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Antibiotic Drug Discovery Targeting Bacterial Metabolism, Miranda J. Wallace
Antibiotic Drug Discovery Targeting Bacterial Metabolism, Miranda J. Wallace
Theses and Dissertations (ETD)
Over the last century, the use of antibiotics has enabled many advances in modern medicine, making life as we know it possible. In recent years, however, emerging bacterial resistance to virtually all major antibiotic classes has resulted in a worldwide increase in morbidity, mortality, and financial burden associated with drug resistant infections. The antimicrobial resistance crisis presents an urgent need for new antimicrobials with distinct mechanisms of action from existing drugs. The current pharmaceutical pipeline of new antibiotics is limited due to three obstacles: a lack of understanding of resistance mechanisms, a dearth of novel mechanisms of action among new …
Regulation Of Cyp3a5 In Pancreatic Ductal Adenocarcinoma, Jessica D. Hoyer
Regulation Of Cyp3a5 In Pancreatic Ductal Adenocarcinoma, Jessica D. Hoyer
Theses and Dissertations (ETD)
CYP3A5 is a drug metabolism enzyme that is polymorphically expressed in normal tissues and expressed in high amounts in some cancers, including pancreatic ductal adenocarcinoma (PDAC). There have been several published studies regarding CYP3A5 regulators, but there is still much to be discovered concerning CYP3A5 regulation in cancer. To further understand the regulation of CYP3A5, a high-throughput screen was performed in the AsPC-1 PDAC cell line. This screen employed small interfering RNA (siRNA) targeting transcription factors and chromatin-associated proteins. We identified siRNA that decreased CYP3A5 mRNA and protein levels in AsPC-1 cells and probed into the potential mechanisms. Taken together, …
An Investigation Into Clinically Relevant Determinants Of Azole Resistance In Candida Albicans, Andrew T. Nishimoto
An Investigation Into Clinically Relevant Determinants Of Azole Resistance In Candida Albicans, Andrew T. Nishimoto
Theses and Dissertations (ETD)
"Candida albicans is a commensal organism commonly colonizing the human gut and skin. As an opportunistic pathogen, it can cause persistent and serious infections in individuals with compromised immune systems, including the very young and elderly. Moreover, C. albicans can cause a wide spectrum of diseases ranging from superficial mucosal infections to life-threatening invasions of the organs and bloodstream. Candida species are the most common cause of invasive fungal disease, which is associated with high mortality and imposes a heavy toll on the healthcare system. Over the last 30 years, the azole antifungals have been a mainstay of antifungal therapy, …