John J. Schwarz, PhD

Our research is directed at understanding how transcriptional regulation in endothelial cells controls activities of the endothelium such as modulating inflammation, thrombosis, and smooth muscle functions. The focus has been on MEF2 transcription factors. Their ability to activate transcription is increased by conditions that protect against atherosclerosis such as laminar shear stress and statin treatment. As such they are good candidates to understand how the endothelium protects against atherosclerosis and how transcriptional regulation can be used directly as a therapeutic target or indirectly to identify downstream targets that are more amenable for intervention. We found that one member of this family, Mef2c, in the endothelium inhibits smooth muscle migration into the intima, which is an important component of several vascular diseases. Specifically, endothelial-specific deletion of Mef2c causes migration of smooth muscle cells through fenestrations in the internal elastic lamina into the intima subjacent to the endothelium. We are currently investigating the mechanism through which Mef2c regulates either a repulsive or attractive signal from the endothelium to medial smooth muscle.