Integrated experimental and computational analysis of intercellular communication with application to endometriosis

Abstract

Cell-cell communication is critically important to the function of the immune system, allowing a systems-level determination of the appropriate type of immune response to a perturbation. The immune system has at its disposal multiple types of responses, some beneficial and others harmful, all of which require coordination among immune cells and between the immune system and non-immune tissue cells. In this thesis, we have explored the use of multiple experimental and computational methods to understand how intercellular communication shapes the immune response in health and disease. Applications of this work are primarily focused on endometriosis, a disease characterized by the presence of endometrial glands and stroma located outside of the uterus. Disease initiation (cell survival) and progression (including neovascularization and neurogenesis) are thought to depend on interactions with the immune system, particularly macrophages. We have investigated these interactions on several levels, using both clinical samples and 3D in vitro culture models. The model systems used here include endometrial stromal and epithelial cells as well as peripheral blood monocytes with which to study dynamic processes within either the eutopic endometrium or the endometriotic lesion environment.