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Category: publications

Cryogenically preserved RBCs support gametocytogenesis of Plasmodium falciparum in vitro and gametogenesis in mosquitoes

Donna Huber on December 6, 2018

Abstract Background: The malaria Eradication Research Agenda (malERA) has identified human-to-mosquito transmission of Plasmodium falciparum as a major target for eradication. The cornerstone for identifying and evaluating transmission in the laboratory is standard membrane feeding assays (SMFAs) where mature gametocytes of P. falciparum generated in vitro are offered to mosquitoes as part of a blood-meal. However, propagation of “infectious” …

Proximal Remote Sensing to Non-destructively Detect and Diagnose Physiological Responses by Host Insect Larvae to Parasitism

Donna Huber on December 4, 2018

As part of identifying and characterizing physiological responses and adaptations by insects, it is paramount to develop non-destructive techniques to monitor individual insects over time. Such techniques can be used to optimize the timing of when in-depth (i.e., destructive sampling of insect tissue) physiological or molecular analyses should be deployed. In this article, we present …

Anilinoquinoline based inhibitors of trypanosomatid proliferation

Donna Huber on November 26, 2018

Abstract We recently reported the medicinal chemistry re-optimization of a series of compounds derived from the human tyrosine kinase inhibitor, lapatinib, for activity against Plasmodium falciparum. From this same library of compounds, we now report potent compounds against Trypanosoma brucei brucei (which causes human African trypanosomiasis), T. cruzi (the pathogen that causes Chagas disease), and Leishmania spp. (which cause leishmaniasis). In addition, sub-micromolar …

CRISPR/Cas9 and glycomics tools for Toxoplasma glycobiology

Donna Huber on November 21, 2018

Abstract Infection with the protozoan parasite Toxoplasma gondii is a major health risk owing to birth defects, its chronic nature, ability to reactivate to cause blindness and encephalitis, and high prevalence in human populations. Unlike most eukaryotes, Toxoplasma propagates in intracellular parasitophorous vacuoles, but as for nearly all other eukaryotes, Toxoplasma glycosylates many cellular proteins and lipids and assembles …

Highly competent, non-exhausted CD8+ T cells continue to tightly control pathogen load throughout chronic Trypanosoma cruzi infection

Donna Huber on November 12, 2018

Abstract Trypanosoma cruzi infection is characterized by chronic parasitism of non-lymphoid tissues and is rarely eliminated despite potent adaptive immune responses. This failure to cure has frequently been attributed to a loss or impairment of anti-T. cruzi T cell responses over time, analogous to the T cell dysfunction described for other persistent infections. In this study, we have …

Genetic conservation of Cytauxzoon felis antigens and mRNA expression in the schizont life-stage

Donna Huber on November 6, 2018

Abstract Cytauxzoonosis is a highly fatal disease of domestic cats caused by the apicomplexan protozoan Cytauxzoon felis, which is most closely related to Theileria spp. The growing prevalence, high morbidity and mortality, and treatment cost of cytauxzoonosis emphasize the need for vaccine development. Traditional approaches for vaccine development, however, have been hindered by the inability to culture C. felis …

First evidence of polychaete intermediate hosts for Neospirorchis spp. marine turtle blood flukes (Trematoda: Spirorchiidae)

Donna Huber on October 25, 2018

Abstract Life cycles of spirorchiids that infect the vascular system of turtles are poorly understood. Few life cycles of these blood flukes have been elucidated and all intermediate hosts reported are gastropods (Mollusca), regardless of whether the definitive host is a freshwater or a marine turtle. During a recent survey of blood fluke larvae in …

Phenotypic screens reveal posaconazole as rapidly cidal combination partner for treatment of Primary Amoebic Meningoencephalitis

Donna Huber on October 24, 2018

Abstract Naegleria fowleri is the causative agent of primary amoebic meningoencephalitis (PAM), which is fatal in >97% of cases. In this study, we aimed to identify new, rapidly acting drugs to increase survival rates. We conducted phenotypic screens of libraries of Food and Drug Administration–approved compounds and the Medicines for Malaria Venture Pathogen Box and validated …

Phloroglucinols from the Roots of Garcinia dauphinensis and Their Antiproliferative and Antiplasmodial Activities

Donna Huber on October 24, 2018

  Abstract Garcinia dauphinensis is a previously uninvestigated endemic plant species of Madagascar. The new phloroglucinols dauphinols A–F and 3′-methylhyperjovoinol B (1–7) and six known phloroglucinols (8–13) together with tocotrienol 14 and the three triterpenoids 15–17 were isolated from an ethanolic extract of G. dauphinensis roots using various chromatographic techniques. The structures of the isolated compounds were elucidated by NMR, MS, optical …