Date of Award

Spring 5-15-2018

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Degree Name

Doctor of Philosophy (PhD)

Degree Type



Despite considerable effort to develop neuro and cardioprotective drugs there remains no treatment other than restoration of blood flow to treat hypoxic/ischemic injuries such as strokes and myocardial infarctions. This implies that our understanding of the basic mechanisms behind hypoxic injury is lacking. Recent studies have identified protein homeostatic (proteostatic) disruptions as playing a role in hypoxic injury. Yet, most of these studies have focused on cytoplasmic or endoplasmic reticulum (ER) proteostasis, with little attention to possible contributions of mitochondrial proteostasis. In order to address this gap in our knowledge I have performed experiments to determine if mitochondrial proteostasis is disrupted by hypoxia and if activators of mitochondrial proteostatic mechanisms such as the mitochondrial unfolded protein response (mtUPR) can protect against hypoxic injury. In order to begin to identify the mechanisms of proteostatic disruption following hypoxia I have identified mitochondrial proteins prone to aggregation following hypoxia and identified a number of other physiologic stressors that lead to mitochondrial proteostatic disruptions. Additionally I have conducted a small molecule screen to identify novel activators of the mtUPR.


English (en)

Chair and Committee

C. Michael Crowder

Committee Members

Aaron DiAntonio, Abhinav Diwan, S. Kerry Kornfeld, Michael Nonet,


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