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| Name |
Phillips, Margaret A. |
| Location
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The University of Texas Southwestern Medical Center |
| Primary Field
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Animal, Nutritional and Applied Microbial Sciences |
| Secondary Field
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Microbial Biology |
 Election Citation
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Margaret A. Phillips studies the biochemistry of the protozoan pathogens that cause malaria and African sleeping sickness and identifies and exploits metabolic vulnerabilities to advance drug development.
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Research Interests
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The Phillips lab is interested in the biochemistry of the protozoan pathogens that cause malaria and African sleeping sickness, and on exploiting metabolic vulnerabilities for drug discovery. Her lab has focused on two main areas: 1) targeting the pyrimidine biosynthetic pathway for the treatment of malaria, and 2) studying polyamine metabolism and its regulation in Trypanosoma brucei (causative agent of sleeping sickness). In her malaria program, Phillips employed a high-throughput screen against malaria dihydroorotate dehydrogenase to identify potent and selective inhibitors of the enzyme. Subsequent structure-based lead optimization efforts by her lab and her collaborators lead to the identification of DSM265, which reached clinical development for treatment of malaria. In her trypanosome project, her lab characterized the polyamine biosynthetic pathway, where they explored the fundamental roles of the polyamine biosynthetic enzymes in the parasite, demonstrating that all enzymes in the pathway are essential. They uncovered novel regulatory mechanisms for two enzymes in the pathway, S-adenosylmethionine decarboxylase and deoxyhypusine synthase. Her lab showed that both enzymes require oligomerization with inactive paralogs (i.e., pseudoenzymes) for activity, revealing a trypanosomatid-specific form of enzyme regulation. Subsequent structural studies by her group identified the mechanism of pseudoenzyme activation for both enzymes.
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