Dr. George uses mathematical and computational models to study biological processes including cell movement, soft tissue biomechanics, biological fluid transport, and its influence on lung morphogenesis, growth and development. She is fascinated by the complexity of the human body and would like to understand how the body controls the positioning and development of different tissues and organs.
Her current research focuses on identifying the mechanisms that play key roles in embryonic lung branching. The human lung is made up of about 5 million branches, which is formed by 23 successive branch generations and is crucial for respiration. Lung branching is a complex process, an analysis of the mouse bronchial tree has shown that the tree is generated by three geometrically simple local modes of branching namely domain branching (where daughter branches form around the circumference of parent branches), planar bifurcation (tip divisions of parent branches that occur along the anterior-posterior position of the parent branch) and orthogonal bifurcation (with ~90 degrees rotation in the bifurcation plane between parent and daughter branches).
It is unknown how the patterning information that is required to generate the millions of lung branches is genetically encoded. It is also not understood how the size, shape and location of each lung branch is specified. Dr. George’s research on embryonic lung branching focuses on unraveling the mechanism that generates the different modes of lung branching. She proposes that the different modes of branching are not determined wholly by genetic encoding but are influenced greatly by the physical structure of the pleural surface of the lung. Her past research has identified the role of fluid flow in lung branching. New results from her research have identified the role of lung geometry on the positioning of the planar and orthogonal branching in the bronchial tree during lung development.
As the fetus develops, sometimes the diaphragm does not develop properly which may result in the development of a hole or even be absent. This is called congenital diaphragmatic hernia (CDH) and it affects approximately 1 in 3000 live births. CDH usually limits the development and growth of the lung. In humans, fetal tracheal occlusion is used as a last resort in the treatment of underdeveloped lungs caused by fetal CDH. Fetal tracheal occlusion is a reversible procedure in which a tiny inflated balloon is inserted into the fetus to plug the trachea. This procedure allows the fetus’ lungs to grow. After several weeks, the balloon is removed while the pregnancy continues. Mortality is greater than 90% in fetuses with severe CDH. The success rate for CDH fetuses subjected to fetal tracheal occlusion is less than 50%. The mechanism by which tracheal occlusion accelerates lung branching is not fully understood.
Her goal is to understand how fluid flow and bio-mechanical forces regulate lung branching morphogenesis. This would provide invaluable tools/knowledge that would enhance the implementation of new therapeutic strategies to combat prenatal lung hypoplasia.