Leda Restrepo, Ph.D.

Research

In the MacFarlane lab, I will assess how changes in the activity of a gene regulator called Meg3 contributes to the risk of aortic aneurysms. The aorta, the branched vessel that carries blood from the heart, is particularly vulnerable to developing aneurysms, structural weaknesses that cause an artery to bulge and possibly rupture. Individuals with Loeys-Dietz syndrome (LDS), a hereditary disorder in which mutations disrupt a signaling pathway that regulates gene expression, harbor an increased risk of aortic aneurysms. In a preliminary study of a mouse model of LDS, I discovered that the activity of gene regulator Meg3 is altered in the smooth muscle cells that form the blood-vessel wall. Now, using an array of cutting-edge techniques in molecular and computational biology and single-cell RNA sequencing, I will examine the gene expression profiles in the aortas of LDS mice and patients and determine whether manipulating Meg3 activity can slow progression of the disease. My work could identify a novel therapeutic target for the life-threatening complications of this genetic disorder.