This Faculty Early Career Development (CAREER) grant will study endothelial cells. Specifically, this work will measure how these cells respond to mechanical stimuli generated by ultrasound, and will also investigate if ultrasound can be strategically used to promote normal cell functions. Endothelial cells form the inner lining of arteries and are constantly exposed to mechanical stimuli from blood flow and pressure. Blood flow has been shown to be a key regulator of normal endothelial cell functions. The more turbulent the blood flow, the more function is impaired. When the function of these cells is impaired, the artery is primed to develop diseases including heart disease. The knowledge gained about endothelial cells and their response to specific uses of ultrasound may someday lead to a novel therapy to prevent, or even reverse, diseases. This award will also enable the development of new learning modules that seek to excite students, particularly from underrepresented groups, about engineering. K-12, undergraduate, and graduate students will learn how engineering concepts can be used to solve problems in medicine. Dissemination of these learning modules at the K-12 level will be facilitated by collaborations with the Engineering Ambassadors Network and Nebraska 4-H. Together, the research and education goals of this award will advance our understanding of endothelial cell behavior and create a scientific learning and mentoring environment led by the Principal Investigator that will continue to broaden participation after the award has ended.
The research goal of this award is to characterize mechanosensitive signaling in endothelial cells exposed to low intensity pulsed ultrasound over a range of acoustic pressures and frequencies. This will be accomplished through two objectives, (1) identification of the ultrasound parameters that induce endothelial cell expression of the same mechanosensitive genes as laminar flow, and (2) assessment of the efficacy of ultrasound to rescue a normal phenotype in endothelial cells exposed to inflammatory stimuli. These objectives will be performed in vitro with arterial endothelial cell monolayers and gene expression will be evaluated from a panel of markers known to be sensitive to laminar flow. This research will create new knowledge on endothelial cell mechanobiology that introduces a shift in focus from physiologic mechanical stimuli to that generated through an artificial mechanism, which could underlie the development of new avenues of translation to the clinic.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.