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The Washington Research Foundation Fellowship

Elizabeth Stanley, Microbiology, 2011-12 WRFF

Liz Stanley photoI began working in Mark Majesky’s lab at Seattle Children’s during my sophomore year of college, and since then research has been an integral part of my studies. The Majesky lab focuses on the genetics and development of the cardiovascular system. In particular my work relates to a congenital heart defect called coarctation of the aorta, which entails a distinct narrowing of the vessel and requires surgical repair. I have been working on this particular project for just over a year now, and am excited to move beyond a preliminary stage with support from the WRF.

My experience with undergraduate research has increased the enthusiasm I already had for science, and has motivated me to move ahead with research as a career. I look forward to applying to graduate school while seeing what I can accomplish during my time in the coming year with support from the WRF.

Mentor: Mark Majesky, Pediatrics, Pathology

Project Title: Characterization of the Ductus-Aorta Boundary by Differential Expression of Chemorepulsive Ligands and Receptors

Abstract: Congenital heart defects are the most common form of birth defect, affecting about one out of every 100 newborns in the US. Ten percent of these afflicted newborns will experience a narrowing of their aorta, formally called coarctation of the aorta. Coarctation can result in extreme hypoxia in tissues that do not receive sufficient blood supply, and can eventually lead to congestive heart failure; surgical repair is required for the infant to regain normal circulation. The etiology of coarctation has been linked in many cases to migration of cells from the ductus arteriosus into the aorta. The ductus arteriosus is a fetal vessel that must close at birth, and does so by constriction of its smooth muscle cells until its lumen is occluded. If these contractile cells migrate into the aorta, they can constrict, narrowing the aortic lumen. Preliminary data from experiments on the region where the ductus inserts into the aorta show a differential expression of chemorepulsive signaling proteins from the Slit and Robo families in ductal versus aortic tissue, suggesting that a distinct tissue boundary forms in this region. This is supported by previous studies in lineage mapping, which demonstrated a distinct somite-neural crest smooth muscle lineage boundary in the aortic arch. In order to elucidate the role that Slit and Robo proteins play in determining the ductus-aorta boundary, I use reverse transcription PCR and microarray analysis to examine the expression of Slit-Robo ligand and receptor proteins in perinatal ductal and aortic tissue. By comparing expression in normal samples with samples from patients with coarctation, more insight into the influence of Slit-Robo chemorepulsive signaling on boundary formation will be gained. Characterization of the ductus-aorta boundary by identification of differential ligand-receptor expression is critical to understanding the role that abnormal boundary formation plays in coarctation of the aorta.