Dr. Shelton is interested in understanding the molecular and genetic regulation of an essential blood vessel known as the ductus arteriosus (DA). This vessel shunts blood away from the underdeveloped lungs and directs it into the systemic circulation so that it can get oxygenated by the placenta during fetal life. However at birth, this vessel must constrict and seal itself off in order to establish proper blood flow to the lungs. In some cases, the ductus fails to close, a condition termed patent ductus arteriosus (PDA).
PDA is a significant cardiovascular disorder affecting 1 out of every 500-2000 term infants and 30-40 percent of the most critically ill premature neonates. Presently, the pharmacological therapies for PDA are limited, have adverse side effects, and are not specifically targeted to the DA. Therefore, one of the main focuses of the Shelton lab is to identify factors that set the DA apart from other vessels in the body in the hopes of developing novel DA-specific therapeutic regulators of vascular tone. Furthermore, she is interested in identifying adverse ductus-related side effects of pharmacological agents that are commonly administered to pregnant mothers or neonatal infants. For these studies, she uses a combination of primary cell culture models, cannulated vessel myography assays, and whole animal models to identify factors that constrict or relax the DA.
In addition, the Shelton lab is interested in how a person’s genes affect ductus function and response to medicine. She is currently working on human sequencing projects in order to identify genetic variations associated with PDA and resistance to pharmacological intervention.
Another interest of the Shelton lab is to identify non-vascular cell types that can be used to form new vasculature or repair injured vessels. Using in vivo mouse models and cell culture systems, she has demonstrated that mesothelium, a simple epithelium, has the potential to differentiate into vascular smooth muscle and endothelial cells that can be used for vessel repair. In collaboration with members of the department of bioengineering, she is using microfluidic bioreactors to investigate the effects of flow, cyclic stretching, and matrix composition on the ability of mesothelia to differentiate into vascular cells as well as other cell types including bone and cartilage.
Furthermore, she is interested in identifying genetic signatures for different populations of normal and pathological mesothelia. Understanding the nature of these cells will be useful in maximizing their therapeutic potential in tissue repair as well as provide new ways to limit their ability to form fibrotic lesions or tumors.