Apoptosis modulation in cancer cells

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Tumor necrosis factor alpha (TNFa), a pleiotropic cytokine capable of exhibiting pro-survival, apoptosis, or necrotic phenotypes, is implicated in several cancers. Understanding the underlying mechanism that governs a cell’s decision to apoptotic phenotypic response, a desired outcome, can help obtain insights on how signal flow to cell-death can be modulated. This leads to a question as to what intracellular interventional strategies could be employed to manipulate signal flow to cell-death state. The goal of this project is to develop a mechanistic model of underlying biochemical network to predict the in-house measured dynamics of levels of phosphorylated-proteins, such as MAPK cascades that control apoptotic response, in an ensemble of cancer cells exposed to TNFa. A combination of advanced state estimation approaches and systematic sensitivity analysis of the model will be used to decipher strategies for modulation of apoptotic response. This project will involve computations on MATLAB and other computing platforms.

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