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The Levinson Emerging Scholars ProgramChristine Masuda - Neurobiology
Mentor: Prof. Peter Rabinovitch, Department of Pathology Project Title: Possible neuroprotective effects of mitochondrially-targeted catalase in the 3-NP model of acute oxidative stress Abstract: There is considerable evidence that oxidative stress, resulting from exogenous and endogenous free radicals, has a causal role in aging and age-related disease, in particular, neurodegenerative diseases. The mitochondria have been shown to be the foremost site of endogenous free radical production. To further investigate this, we will study a transgenic mouse that expresses human catalase (an antioxidant enzyme) that is targeted to the mitochondria. This transgenic mouse demonstrates a 20% increase in life span and decreases in age-related pathology in the heart and possibly skeletal muscle. While there is research underway focusing on heart and skeletal muscle, this project will specifically relate to the brain, which has not yet been examined. One model that can test the importance of mCAT expression in the brain is the 3-nitropropionic (3-NP) model of acute oxidative stress. 3-NP is an irreversible inhibitor of succinate dehydrogenase, complex II in the electron transport chain of the mitochondria. 3-NP has been used by other investigators to recapitulate the clinical features of Huntington’s Disease, another age-related neurodegenerative disorder. These investigators have demonstrated that 3-NP produces selective striatal lesions that are attributed to neurotoxic effects of oxidative damage. In this study, we will investigate the possible neuroprotective effects of the mCAT compared to WT in the 3-NP model. |
Christine’s interest in medical research began with a histology project in high school and has deepened throughout her undergraduate years. She was her high school valedictorian, and won a prestigious Washington Scholars award for tuition at any college or university in the state as a high school senior. Her ultimate goal is to become a physician-scientist, linking clinical medicine and basic biology. She states: “I want to practice medicine with the analytical skills learned from research and to conduct research with human faces behind my motivation.” Her mentor ranks her among the very best students he has taught, speaks highly of Christine’s talent for research, and the critical timing of this award: “I believe that Christine has reached a defining moment in her undergraduate training as she embarks on an increasingly independent trajectory.” Christine’s award will provide support for research supplies and conference travel.