Biochemistry, Biophysics, and Structural Biology Commons^™

Cardiac Modelling Techniques To Predict Future Heart Function And New Biomarkers In Acute Myocardial Infarction, Sergio C. H. Dempsey

Electronic Thesis and Dissertation Repository

Fundamental to treatment planning for patients that have suffered myocardial infarction are predictive biomarkers and risk factors. Important among these in terms of a patient’s treatment plan or prognosis are the contractility of the damaged myofibers, final infarct volume, and poor infarct healing rate. Proposed and developed in this thesis are techniques to predict these biomarkers and risk factors using cardiac biomechanical modelling. One of the developed techniques was a CT compatible shape optimization technique which can predict the contraction force of healthy, and stunned myofibers within 6.3% and the distribution of potentially necrotic myofibers within 10% accuracy. The second …

The Role Of Heat Shock Protein 90 In The Keap1/Nrf2 Mediated Oxidative-Stress Response, Zheng Song

Electronic Thesis and Dissertation Repository

Oxidative and proteotoxic stress are common hallmarks of Neurodegenerative diseases (NDs). Cellular proteostasis is maintained through Heat shock protein (Hsp) 90 and Stress-inducible protein 1 (STIP1) modulating the stability of their substrates (clients). Hsp90/heat shock factor (HSF)1 pathway activation attenuates proteotoxicity. Meanwhile, activating the Kelch-like ECH associated protein 1 (Keap1)/ nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway combats oxidative stress. Numerous studies attempted to individually manipulate the expression of Hsp90 or Nrf2 to treat NDs.

Novel interactions of Hsp90 with Nrf2 and Keap1 were discovered via yeast-2-hybrid screening (unpublished data). We analyzed their interactions through NMR spectroscopy, ITC, protein-binding assay, …