BME PhD Prospectus Defense - RJ Seager

  • Starts: 1:30 pm on Tuesday, November 28, 2017
Title: “A Creature of Many Faces: Mechanical Regulation of TGF-β Signaling in the Tumor Microenvironment” Committee: Prof. Muhammad Zaman, BME (Advisor, Chair) Prof. Mary Dunlop, BME Prof. Mo Khalil, BME Prof. Roger Kamm, MIT Biological Engineering Abstract: A tumor is not a homogenous mass of cancer cells, but is in fact a diverse collection of various cell types, structures, signaling molecules, and environmental factors—all of which interact and contribute to tumor behavior. Cytokines are a broad class of signaling molecules involved in this intratumoral communication. One cytokine signaling pathway, transforming growth factor-β (TGF-β), controls a wide array of cellular processes including migration, metabolism, other cytokine signaling, and the epithelial-mesenchymal transition (EMT). This broad control allows it to act as both a tumor promoter and a tumor suppressor, though the mechanism by which it switches between these signaling programs is not entirely clear. The TGF-β pathway also interacts with mechanosensitive signaling pathways, making it sensitive to mechanical environmental features and forces. Thus, we posit that the mechanical tumor microenvironment influences whether TGF-β signaling acts as a tumor promoter or suppressor. Through mathematical modeling and experimental probing of these networks in cancer cells, we will analyze how changes in the mechanical environment affect TGF-β signaling, and how those signaling changes affect downstream cancer cell processes. Then, we will consider how these processes, when changed together, constitute tumor promotion or suppression, and endeavor to characterize and control this regulation. Through these efforts, we intend to broaden the accepted understanding of how mechanical regulation of intracellular signaling regulates metastatic behavior.
44 Cummington Mall, room 203

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