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Theses/Dissertations

2012

Open Access Dissertations

Cancer

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Allosteric Regulation Of Caspase-6 Proteolytic Activity, Elih M. Velazquez-Delgado Sep 2012

Allosteric Regulation Of Caspase-6 Proteolytic Activity, Elih M. Velazquez-Delgado

Open Access Dissertations

Caspases are cysteine proteases best known for their controlling roles in apoptosis and inflammation. Caspase-6 has recently been shown to play a key role in the cleavage of neurodegenerative substrates that causes Huntington and Alzheimer's Disease, heightening interest in caspase-6 and making it a drug target. All thirteen human caspases have related specificities for binding and cleaving substrate, so achieving caspase-specific regulation at the active site has been extremely challenging if not impossible. We have determined the structures of four unliganded forms of caspase-6, which attain a novel helical structure not observed in any other caspases. In this conformation, rotation …


Risk Factors For Future Cardiac Diseases In Childhood Cancer Survivors, David C. Landy Apr 2012

Risk Factors For Future Cardiac Diseases In Childhood Cancer Survivors, David C. Landy

Open Access Dissertations

Background: With 12,000 children diagnosed with cancer annually in the United States and survival rates approaching 80%, the long-term health of childhood cancer survivors is an increasingly important concern. This is especially true given that over 70% of survivors develop a chronic health condition by 30 years after their original diagnosis. Cardiovascular diseases (CVD) are the most common non-cancer related complications. Although some risk factors for therapy-induced cardiovascular damage have been identified, their influence on longitudinal CVD risk is not well described, and therefore, their clinical utility is limited. While guidelines exist for protecting the long-term cardiovascular health of survivors, …