Carmen M. Halabi, MD, PhD
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Washington University in St. Louis (WU)
Our lab’s overall focus is to understand how mutations in extracellular matrix genes lead to abnormal vascular development and disease. Similar to humans with cutis laxa caused by mutations in the extracellular matrix gene Fibulin-4; mice carrying mutations in Fibulin-4 develop aortic aneurysms and arterial tortuosity thought to be related to abnormal elastic fiber formation. Examination of the vasculature in this model showed surprising and previously unrecognized differences in the development of large conduit arteries versus small resistance arteries where elastic fibers of large conduit arteries were fragmented and disorganized, while those of small arteries muscular arteries were intact, suggesting that the process of elastic fiber assembly differs along the vascular tree. The aims of our lab are to understand the mechanisms by which mutations in Fibulin-4 lead to aneurysm development and to investigate differences in the development of small versus large arteries.