Date Degree Awarded

Fall 12-16-2016

Degree Type

Open Access Dissertation

Degree Name

PHD in Applied Life Sciences

First Thesis/Dissertation Advisor

Mikhail Martchenko

Second Thesis/Dissertation Advisor

Animesh Ray

Third Thesis/Dissertation Advisor

Ian M Phillips

Terms of Use & License Information

Terms of Use for work posted in Scholarship@Claremont.

Abstract

Drug resistance is a longstanding and still-increasing threat to the effective treatment of infectious diseases. Discovering drugs that target host proteins involved in pathogenicity is a strategy that could address this problem. Unfortunately, there are currently no FDA-approved infectious disease therapies that specifically target host proteins. Our goal is to develop a method to i) quickly discover new drugs for the treatment infectious diseases, ii) identify the specific host protein target of the drugs, iii) investigate the broad spectrum application of the drugs. To find these types of drugs, we employed a novel multiplex drug screening method in which we used disease pathway knowledge to more effectively screen a library of FDA-approved drugs. We utilized a cell-based survival assay to determine safety and efficacy and a biochemical-based assay to determine the host protein target of the drugs. This methodology led to the discovery of two FDA-approved drugs and their host protein targets. In addition, these drugs were shown to be safe and effective in animal models. These results suggest that our novel multiplex drug screening method can be used to address the drug resistance problem.

DOI

10.5642/kgitd/5

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