A5044804416- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Biochemical and Molecular Research
- Calcium signaling and nucleotide metabolism
- Helminth infection and control
- Lysosomal Storage Disorders Research
- Immune Cell Function and Interaction
- Parasites and Host Interactions
- Signaling Pathways in Disease
- Insect symbiosis and bacterial influences
- Peptidase Inhibition and Analysis
- Cardiomyopathy and Myosin Studies
- Neuropeptides and Animal Physiology
- Synthesis and Biological Evaluation
- Lignin and Wood Chemistry
- Lipid metabolism and biosynthesis
- Parasite Biology and Host Interactions
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Kruppel-like factors research
- Biotin and Related Studies
- Toxoplasma gondii Research Studies
- Parasitic infections in humans and animals
- Malaria Research and Control
- Ferrocene Chemistry and Applications
- interferon and immune responses
Harvard University
2015-2024
Harvard University Press
2018
Kyowa Kirin (France)
2013
Iowa State University
2005
Yale University
1995-2000
International Centre of Insect Physiology and Ecology
1996
Western University
1996
Jefferson College
1993
Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed emergence of two zoonotic, highly pathogenic HCoVs: acute syndrome (SARS-CoV) and ...Read More
Cardiac hypertrophy is a common response to injury and hemodynamic stress an important harbinger of heart failure death. Herein, we identify the Kruppel-like factor 15 (KLF15) as inhibitor cardiac hypertrophy. Myocardial expression KLF15 reduced in rodent models biopsy samples from patients with pressure-overload induced by chronic valvular aortic stenosis. Overexpression neonatal rat ventricular cardiomyocytes inhibits cell size, protein synthesis hypertrophic gene expression. KLF15-null...
Intracellular colonization and persistent infection by the kinetoplastid protozoan parasite, Trypanosoma cruzi, underlie pathogenesis of human Chagas disease. To obtain global insights into T. cruzi infective process, transcriptome dynamics were simultaneously captured in parasite host cells an time course fibroblasts. Extensive remodeling was observed during early establishment intracellular infection, coincident with a major developmental transition parasite. Contrasting this response, few...
IFN-γ is a major cytokine that mediates resistance against the intracellular parasite Toxoplasma gondii. The p65 guanylate-binding proteins (GBPs) are strongly induced by IFN-γ. We studied behavior of murine GBP1 (mGBP1) upon infection with T. gondii in vitro and confirmed IFN-γ-dependent re-localization mGBP1 to parasitophorous vacuole (PV) correlates virulence type parasite. identified three parasitic factors, ROP16, ROP18, GRA15 determine strain-specific accumulation on PV. These highly...
Mammalian cell invasion by the protozoan parasite, Trypanosoma cruzi, is facilitated activation of host phosphatidylinositol 3 (PI 3)-kinases. We demonstrate that well-characterized Ca2+-regulated lysosome-mediated parasite entry pathway abolished wortmannin pretreatment. In addition, we have characterized a novel route T. cruzi unexpectedly revealed in course this study. For over decade, targeted exocytosis lysosomes at plasma membrane was considered as primary mechanism for into...
An early event in the Trypanosoma cruzi cell invasion process, recruitment of host lysosomes, led us to investigate involvement signal transduction. Infective trypomastigotes were found contain a soluble Ca2+-signaling activity for mammalian cells that is sensitive protease inhibitors. Inhibitor and substrate utilization profiles used purify candidate peptidase this from which we isolated full-length cDNA clone. The sequence revealed novel enzyme, denominated T. oligopeptidase B, homologous...
Novel technologies that include recombinant pathogens and rapid detection methods are contributing to the development of drugs for neglected diseases. Recently, results from first high throughput screening (HTS) test compounds activity against Trypanosoma cruzi trypomastigote infection host cells were reported. We have selected 23 hits this HTS, which reported anti-trypanosomal low toxicity cells. These highly purified their structures confirmed by HPLC/mass spectrometry. The tested in...
Obligate intracellular pathogens satisfy their nutrient requirements by coupling to host metabolic processes, often modulating these pathways facilitate access key metabolites. Such dependencies represent potential targets for pathogen control, but remain largely uncharacterized the protozoan parasite and causative agent of Chagas disease, Trypanosoma cruzi. Perturbations in central carbon energy metabolism have been reported mammalian T. cruzi infection, with no information regarding impact...
