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| Abstract Title:
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| Modeling and analysis of the cellular response to ischemia: a systems biology approach
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| Graduate Student Presenter:
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Patrick W. Sheppard
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| Name of the Author(s) and Affiliation(s):
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Patrick W. Sheppard, Dept. of Mechanical Engineering, UC Santa Barbara; Mustafa Khammash, Dept. of Mechanical Engineering, UC Santa Barbara; Rona G. Giffard, Dept. of Anesthesia, Stanford University
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The ability of an organism to properly respond to injury or inhospitable conditions is essential for its survival. The response at the cellular level ultimately governs the biological response of the organism; however, this often involves several different types of interactions among many different species, forming a complicated network whose size and complexity obscure the basic underlying functions. The mammalian response to ischemia, i.e. reduced blood supply, serves as one example of such a response. Though it has been studied extensively, a detailed mechanistic understanding presently remains elusive thus making efforts to develop more effective therapies for stroke very difficult. Here, we present current work in which we combine theory and methods from computational sciences and engineering with experimental biology to advance understanding of the mammalian response to ischemia by analyzing the network at a systems level. A computational model composed of deterministic ODEs has been developed to simulate the dynamics of NF-kappaB mediated inflammation in microglia, and is currently being validated experimentally. In parallel, we are creating models describing apoptotic signaling that governs the programmed cell death response. The interactions of heat shock protein (Hsp70) with these pathways will be incorporated into the models and investigated, as Hsp70 overexpression has been observed to protect certain cells though the precise mechanism remains unclear. In addition several methods of systems analysis, including sensitivity analysis and a novel method for model reduction, are being utilized on this system to aid the fundamental understanding of the biological response.
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