Research & Projects

The disease mechanisms responsible for causing esophageal atresia (EA) and trachea-esophageal fistulas (TEF), common congenital anomalies of the trachea and esophagus, are poorly understood. Through our collaborative research program, the CLEAR consortium, we have discovered new genetic variants in patients born with EA/TEF. A major challenge is to efficiently test if these genetic differences cause disease.

To approach this challenge, we use research animal models including Xenopus (African clawed frog) and mice. Xenopus and mice have all of the same organs as humans, including a trachea and esophagus, and their organ development is similar, making them excellent models to study human development and disease.

During my postdoc I investigated the cell and developmental biology underlying normal and disrupted trachea-esophageal development:

Rapid, efficient testing of genetic variants in Xenopus

We use the latest CRISPR-Cas9 gene editing technologies to quickly generate gene-edited Xenopus and test if disrupting the orthologous gene discovered in human patients disrupts trachea-esophageal development in the frog embryo. See our published work here.

Discovering conserved cell biology of endosome trafficking during trachea-esophageal separation

From our human genetics studies we discovered that many patients have genetic variants in proteins involved in endosome trafficking pathways, a pathway all cells use to move proteins to different cellular domains and change the composition of their plasma membrane. How would disruptions to this ubiquitous pathway result in such a specific disruption in organ development? We found that endosomes transport polarity proteins to the right place at the right time to keep the trachea and esophagus cells organized during complex tissue fusion and tissue separation events. Read the preprint of our findings here.