Honors & Awards
Graduate Research Fellowship, National Science Foundation (2014-2017)
Education & Certifications
B.A., Reed College, Biochemistry & Molecular Biology (2011)
Development of resistance against current antimalarial drugs necessitates the search for novel drugs that interact with different targets and have distinct mechanisms of action. Malaria parasites depend upon high levels of glucose uptake followed by inefficient metabolic utilization via the glycolytic pathway, and the Plasmodium falciparum hexose transporter PfHT, which mediates uptake of glucose, has thus been recognized as a promising drug target. This transporter is highly divergent from mammalian hexose transporters, and it appears to be a permease that is essential for parasite viability in intra-erythrocytic, mosquito, and liver stages of the parasite life cycle. An assay was developed that is appropriate for high throughput screening against PfHT based upon heterologous expression of PfHT in Leishmania mexicana parasites that are null mutants for their endogenous hexose transporters. Screening of two focused libraries of antimalarial compounds identified two such compounds that are high potency selective inhibitors of PfHT compared to human GLUT1. Additionally, 7 other compounds were identified that are lower potency and lower specificity PfHT inhibitors but might nonetheless serve as starting points for identification of analogs with more selective properties. These results further support the potential of PfHT as a novel drug target.
View details for DOI 10.1371/journal.pone.0123598
View details for PubMedID 25894322
Dyotropic rearrangements of fused, tricyclic ?-lactones are described that proceed via unprecedented stereospecific, 1,2-acyl migrations delivering bridged, spiro-?-butyrolactones. A unique example of this dyotropic process involves a fused bis-lactone possessing both ?- and ?-lactone moieties which enabled rapid access to the core structures of curcumanolide A and curcumalactone. Our current mechanistic understanding of the latter dyotropic process, based on computational studies, is also described. Other key transformations in the described divergent syntheses of (-)-curcumanolide A and (-)-curcumalactone from a common intermediate (11 and 12 steps from 2-methyl-1,3-cyclopentanedione, respectively), include a catalytic, asymmetric nucleophile (Lewis base)-catalyzed aldol-lactonization (NCAL) leading to a tricyclic ?-lactone, a Baeyer-Villiger oxidation in the presence of a ?-lactone, and highly facial-selective and stereocomplementary reductions of an intermediate spirocyclic enoate. The described dyotropic rearrangements significantly alter the topology of the starting tricyclic ?-lactone, providing access to complex spirocyclic cyclopentyl-?-lactones and bis-?-lactones in a single synthetic operation.
View details for DOI 10.1021/ja303414a
View details for Web of Science ID 000307487200039
View details for PubMedID 22853802