Research
Congenital heart disease is among the most prevalent forms of human birth defects. Our lab seeks to understand 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 and extracellular matrix-mediated communications among progenitors giving rise to the cardiovascular system. Our goals are to uncover cellular, molecular, and genetic mechanisms underlying congenital heart disease.
Key Focus Areas
I. 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 regulating the cell-type-specific expression of fibronectin in the neural crest.
II. Roles of fibronectin and integrin a5 in the formation of the pharyngeal arch arteries. We found that the expression of fibronectin and integrin α5β1 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 the morphogenesis of the aortic arch arteries.
III. 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 the mechanisms and etiology of congenital heart disease, including 22q11 deletion syndrome (also known as DiGeorge syndrome), the most common congenital chromosomal abnormality in humans.
IV. Mechanisms regulating fibronectin matrix formation. We use CRISPR-mediated mutagenesis and single-molecule localization microscopy to study the mechanisms by which fibronectin assembles into extracellular matrix fibrils.