Collaborations Congenital Abnormality Coupled Data Data Collection Databases Defect Development Face Future Gene Expression Gene Expression Profiling Gene Targeting Genes Genomics Human Image Image Analysis Institutes Intervention Investigation Laboratories Mesenchyme Modeling Molecular Molecular Profiling Mucous body substance Mus Neural Crest Palate Population Prevention Principal Investigator Recording of previous events Regulator Genes Research Resources Scientist Signal Pathway Signal Transduction Signaling Molecule Technology Testing Therapeutic Translational Research Work Yang base clinically relevant craniofacial design functional genomics high throughput analysis in vivo malformation mutant palatogenesis prevent programs public health relevance

项目摘要

DESCRIPTION (provided by applicant): The development of the Face Base Consortium calls for a comprehensive research collaboration to facilitate data collection, organization, and optimized utilization of new and existing data on mid-facial development and malformations. Our laboratory has a long history of investigating the molecular and cellular mechanism of cleft palate. We have developed a proposal that builds on our strength and will focus on genomic and imaging analysis of selected and highly clinically relevant cleft palate animal models. Specifically, we will use the Tgfb, Tgfbr, Smad4, Msx1 and Fgfr2 mutant animal models that represent complete and sub-mucous cleft palate defects in humans as our entry point. Taking advantage of these animal models, we will work closely with several scientists to address the regulatory mechanism of CNC cell fate determination. Specifically, working with Dr. Marianne Bronner-Fraser at California Institute of Technology (Caltech), we will investigate whether the neural crest gene regulatory network of traditional vertebrate models is conserved and may exert its regulatory function during palatogenesis. In collaboration with Dr. Joseph Hacia at USC, we will discover critical components of the Tgf-b signaling network that are specifically involved in regulating the fate of CNC cells during palatogenesis. Working with Dr. Scott Fraser at Caltech, we will generate comprehensive and dynamic three-dimensional images of palatogenesis and malformations using microMRI and microCT. Finally, we have developed a strategy to screen for specific points of intervention within the gene regulatory network that will allow us to develop therapeutic strategies to prevent and rescue cleft palate. Our collective effort will not only generate tremendous resources for the Face Base Consortium but will also offer opportunities for extensive collaborations for future translational research on craniofacial birth defects.

描述（由申请人提供）：Face Base Consortium的发展要求进行全面的研究合作，以促进数据收集，组织和优化利用关于面中部发育和畸形的新数据和现有数据。我们实验室在腭裂的分子和细胞机制研究方面有着悠久的历史。我们已经制定了一项建议，建立在我们的实力，并将重点放在基因组和成像分析选定的和高度临床相关的腭裂动物模型。具体来说，我们将使用Tgfb，Tgfbr，Smad 4，Msx 1和Fgfr 2突变动物模型，代表人类完全和粘膜下腭裂缺陷作为我们的切入点。利用这些动物模型，我们将与几位科学家密切合作，解决CNC细胞命运决定的调控机制。具体来说，我们将与加州理工学院（Caltech）的Marianne Bronner-Fraser博士合作，研究传统脊椎动物模型的神经嵴基因调控网络是否保守，并可能在腭发育过程中发挥其调控功能。与南加州大学的Joseph Hacia博士合作，我们将发现Tgf-b信号网络的关键组成部分，这些组成部分专门参与调节腭发育过程中CNC细胞的命运。与加州理工学院的Scott Fraser博士合作，我们将使用microMRI和microCT生成腭发育和畸形的全面动态三维图像。最后，我们已经开发出一种策略来筛选基因调控网络中的特定干预点，这将使我们能够开发预防和挽救腭裂的治疗策略。我们的共同努力不仅将为Face Base Consortium带来巨大的资源，还将为未来颅面出生缺陷的转化研究提供广泛合作的机会。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Convergent genesis of an adult neural crest-like dermal stem cell from distinct developmental origins.

DOI：
10.1002/stem.525
发表时间：
2010-11
期刊：
STEM CELLS
影响因子：
5.2
作者：
Jinno, Hiroyuki;Morozova, Olena;Jones, Karen L.;Biernaskie, Jeffrey A.;Paris, Maryline;Hosokawa, Ryoichi;Rudnicki, Michael A.;Chai, Yang;Rossi, Fabio;Marra, Marco A.;Miller, Freda D.
通讯作者：
Miller, Freda D.

Roles of BMP signaling pathway in lip and palate development.