Astrof Research

Contact

Name: Sophie Astrof, PhD
Position: Associate Professor

1020 Locust Street
543F JAH
Philadelphia, PA 19107

Telephone: 215-955-9982
Heart

Congenital heart disease is among the most prevalent forms of human birth defects. Our lab seeks to understand the mechanisms regulating the development of the cardiovascular system and the processes that go awry in congenital heart disease.  We are using genetics, cell biology and 3-dimensional imaging to uncover signaling pathways mediating intercellular communications between distinct populations of progenitors regulating morphogenesis of the heart and associated blood vessels.

Research Projects

Neural crest cell-autonomous functions of fibronectin in cardiovascular development

We discovered that fibronectin specifically synthesized by the neural crest plays a requisite role in the regulation of mammalian cardiovascular development and morphogenesis of the aortic arch arteries. In particular, we found that neural crest-synthesized fibronectin facilitates Notch signaling and the differentiation of neural crest cells into vascular smooth muscle cells around pharyngeal arch arteries. Current studies in the lab are focused on understanding the mechanisms of this regulation.

Roles of fibronectin & integrin a5 in the formation of the pharyngeal arch arteries

We found that the expression of fibronectin and integrin a5 in pharyngeal mesoderm, endoderm and surface ectoderm regulates the formation of the pharyngeal arch arteries. We are using temporal lineage mapping analysis, whole-mount immunofluorescence and 3D imaging to understand the mechanisms, whereby cell-extracellular interactions regulate blood vessel morphogenesis.

Stage-dependent development of the pharyngeal arch arteries

Mechanisms regulating the formation of the pharyngeal arch arteries from endothelial progenitors

Studies under this project will identify progenitors that give rise to the endothelium of the pharyngeal arch arteries, and the pathways regulating arch artery development. This will help us understand mechanisms and etiology of congenital heart disease, including DiGeorge syndrome, caused by the most common chromosomal abnormality in humans.