Arsenic and Olfactomedin-1 Regulation of Epithelial to Mesenchymal Cell Transition (EMT) in Heart Valve Development

Abstract

This dissertation centers on the study of epithelial to mesenchymal cell transition (EMT) in the heart model of valve development. EMT is a process used by specific cells to invade adjacent matrix in order to differentiate into a three-dimensional structure. The first section of the project includes a study on the effects of inorganic arsenic on EMT and therefore the environmental concerns produced by deleterious effects on EMT. The second section focuses on the discovery of an intrinsic regulator of EMT, olfactomedin-1 (OLFM1). The discovery of a novel regulator of EMT in the atrioventricular canal is interesting, by itself, as it allows us to better understand the intrinsic molecular regulation of EMT in valve formation of the heart. The activity of this protein, as a regulator of cell invasion, identifies an important checkpoint in EMT. Because OFLM1 is conserved across many species, including humans, it may be a common or shared regulator of all types of EMT including cancer. Therefore, OLFM1 represents a promising new target for an anti-cancer agent as well as a potential clinical inducer of EMT to repair congenital heart disease that include valve defects.