Dynamics of Cell Fate Decisions Mediated by the Interplay of Autophagy and Apoptosis in Cancer Cells:  Mathematical Modeling and Experimental Observations    

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dc.contributor.authorTavassoly, Imanen
dc.contributor.committeechairTyson, John J.en
dc.contributor.committeememberClarke, Roberten
dc.contributor.committeememberBaumann, William T.en
dc.contributor.committeememberLi, Liwuen
dc.contributor.committeememberFinkielstein, Carla V.en
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.date.accessioned2017-10-07T06:00:30Zen
dc.date.available2017-10-07T06:00:30Zen
dc.date.issued2013-08-21en
dc.description.abstractAutophagy is a conserved biological stress response in mammalian cells that is responsible for clearing damaged proteins and organelles from the cytoplasm and recycling their contents via the lysosomal pathway. In cases where the stress is not too severe, autophagy acts as a survival mechanism. In cases of severe stress, it may lead to programmed cell death. Autophagy is abnormally regulated in a wide-range of diseases, including cancer. To integrate the existing knowledge about this decision process into a rigorous, analytical framework, we built a mathematical model of cell fate decision mediated by autophagy. The model treats autophagy as a gradual response to stress that delays the initiation of apoptosis to give the cell an opportunity to survive. We show that our dynamical model is consistent with existing quantitative measurements of time courses of autophagic responses to cisplatin treatment. To understand the function of this response in cancer cells we have provided a systems biology experimental framework to study dynamical aspects of autophagy in single cancer cells using live-cell imaging and quantitative uorescence microscopy. This framework can provide new insights on function of autophagic response in cancer cells.en
dc.description.degreePh. D.en
dc.format.mediumETDen
dc.identifier.othervt_gsexam:1530en
dc.identifier.urihttp://hdl.handle.net/10919/79557en
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectApoptosisen
dc.subjectAutophagyen
dc.subjectCanceren
dc.subjectCell Deathen
dc.subjectDynamic Modelingen
dc.subjectLive Cell Imagingen
dc.subjectQuantitative Fluorescence Microscopyen
dc.subjectSingle-Cellen
dc.titleDynamics of Cell Fate Decisions Mediated by the Interplay of Autophagy and Apoptosis in Cancer Cells:  Mathematical Modeling and Experimental Observations    en
dc.typeDissertationen
thesis.degree.disciplineGenetics, Bioinformatics, and Computational Biologyen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePh. D.en

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