Integrating biomechanical and biochemical signaling in lacrimal gland development

Columbia University Health Sciences, New York NY

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Abstract

PROJECT SUMMARY The long-term objective of this project is to investigate the signaling mechanisms governing lacrimal gland development, which has important implications for understanding the etiology of diseased lacrimal glands in humans. The lacrimal gland, a complex organ comprising acinar, myoepithelial, and duct cells, presents a unique model for studying cellular interactions. Despite its importance, the signaling pathways among these cell types remain poorly understood. Central to our investigation is the hypothesis that adherens junctions regulate the Hippo-Yap pathway, which in turn modulates Notch signaling during lacrimal gland development. Using conditional mutant mouse models, we will examine the role of cadherins in restraining Yap activity and promoting acinar cell genesis. We will employ multiomic analysis to elucidate the genetic and epigenetic regulatory networks controlled by Yap in the lacrimal gland. Lastly, we will investigate the intersection between Yap and Notch signaling pathways in acinar cell maturation. By deciphering the intricate interplay of biomechanical and biochemical signals, this project holds the potential to unveil novel therapeutic targets for human lacrimal gland dysfunction and dry eye disease. This could lead to the development of innovative treatments, offering significant relief to millions of patients.