, a zoonotic kinetoplastid protozoan parasite, is the causative agent of American trypanosomiasis (Chagas disease). Having very plastic, repetitive and complex genome, parasite displays highly diverse repertoire surface molecules, with pivotal roles in cell invasion, immune evasion pathogenesis. Before 2016, complexity genomic regions containing these genes impaired assembly genome at chromosomal level, making it impossible to study structure function several thousand encoding molecules...
Host cell infection by the intracellular pathogen, <i>Trypanosoma cruzi</i>, involves activation of signaling pathways, cytoskeletal reorganization, and targeted recruitment host lysosomes. To determine consequences of<i>T. cruzi</i> invasion on gene expression, high density microarrays consisting ∼27,000 human cDNAs were hybridized with fluorescent probes generated from <i>T. cruzi</i>-infected fibroblasts (HFF) at early time points following (2–24 h). Surprisingly, no genes induced ≥2-fold...
Trypomastigotes, the infective stages of intracellular parasite Trypanosoma cruzi, induce rapid and repetitive cytosolic free Ca2+ transients in fibroblasts. Buffering or depletion inhibits cell entry by trypomastigotes, indicating a role for this signaling event invasion. We show here that majority Ca2+-signaling activity is associated with soluble fraction parasites disrupted sonication. Distinct types from different species are responsive to factor, occur rapidly reach concentrations...
To evaluate the possibility of an underlying dimension organicity in borderline personality disorder (BPD), a carefully diagnosed group patients was assessed across wide range neuropsychological functions and then compared to age- education-matched non-patient control group. The BPD had significantly lower Verbal, Performance, Full Scale IQ scores on WAIS-R. also impaired motor skills, figural memory, complex visuomotor integration, social or interpersonal intelligence, measure...
Innate immunity is the first line of defense against invading microorganisms. Trypanosome Lytic Factor (TLF) a minor sub-fraction human high-density lipoprotein that provides innate by completely protecting humans from infection most species African trypanosomes, which belong to Kinetoplastida order. Herein, we demonstrate broader protective effects TLF, inhibits intracellular Leishmania, kinetoplastid replicates in phagolysosomes macrophages. We show TLF accumulates within parasitophorous...
Trypanosoma cruzi, the protozoan that causes Chagas disease, has a complex life cycle involving several morphologically and biochemically distinct stages establish intricate interactions with various insect mammalian hosts. It also heterogeneous population structure comprising strains properties such as virulence, sensitivity to drugs, antigenic profile tissue tropism. We present comparative transcriptome analysis of two cloned T. cruzi display contrasting virulence phenotypes in animal...
The mammalian stages of the parasite
One of the hallmarks Trypanosoma cruzi invasion non-professional phagocytes is facilitation process by host cell actin depolymerization. Host entry invasive T. trypomastigotes accomplished exploiting a cellular wound repair involving Ca2+-regulated lysosome exocytosis (i.e. lysosome-dependent) or engaging recently recognized lysosome-independent pathway. It was originally postulated that cortical microfilaments present barrier to lysosome-plasma membrane fusion and transient depolymerization...
Intracellular infection and multi-organ colonization by the protozoan parasite, Trypanosoma cruzi, underlie complex etiology of human Chagas disease. While T. cruzi can establish cytosolic residence in a broad range mammalian cell types, molecular mechanisms governing this process remain poorly understood. Despite anticipated capacity for fatty acid synthesis recent observations suggest that intracellular amastigotes may rely on host metabolism to support infection. To investigate...
<i>Trypanosoma brucei</i> contains a soluble serine oligopeptidase (OP-Tb) that is released into the host bloodstream during infection, where it has been postulated to participate in pathogenesis of African trypanosomiasis. Here, we report identification single copy gene encoding <i>T. and homologue from related trypanosomatid pathogen <i>Leishmania major.</i> The enzymes encoded by these genes belong an emerging subgroup prolyl family hydrolases, referred as B. oligopeptidases share 70%...