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

Abby S. Hill
2018 · W2919729457
dissertation OA: green CC0
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This MIT thesis presents an integrated experimental and computational framework for analyzing intercellular communication, applying the methodology to investigate mechanisms in endometriosis.

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This thesis investigates how intercellular communication shapes immune responses in health and disease, with a primary focus on the interactions between immune cells and endometrial tissue. The research utilizes both clinical samples and three-dimensional in vitro culture models to analyze dynamic processes involving endometrial stromal and epithelial cells alongside peripheral blood monocytes. Key findings highlight the critical role of macrophages in disease initiation and progression, specifically regarding cell survival, neovascularization, and neurogenesis within endometriotic lesions. This paper is centrally about endometriosis — specifically examining the immune-mediated mechanisms that drive lesion establishment and growth through integrated experimental and computational analyses.

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Abstract

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biological Engineering, 2018.
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Integrated experimental and computational analysis of intercellular communication with application to endometriosis Name 1080639262-MIT.pdf Description Full printable version Size 16.44 MB Format Adobe PDF Checksum (MD5) 6064eb49b22f3ae79e87c5a1ef749655 Author(s) Hill, Abby Shuman Advisor(s) Douglas A. Lauffenburger. Date Issued 2018 Publisher Massachusetts Institute of Technology 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. Description Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biological Engineering, 2018. Cataloged from PDF version of thesis. Includes bibliographical references (pages 143-162). Subjects Biological Engineering. MIT Department Massachusetts Institute of Technology. Department of Biological Engineering Terms of Use MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission. Persistent DSpace Link

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endometriosis

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