Many diseases such as atherosclerosis/ restenosis, cancer, stroke and diabetic retinopathies have known connections to vascular dysfunction exemplified by targeted disruptions in mural cell (MC) support of the vasculature. In diabetic retinopathy for instance, there is thought to be a drop-out of MCs surrounding blood vessels, making the remaining vasculature much more susceptible to micro-hemorrhages that are ultimately responsible for the blindness associated with the disorder. In atherosclerotic plaques, MCs are known to dedifferentiate to adopt a synthetic matrix producing phenotype that has been intimately connected to the progression of the disease. Despite the fact that there is a known phenotypic relationship between multiple diseases and MCs, there is an associated lack of mechanistic understanding of normal MC function to effectively develop specific therapeutics targeted at prevention and treatment of disorders.

Therefore, my labs long-term research interests focus on understanding MC biology during development and disease.  To build a functionally stable blood vessel that is able to withstand changes in shear stress and modulate vascular tone requires cooperation between two cell types: the endothelial cell (EC) and the mural cell (MC). MCs, a perivascular cell population that provides structural support to EC tube networks, can be split into subclasses, including smooth muscle cells and pericytes, based

on the anatomical location of the MC population within the vascular network. EC-MC interactions are known to be critical in stabilizing the vasculature by helping to withstand forces such as high shear stress/pulsatile pressure exerted on the vessels from blood flow coming out of the heart. MCs also promote barrier function at the blood brain barrier (BBB). Despite the critical nature of these cell-to-cell interactions, much more is known about genes regulating EC versus MC function.

 

Photo credit Dan Castranova

My lab uses zebrafish to study MC development and behavior. Zebrafish as a vertebrate model organism offer a number of advantages that make it an ideal system to study development of the vascular wall- including external fertilization, proper embryonic growth in the absence of functional vasculature or blood flow, optical clarity for longitudinal imaging, and genetic/experimental accessibility. The field remains largely uncharted giving us the unique opportunity to exploit newly developed tools to broaden the understanding of MC biology and the mechanisms regulating their behavior. Research in my laboratory will aid in the understanding of developmental processes regulating MC function and will in turn 1) provide a broader understanding of how the blood vessel wall is assembled, 2) define genetic pathways critical for MC function and 3) provide a platform to assess dysfunction in EC-MC interactions during disease.