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Dynamic Mechanisms Of Multidrug Resistance In Human Cancers And Gram Negative Pathogens, Lauren Ammerman

Biological Sciences Theses and Dissertations

This dissertation focuses upon dynamic agents of multidrug resistance (MDR). We used a combination of in silico and in vitro techniques to investigate two membrane transporters that confer MDR – P-glycoprotein, which confers MDR in human cancers, and MtrD, which confers MDR in Neisseria gonorrhoeae. Inhibitors targeting both proteins have tremendous potential for use as co-therapeutics in the treatment of multidrug resistant cancers, or of multidrug resistant infections. However, previously identified inhibitors of P-gp have failed clinical trials due to off-target effects and associated toxicities. Furthermore, the molecular mechanism of antibiotic transport by MtrD is poorly understood, and this dearth …