TRACHEA-ESOPHAGEAL BIRTH DEFECTS

Esophageal atresia (EA) and tracheoesophageal fistula (TEF) commonly diagnosed birth defects, where the trachea and esophagus are not fully separated during fetal development, which is yet to be understood. Such defects occur in one out of every 3000 live births and can be corrected with surgery, with a survival rate of 90%.

The CLEAR Consortium goal is to better understand the genetic causes of trachea-esophageal birth defects, and to improve the health outcomes and quality of life of patients.

Program Overview

The CLEAR (Congenital Esophageal and Airway Defect Research) Consortium is a collaborative research program funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development focused on understanding birth defects (P01 HD093363). The goal of the CLEAR consortium is to discover the genetic and developmental causes of trachea-esophageal birth defects to enhance diagnosis, improve treatment, and explore the possibility of generating human stem cells that might ultimately be used in transplantation. By better understanding the genetic causes of trachea-esophageal birth defects, we aim to improve the diagnosis and treatment of these potentially life-threatening conditions.

As stated above, occurring in about one out of every 3000 live births, trachea-esophageal defects, such as Esophageal Atresia (EA) and Tracheoesophageal Fistula (TEF), occur when the fetal foregut fails to separate into distinct trachea and esophagus during early gestation. Trachea-esophageal defects may prevent proper breathing or feeding in newborn infants and are corrected with neonatal surgery. There is compelling evidence suggesting there is a genetic cause, but specific genetic mutations are only known for 12% of trachea-esophageal cases worldwide.

our approach

Our program uses three innovative, synergistic projects to reveal the genetic, molecular, and cellular bases of trachea-esophageal birth defects.

The first project is a comprehensive assessment of causative mutations (genotype) in trachea-esophageal defect patients using new MRI techniques to provide a detailed anatomic and functional analysis of these defects (phenotype). This clinical and genetic data is combined to establish a national trachea-esophageal defect registry.

The second project focuses on the molecular and cellular development of trachea-esophageal defects using animal models. Determining the disruptions in development of the trachea and esophagus in animal models will help to determine similar causes in human patients.

The third project focuses on stem cells to create human esophageal organoids in a dish. These novel stem-cell derived human foregut organoids will be used to investigate how mutations affect human esophageal and respiratory development. 

Learn more about our research projects.

Our Team

Led by Cincinnati Children’s Hospital and the Columbia University Medical Center, we are a highly-collaborative multidisciplinary team of clinicians, geneticists, surgeons, bioinformaticians, developmental biologists, and stem cell biologists.  The CLEAR Consortium includes over 15 collaborating hospitals and research institutions including the CARE network and the Midwest Pediatric Surgical Consortium.

Aaron Zorn, Ph.D. is the the Director of CuSTOM (Center for Organoid and Stem Cell Medicine) at Cincinnati Children’s Hospital Medical Center. He is also the Co-Director of the Digestive Health Center and the Co-Director of the Xenopus model organism database (Xenbase). His research lab focuses on using animal models, human stem cells, and cutting edge genomics to study birth defects. More info.

Paul Kingma, M.D., Ph.D. is board certified in Neonatology. He is the Co-Director of the Cincinnati Fetal Center and is Associate Professor of Pediatrics at Cincinnati Children’s Hospital Medical Center. He oversees patient databases, and basic and clinical research studies to improve the diagnosis and treatment of infancies with congenital anomalies. More info.

Wendy Chung, M.D., Ph.D. is the Director of the DISCOVER and TREATMENT programs at Columbia University. She has over twenty years of experience in genetics and has conducted genetic research on congenital heart disease, congenital diaphragmatic hernias, pulmonary hypertension, cardiomyopathy, autism, spinal muscular atrophy, diabetes, obesity, and breast cancer. She leads a number multicenter genetic studies. More info.

James Wells, Ph.D. is the Director of the Pluripotent Stem Cell Facility, Director for Basic Research in the Division of Endocrinology, and Chief Scientific Officer of CuSTOM (Center for Organoid and Stem Cell Medicine) at Cincinnati Children’s Hospital Medical Center. He is a pioneer in using human pluripotent stem cells to study gastrointestinal development and disease. His group has developed a novel human esophageal organoid system that will be used to investigate esophageal atresia. More info.

Yufeng Shen, Ph.D. is the Associate Director of the Genome Center at Columbia University. He led the analysis of the first personal genome sequenced by next-generation sequencing (NGS) technology, developed computational methods to detect genetic variants, including single nucleotide variants and copy number variants from NGS data. His group uses integrative genomic approaches to unravel the genetics of developmental diseases, including structural birth defects such as congenital heart disease and congenital diaphragmatic hernia, which both have shared genetic etiology with trachea-esophageal birth defects. More info.

Lead organizations

Collaborating institutions

Led by Cincinnati Children’s Hospital and Columbia University Medical Center, the CLEAR consortium (P01 HD093363) collaborates with institutions from the CARE Network and the Midwest Pediatric Surgery Consortium, including organizations nationally and globally:

• Cairo University Hospital

• Children’s Hospital & Medical Center - Omaha, Kansas

• CHU Sainte-Justine (Montreal, Canada)

• Johns Hopkins All Children’s Hospital

• Oregon Health and Science University - Doernbecher Children’s Hospital

• Seattle Children’s Hospital

• University of Texas Southwest - Children’s Medical Center of Dallas

Become a Participating Organization

Clinicians or scientists treating esophageal atresia/tracheoesophageal fistula patients, or investigating the cause of these conditions, are encouraged to join the CLEAR consortium. Please contact us at info@clearconsortium.org for more information.