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Tag: Dennis Kyle

Streamlining sporozoite isolation from mosquitoes by leveraging the dynamics of migration to the salivary glands

Background: Sporozoites isolated from the salivary glands of Plasmodium-infected mosquitoes are a prerequisite for several basic and pre-clinical applications. Although salivary glands are pooled to maximize sporozoite recovery, insufficient yields pose logistical and analytical hurdles; thus, predicting yields prior to isolation would be valuable. Preceding oocyst densities in the midgut is an obvious candidate. However, it …

Single-cell RNA profiling of Plasmodium vivax-infected hepatocytes reveals parasite- and host- specific transcriptomic signatures and therapeutic targets

The resilience of Plasmodium vivax, the most widely-distributed malaria-causing parasite in humans, is attributed to its ability to produce dormant liver forms known as hypnozoites, which can activate weeks, months, or even years after an initial mosquito bite. The factors underlying hypnozoite formation and activation are poorly understood, as is the parasite's influence on the host …

Direct type I interferon signaling in hepatocytes controls malaria

Malaria is a devastating disease impacting over half of the world's population. Plasmodium parasites that cause malaria undergo obligatory development and replication in hepatocytes before infecting red blood cells and initiating clinical disease. While type I interferons (IFNs) are known to facilitate innate immune control to Plasmodium in the liver, how they do so has …

Increasing the knowledge base on brain-eating amoeba

Cassie Russell, a graduate student in the Department of Infectious Diseases, in her laboratory space. (Photo by Ian Bennett) Cassie Russell, a graduate student in the Department of Infectious Diseases, was an undergraduate when she first heard of Naegleria fowleri, also known as the brain-eating amoeba. While whole lectures in her parasitology course had been dedicated to …

Alkyne modified purines for assessment of activation of Plasmodium vivax hypnozoites and growth of pre-erythrocytic and erythrocytic stages in Plasmodium spp

Malaria is a major global health problem which predominantly afflicts developing countries. Although many antimalarial therapies are currently available, the protozoan parasite causing this disease, Plasmodium spp., continues to evade eradication efforts. One biological phenomenon hampering eradication efforts is the parasite's ability to arrest development, transform into a drug-insensitive form, and then resume growth post-therapy. …

Polychlorinated cyclopentenes from a marine derived Periconia sp. (strain G1144)

Studies on an organic extract of a marine fungus, Periconia sp. (strain G1144), led to the isolation of three halogenated cyclopentenes along with the known and recently reported rhytidhyester D; a series of spectrometric and spectroscopic techniques were used to elucidate these structures. Interestingly, two of these compounds represent tri-halogenated cyclopentene derivatives, which have been …

Metabolic, Pharmacokinetic, and Activity Profile of the Liver Stage Antimalarial (RC-12)

The catechol derivative RC-12 (WR 27653) (1) is one of the few non-8-aminoquinolines with good activity against hypnozoites in the gold-standard Plasmodium cynomolgi-rhesus monkey (Macaca mulatta) model, but in a small clinical trial, it had no efficacy against Plasmodium vivax hypnozoites. In an attempt to better understand the pharmacokinetic and pharmacodynamic profile of 1 and to identify potential active metabolites, …

Trainee Spotlight: Justine Shiau

Justine Shiau, an NIH T32 fellow in Dr. Dennis Kyle's laboratory, is originally from Taipei, Taiwan, and moved to the states after elementary school. She received her bachelor's degree in Biology from the Pennsylvania State University, where she became interested in disease transmission, disease ecology, and parasitology while working with Dr. Ashutosh Pathak. Upon graduation, …