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Weiwei Yin - Ph.D. Defense

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Advisor: Dr. Eberhard O. Voit (Department of Biomedical Engineering, Gatech)
Dr. Melissa L. Kemp (Department of Biomedical Engineering, Gatech)
Dr. Manu O. Platt (Department of Biomedical Engineering, Gatech)
Dr. Hanjoong Jo (School of Medicine, Emory)
Dr. Kathy K. Griendling (School of Medicine, Emory)

NADPH oxidase 1 (Nox1) has been identified to play a key role for amplifying reactive oxygen species production in vascular system. In spite of the considerable amount of experimental studies that have been conducted in the field, the exploration of the underlying regulatory mechanisms of the Nox1 system in vascular cells is incomplete and unclear. Many open questions remain that have not been addressed, and it will be hard to answer them with purely experimental methods. Therefore, in order to improve our understanding, the objective of this dissertation is to investigate how Nox1 activity is differently and dynamically regulated by distinct extracellular stimuli in vascular system by using computational and modeling methods.

Two specific cell types, namely endothelial cells and vascular smooth muscle cells are used as “templates” to investigate distinct modes of regulation of Nox1 in different vascular cells. Furthermore, two distinct extracellular stimuli, namely mechanical shear stress and hormones like angiotensin II, are respectively treated as representative Nox1 activators in each cell. By using a diverse array of modeling methods and computer simulations, this research identifies different types of regulation and their distinct roles in the activation process of Nox1, reveal generic features of alternative disassembly mechanisms of Nox1, and predict the overall dynamic behavior of the Nox1 system. The studies and investigations combined together improve our current understanding of the Nox1 system in the vascular system and might help us to develop potential strategies for manipulation and controlling Nox1 activity in the future.

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  • Workflow Status:Published
  • Created By:Chris Ruffin
  • Created:06/04/2012
  • Modified By:Fletcher Moore
  • Modified:10/07/2016

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