A Mechanistic Exploration of Abnormal Angiogenesis in Single Ventricle Congenital Heart Disease: Discovering Novel Therapies

Students

College Wharton

Faculty

Cardiovascular Surgery

Project Summary

Children born with single-ventricle congenital heart disease require a multi-stage surgical procedure culminating in a total cavo-pulmonary connection (Fontan circulation) to survive. The second stage of this procedure is known as the Glenn circulation, and involves creating a connection between the superior vena cava and the right pulmonary artery – this allows deoxygenated blood to be passively routed to the lungs, decreasing stress on the single functioning ventricle. In some cases, the Glenn circulation may in fact be more durable than the full Fontan.
 
The goal of my project was to study one of the major complications of the Glenn circulation, which is the development of abnormal blood vessels known as pulmonary arteriovenous malformations (AVMs). These AVMs negatively affect the longevity of the Glenn circulation, and can result in cyanosis and even death if unaddressed. We analyzed blood samples taken from Glenn patients to characterize abnormalities in angiogenic signaling as well as in vitro angiogenesis in two cell lines: human umbilical vein endothelial cells and pediatric pulmonary microvascular endothelial cells.
 
During my time in lab this summer, I learned a great deal about research in translational medicine. Our lab operates on the boundary between Penn Medicine, the Hospital of the University of Pennsylvania, and the Children’s Hospital of Philadelphia – as a result, I was involved in everything from patient screening and recruitment, to collecting and processing blood samples, to then using those samples to run experiments in lab. Such a diverse set of experiences has fueled my own desire to pursue a career as a physician-scientist, since it’s truly inspirational to witness firsthand how our work on the benchtop could affect the quality of care for patients at HUP and CHOP in the future.
 
I look forward to continuing my work in this lab through the remainder of my time at Penn, and I thank my mentors in the lab for giving me this opportunity.