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Category: publications

Spatiotemporal dynamics of signal dependent exocytosis and parasitophorous vacuolar membrane rupture during Plasmodium falciparum egress

  Malaria, caused by intracellular Plasmodium falciparum parasites, remains a major global health concern. These parasites reside and replicate within a vacuole in host red blood cells. Egress of daughter parasites out of the vacuolar and host membranes is tightly regulated via a complex mechanism. Prior studies have suggested that a cyclic-GMP driven calcium signaling …

Evolutionary remodeling of ubiquinone biosynthesis in Toxoplasma gondii reveals an essential bi-functional monooxygenase

Apicomplexan parasites like Toxoplasma gondii harbor a divergent mitochondrial proteome, much of which remains uncharacterized despite its essentiality for parasite survival. One such essential pathway is ubiquinone (UQ) biosynthesis. Here, we characterize the UQ synthesis machinery in T. gondii and show that conserved enzymes, TgCoq3 and TgCoq5, are essential for growth and mitochondrial function, and …

Identification of an Orally Efficacious Imidazo[4,5- c]pyridine-6-Carboxamide Antimalarial with a High Barrier to Resistance

Due to the emergence of resistance to both artemisinin derivatives, and their partner drugs, new antimalarials are urgently needed. Ideally, new orally active antimalarials would not only engage new targets but also demonstrate a high barrier to resistance selection, and the ability to kill both proliferating rings and growth-arrested rings resulting from artemisinin exposure. In …

Vaccine elicitation of HIV broadly neutralizing antibodies from genome-edited B cells in non-human primates and derived lymphoid organoids

HIV broadly neutralizing antibodies (bnAbs) are promising reagents for prevention and therapy of disease; however, their elicitation is constrained by genetic limitations of the human B cell antigen-receptor (BCR) repertoire. Precision genome-editing offers a potential solution by enabling bnAb genes to be programmed into the BCR repertoire as IgH-modified B cells. Such cells can be …

Glycosomal Phosphoenolpyruvate Carboxykinase CRISPR/Cas9-Deletion and Its Role in Trypanosoma cruzi Metacyclogenesis and Infectivity in Mammalian Host

Trypanosoma cruzi, the causative agent of Chagas disease, possesses glycosomes-unique organelles that house key metabolic enzymes, several of which are promising therapeutic targets. Among them, phosphoenolpyruvate carboxykinase (PEPCK) plays a central role in succinic fermentation, the main pathway for NAD+ regeneration within the organelle. Using CRISPR/Cas9 editing, the PEPCK gene was disrupted in T. cruzi, …

Cage-Side Blood Collections from the Ear Can Be Used for Hematological Evaluations in Japanese Macaques (Macaca fuscata)

  Japanese macaques (Macaca fuscata) are used in biomedical research where frequent, small-volume blood sampling for monitoring the animal’s health may be required. Femoral blood collected under anesthesia is the standard for obtaining CBC analyses from nonhuman primates to assess their health. However, anesthetizing animals to obtain these collections may not be ideal due to …

Integrated Approaches to Surveillance of Lymphatic Filariasis and Other Infectious Diseases in the Pacific Islands

Lymphatic filariasis (LF) is a mosquito-borne neglected tropical disease targeted by the World Health Organization (WHO) for global elimination as a public health problem. Sixteen Pacific Island countries and territories were historically endemic, and eight have now met the WHO criteria for elimination as a public health problem. Elimination as a public health problem does …

No effector is an island: joint action of Toxoplasma gondii secreted effectors in host immune subversion

Combinatorial suppression of IFN-γ signaling by T. gondii nuclear effectors.   The molecular dialogue between host and pathogen is defined by competition for the intracellular niche. Toxoplasma gondii exemplifies this mastery by deploying secreted effectors to remodel host cell biology and neutralize immune defenses. Yet a striking paradox has emerged, in which, despite exporting only …