A5050573667- Toxoplasma gondii Research Studies
- Herpesvirus Infections and Treatments
- Parasitic Infections and Diagnostics
- Cytomegalovirus and herpesvirus research
- Bacteriophages and microbial interactions
- Mosquito-borne diseases and control
- HIV Research and Treatment
- Autophagy in Disease and Therapy
- Rabies epidemiology and control
- Cellular transport and secretion
- Malaria Research and Control
- Trypanosoma species research and implications
- Viral Infections and Vectors
- Parasitic infections in humans and animals
- T-cell and B-cell Immunology
- Vector-Borne Animal Diseases
- Immunotherapy and Immune Responses
- Animal Disease Management and Epidemiology
University of Washington
2024
Seattle University
2024
Albert Einstein College of Medicine
2021-2023
Dartmouth College
2013-2021
Mayo Clinic
2011-2014
ABSTRACT Ingestion of the obligate intracellular protozoan parasite Toxoplasma gondii causes an acute infection that leads to chronic host. To facilitate phase infection, T. manipulates host response by secreting rhoptry organelle proteins (ROPs) into cells during its invasion. A few key ROP with signatures kinases or pseudokinases (ROPKs) act as virulence factors enhance survival against gamma interferon-stimulated innate immunity. However, roles these and other ROPK in establishing have...
Toxoplasma gondii cysts reactivate during immune deficiency and cause fatal encephalitis. Parasite molecules that coordinate the development of acute chronic infection are poorly characterized. Here, we show many intravacuolar network membrane parasitophorous vacuole membrane-associated dense granule (GRA) proteins orchestrate in vivo . A subset these GRA also modulate virulence, one protein associates with membranes, namely GRA12, was identified as a major virulence factor required for...
Nonreplicating type I uracil auxotrophic mutants of Toxoplasma gondii possess a potent ability to activate therapeutic immunity established solid tumors by reversing immune suppression in the tumor microenvironment. Here we engineered targeted deletions parasite secreted effector proteins using genetically tractable Δku80 vaccine strain show that secretion specific rhoptry (ROP) and dense granule (GRA) T. conjunction with host cell invasion activates antitumor through responses involving...
The intracellular parasite Toxoplasma gondii adapts to diverse host cell environments within a replicative compartment that is heavily decorated by secreted proteins. In an attempt identify novel proteins influence activity, we identified and characterized transmembrane dense granule protein dubbed GRA64 (TGME49_202620). We found on the parasitophorous vacuolar membrane (PVM) partially exposed cytoplasm in both tachyzoite bradyzoite vacuoles. Using co-immunoprecipitation proximity-based...
ABSTRACT BST2/tetherin inhibits the release of enveloped viruses from cells. Primate lentiviruses have evolved specific antagonists (Vpu, Nef, and Env). Here we characterized tetherin proteins species representing both branches order Carnivora. Comparison tiger cat (Feliformia) to dog ferret (Caniformia) genes demonstrated that share a start codon mutation truncated most cytoplasmic tail early in Feliformia lineage (19 27 amino acids, including dual tyrosine motif). Alpha interferon (IFN-α)...
Little is known regarding how the chronic
After differentiation is triggered, the tachyzoite-stage
ABSTRACT Intracellular pathogens exploit cellular resources through host cell manipulation. Within its nonfusogenic parasitophorous vacuole (PV), Toxoplasma gondii targets nutrient-filled organelles and sequesters them into the PV deep invaginations of membrane (PVM) that ultimately detach from this membrane. Some these are generated by an intravacuolar network (IVN) parasite-derived tubules attached to PVM. Here, we examined usurpation ESCRT-III Vps4A parasite create PVM buds vesicles....
Targeted genetic manipulation using homologous recombination is the method of choice for functional genomic analysis to obtain a detailed view gene function and phenotype(s). The development mutant strains with targeted deletions, mutations, complemented function, and/or tagged genes provides powerful strategies address particularly if these manipulations can be efficiently locus interest integration mediated by double cross over recombination. Due very high rates nonhomologous...
causes a chronic infection that renders the immunocompromised human host susceptible to toxoplasmic encephalitis triggered by cyst reactivation in central nervous system. The dense granule protein GRA12 is major parasite virulence factor required for survival during acute infection. Here, we characterized role of four GRA12-related genes and stages While GRA12A, GRA12B, GRA12D were highly expressed asexual stage tachyzoites bradyzoites, expression GRA12C appeared be restricted sexual stages....
A rodent or other small animal model for HIV-1 has not been forthcoming, with the principal obstacles being species-specific restriction mechanisms and deficits in dependency factors. Some Carnivorans may harbor comparatively fewer impediments. For example, contrast to mice, domestic cat genome encodes essential nonreceptor All Feliformia species at least one Caniformia also lack a major lentiviral mechanism (TRIM5α/TRIMCyp proteins). Here we investigated cells from two another carnivore...
The glycosylated mucin domain of the
The hetero-multimeric protein machinery known as Endosomal Sorting Complex Required for Transport (ESCRT) operates across a spectrum of major cellular pathways including endosomal sorting, intralumenal vesicle biogenesis, and repair endo-lysosomal plasma membranes. Because its pivotal roles in membrane remodeling, the ESCRT is also exploited by many viral bacterial pathogens replication intracellular survival. We recently reported that protozoan pathogen Toxoplasma gondii (Tg) subverts...
Abstract Intracellular pathogens exploit cellular resources through host cell manipulation. Within its nonfusogenic parasitophorous vacuole (PV), Toxoplasma targets nutrient-filled organelles and sequesters them into the PV deep invaginations of membrane (PVM) that ultimately detach from this membrane. Some these are generated by an intravacuolar network (IVN) parasite-derived tubules fusing with PVM. Here, we examine parasite usurpation ESCRT-III Vps4 to create PVM buds vesicles. CHMP4B...
ABSTRACT The intracellular parasite Toxoplasma gondii adapts to diverse host cell environments within a replicative compartment that is heavily decorated by secreted proteins. In attempts identify novel proteins influence activity, we identified and characterized trans-membrane dense granule protein dubbed GRA64 (TGME49_202620). We found on the parasitophorous vacuolar membrane (PVM) partially exposed cytoplasm in both tachyzoite bradyzoite vacuoles. Using co-immunoprecipitation...
Targeted genetic manipulation using homologous recombination is the method of choice for functional genomic analysis to obtain a detailed view gene function and phenotype(s). The development mutant strains with targeted deletions, mutations, complemented function, and/or tagged genes provides powerful strategies address particularly if these manipulations can be efficiently locus interest integration mediated by double cross over recombination. Due very high rates nonhomologous...