CLEAR Consortium: Discovering the Developmental Mechanisms of Trachea-Esophageal Birth Defects

CLEAR联盟：发现气管-食管先天缺陷的发育机制

基本信息

批准号：
10647822
负责人：
Wendy K Chung
金额：
$ 160.23万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-15 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10647822
关键词：
Academic Medical Centers Acceleration Address Animal Model Animals Automobile Driving Award Bioinformatics Birth Breathing Cells Cellular biology Clinical Clustered Regularly Interspaced Short Palindromic Repeats Communication Congenital Abnormality Databases Defect Development Diagnosis Doctor of Philosophy Educational workshop Embryology Esophageal Atresia Esophagus Etiology Event Fetal Development Gene Mutation Genes Genetic Genomics Genotype Goals Human In Vitro Institution Investigation Life Link Magnetic Resonance Imaging Methods Mining Modeling Molecular Morphogenesis Mutation Newborn Infant Organoids Paper Patients Pediatric Hospitals Phenotype Primitive foregut structure Publishing Registries Reporting Research Personnel Resources Role Scientist Surgeon Techniques Technology Testing Tissue Engineering Tissues Trachea Tracheoesophageal Fistula Tube United States National Institutes of Health Variant Xenopus causal variant comorbidity data integration embryo tissue experience feeding genome sequencing improved innovation meetings mouse genetics multidisciplinary neonatal magnetic resonance imaging novel patient advocacy group prevent programs repaired risk variant stem cells success synergism web site

项目摘要

OVERALL | PROJECT SUMMARY The goal of the CLEAR Consortium is to elucidate the developmental and genetic mechanisms of trachea- esophageal birth defects (TEDs) to better understand their etiology, enhance diagnosis, improve treatment, and inform strategies to generate tissue in vitro that might ultimately be used for repair. The trachea and esophagus arise from the separation of a common foregut tube during early fetal development. Defects in trachea- esophageal development cause a spectrum of life-threatening TEDs, which occur in ~1:3500 births and prevent proper breathing and feeding in newborn infants. Gene mutations are known to cause TEDs but have only been identified in ~15% of cases and how these cause congenital malformations is poorly defined. To address this unmet need we have assembled an experienced and highly collaborative multi-disciplinary team of clinicians, surgeons, geneticists, computational scientists, and developmental and stem cell biologists that use an innovative combination of patient genome sequencing, neonatal MRI, animal models, quantitative cell biology, single cell genomics, CRISPR gene editing and human PSCs-derived organoids to study TEDs. This Multi-PI project centered at Cincinnati Children’s Hospital (CCHMC) and Columbia University Medical Center (CUMC) is led by Wendy Chung MD PhD (CUMC), Paul Kingma MD PhD (CCHMC), Yufeng Shen PhD (CUMC), James Wells PhD (CCHMC) and Aaron Zorn PhD (contact PI; CCHMC). Our program has 3 projects linked together by an Integrated Genomics Core. Project-1: Comprehensive phenotypic and genetic assessment of TED patients. Project-2: Defining the developmental mechanisms of TEDs in animal models. Project-3: Modeling EA in human PSC-derived embryonic tissues.

总体|项目摘要明确财团的目的是阐明气管的发育和遗传机制食管生育缺陷（TEDS），以更好地了解其病因，增强诊断，改善治疗和告知在体外生成组织的策略，该组织最终可用于修复。气管和食道源于早期胎儿发育过程中普通管的分离。气管缺陷食道发育会导致危及生命的TED，这些TED发生在〜1：3500中，并防止适当的呼吸和喂食新生婴儿。已知基因突变会引起TED，但仅是在〜15％的病例中确定，这些原因如何定义为先天性畸形。解决这个问题未满足的需求我们聚集了一个经验和高度协作的临床医生的多学科团队，外科医生，遗传学家，计算科学家以及使用的发育和干细胞生物学家患者基因组测序，新生儿MRI，动物模型，定量细胞生物学的创新组合，单细胞基因组学，CRISPR基因编辑和人类PSC衍生的类器官研究TED。这个多pi 以辛辛那提儿童医院（CCHMC）和哥伦比亚大学医学中心（CUMC）为中心的项目是由Wendy Chung MD博士（CUMC），Paul Kingma MD PhD（CCHMC），Yufeng Shen PhD（CUMC）领导 Wells PhD（CCHMC）和Aaron Zorn PhD（联系PI; CCHMC）。我们的计划有3个将链接在一起的项目综合基因组学核心。项目1：TED患者的全面表型和遗传评估。项目2：定义动物模型中TED的发育机制。项目3：在人类PSC衍生的胚胎组织中对EA进行建模。

项目成果

期刊论文数量（20）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Developmental basis of trachea-esophageal birth defects.

DOI：
10.1016/j.ydbio.2021.05.015
发表时间：
2021-09
期刊：
Developmental biology
影响因子：
2.7
作者：
Edwards NA;Shacham-Silverberg V;Weitz L;Kingma PS;Shen Y;Wells JM;Chung WK;Zorn AM
通讯作者：
Zorn AM

Discovering the Developmental Basis of Trachea-Esophageal Birth Defects: Evidence for Endosome-opathies.

发现气管食管出生缺陷的发育基础：内体疾病的证据。

DOI：
发表时间：
2022
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
0
作者：
Edwards,Nicole;Zhong,Guojie;Ahimaz,Priyanka;Kenny,Alan;Kingma,Paul;Wells,James;Shen,Yufeng;Chung,Wendy;Zorn,Aaron
通讯作者：
Zorn,Aaron

Enteroendocrine cell differentiation and function in the intestine.

DOI：
10.1097/med.0000000000000709
发表时间：
2022-04-01
期刊：
CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
影响因子：
3.2
作者：
Sanchez, J. Guillermo;Enriquez, Jacob R.;Wells, James M.
通讯作者：
Wells, James M.

Novel vectors for functional interrogation of Xenopus ORFeome coding sequences.

用于非洲爪蟾 ORFeome 编码序列功能询问的新型载体。

DOI：
10.1002/dvg.23329
发表时间：
2019
期刊：
Genesis (New York, N.Y. : 2000)
影响因子：
0
作者：
Sterner,ZacharyR;Rankin,ScottA;Wlizla,Marcin;Choi,JinyoungA;Luedeke,DavidM;Zorn,AaronM;Buchholz,DanielR
通讯作者：
Buchholz,DanielR

A Window into Your Gut: Biologically Inspired Engineering of Mini-gut Tubes In Vitro.

进入肠道的窗口：体外微型肠管的生物启发工程。