Our lab is interested in the fundamentals of blood vessel formation and smooth muscle differentiation. We strive to understand how endothelial and smooth muscle cells communicate to create the vascular landscape that carries blood throughout our bodies. The experimental focus is on signaling mechanisms that occur between and within cells. The lab utilizes state-of-the-art molecular, cellular and genetic strategies to investigate these mechanisms. Signals emanating from one vascular cell type impinge on others causing precise changes in gene expression. Our goal is to link individual signals with the gene expression patterns that are ultimately responsible for the molecular and morphogenic changes associated with formation and maturation of blood vessels. We are always looking for enthusiastic, dedicated individuals that think hard work is fun and science is cool.
Examples of our Research
Blood Vessel Formation
To study blood vessel formation we employ a three-dimensional co-culture system. Endothelial cells and mural cells (smooth muscle, pericytes, or fibroblasts) are cultured together and blood vessels form in a collagen matrix. This in vitro assay allows us to manipulate the cells and perform molecular characterizations of the genes and proteins that are expressed in these vessels. We use this assay to define pathways that are involved in the communication of different vascular cell types.
Smooth Muscle Cells
Smooth muscle cells are grown in culture to examine how they undergo differentiation in defined conditions. Cells can be molecularly manipulated using chemicals, or by utilizing viral overexpression of cDNAs or siRNA knockdown strategies. Phenotypic examination can be performed by immunostaining for different proteins (shown in red and cyan) or by molecular analysis using Western blot and quantitative PCR. Cell adhesion and migration assays may also be performed.
Vessels in a mouse embryo are studied to determine how specific genes affect vascular development. Genetically modified mice allow us to test the role of individual genes on certain phases of blood vessel development. The vessels can be highlighted with transgenic markers (shown in blue) to visualize smooth muscle cells or endothelial cells.
Blood vessels within a mouse are studied for their molecular composition. Here, an arteriole from a mouse retina is stained to detect endothelial cells (red) and smooth muscle cells (green) to demonstrate the close association of these two cell types within the vasculature.
The lab uses various molecular and cellular methods to study phenotypic modulation: an event in which smooth muscle cells transition between phenotypes, usually within pathological blood vessels. Understanding the signaling events that regulate this process is our primary goal.
Our lab is currently investigating the role of microRNA miR-145 in vascular development and fibrosis. Using mouse models of fibrosis, we are defining mechanisms of cellular regulation.