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Pediatric Surgery
Computational Embryology
As pediatric surgeons, many of the illnesses that we treat are the result of abnormalities in embryonic or fetal growth and development. We use the methods of modern medicine to correct or improve these congenital conditions. But concomitant with this clinical activity is the hope that a better understanding of the mechanisms that guide embryonic development will allow us to intervene at these very early stages to prevent or ameliorate some of these conditions.
We strive to understand embryonic development at its most basic, mechanistic levels. To do so we perform computer simulation modeling of early embryonic systems, an approach we term computational embryology. We aim to reconstruct the instruction sets and interactions which guide embryonic cells. We examine both normal development and errors of development.
As an example, congenital diaphragmatic hernia is an anomaly that has been a clinical focus of our Division of Pediatric Surgery for many years. The defining physical abnormality is a failure of the diaphragm (the muscle layer between the chest and abdominal cavities) to form completely. As a result, rather than a solid sheet, a variable size hole occurs in a characteristic location. We have studied the process by which cell growth and division can form a solid tissue sheet and how errors in this process can generate defects like those seen in diaphragmatic hernia. To do so we devised a novel modeling strategy whereby our simulations combine experimental data directly with computer generated cells.
Development of the diaphragm occurs in the human embryo at about eight weeks after conception. From the perspective of a nine-month gestation this might seem to be a very early event. But in terms of embryonic development it is actually quite late. The most fundamental features of the embryo are laid down in the first few weeks after conception. A major focus of our work is to understand how this basic foundation of embryonic development is created. To do so we are modeling the very early embryo.
By applying methods of computational embryology we hope to help unravel the mechanisms by which a fertilized human egg develops into a healthy baby, how errors can occur in this vastly complex process, and how we may be able to better treat or prevent congenital anomalies in the future.
Lawrence Bodenstein, MD, PhDContact
- Pediatric Research - Computational Embryology
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