dysregulates expression profile of piRNAs in primary human cardiac fibroblasts during early infection phase.

, the etiological agent of Chagas Disease, causes severe morbidity, mortality, and economic burden worldwide. Though originally endemic to Central and South America, globalization has led to increased parasite presence in most industrialized countries. About 40% of infected individuals will develop cardiovascular, neurological, and/or gastrointestinal pathologies.

Dysregulates piRNAs Computationally Predicted to Target IL-6 Signaling Molecules During Early Infection of Primary Human Cardiac Fibroblasts.

, the etiological agent of Chagas disease, is an intracellular protozoan parasite, which is now present in most industrialized countries. About 40% of infected individuals will develop severe, incurable cardiovascular, gastrointestinal, or neurological disorders. The molecular mechanisms by which induces cardiopathogenesis remain to be determined.

Thrombospondin-1 expression and modulation of Wnt and hippo signaling pathways during the early phase of Trypanosoma cruzi infection of heart endothelial cells.

The protozoan parasite, Trypanosoma cruzi, causes severe morbidity and mortality in afflicted individuals. Approximately 30% of T. cruzi infected individuals present with cardiac pathology.

piRNAs as Modulators of Disease Pathogenesis.

Advances in understanding disease pathogenesis correlates to modifications in gene expression within different tissues and organ systems. In depth knowledge about the dysregulation of gene expression profiles is fundamental to fully uncover mechanisms in disease development and changes in host homeostasis. The body of knowledge surrounding mammalian regulatory elements, specifically regulators of chromatin structure, transcriptional and translational activation, has considerably surged within the past decade.

Modulates PIWI-Interacting RNA Expression in Primary Human Cardiac Myocytes during the Early Phase of Infection.

dysregulates the gene expression profile of primary human cardiomyocytes (PHCM) during the early phase of infection through a mechanism which remains to be elucidated. The role that small non-coding RNAs (sncRNA) including PIWI-interacting RNA (piRNA) play in regulating gene expression during the early phase of infection is unknown. To understand how dysregulate gene expression in the heart, we challenged PHCM with trypomastigotes and analyzed sncRNA, especially piRNA, by RNA-sequencing.

Thrombospondin-1 Plays an Essential Role in Yes-Associated Protein Nuclear Translocation during the Early Phase of Infection in Heart Endothelial Cells.

The protozoan parasite is the causative agent of Chagas disease. This neglected tropical disease causes severe morbidity and mortality in endemic regions. About 30% of infected individuals will present with cardiac complications.

The Research Centers in Minority Institutions (RCMI) Translational Research Network: Building and Sustaining Capacity for Multi-Site Basic Biomedical, Clinical and Behavioral Research.

The Research Centers in Minority Institutions (RCMI) program was established by the US Congress to support the development of biomedical research infrastructure at minority-serving institutions granting doctoral degrees in the health professions or in a health-related science. RCMI institutions also conduct research on diseases that disproportionately affect racial and ethnic minorities (ie, African Americans/Blacks, American Indians and Alaska Natives, Hispanics, Native Hawaiians and Other Pacific Islanders), those of low socioeconomic status, and rural persons. Quantitative metrics, including the numbers of doctoral science degrees granted to underrepresented students, NIH peer-reviewed research funding, peer-reviewed publications, and numbers of racial and ethnic minorities participating in sponsored research, demonstrate that RCMI grantee institutions have made substantial progress toward the intent of the Congressional legislation, as well as the NIH/NIMHD-linked goals of addressing workforce diversity and health disparities.

Phospho-proteomic analysis of primary human colon epithelial cells during the early Trypanosoma cruzi infection phase.

The protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease, causes severe morbidity and mortality in afflicted individuals. About 30% of T. cruzi-infected individuals present with cardiac, gastrointestinal tract, and/or neurological disorders.

Epitope Capsid-Incorporation: New Effective Approach for Vaccine Development for Chagas Disease.

Background: Previously we reported that a hexon-modified adenovirus (Ad) vector containing the invasive neutralizing epitope of ( trypomastigote gp83 (Ad5-gp83) provided immunoprotection against infection. The purpose of this work was to design an improved vaccine for using a novel epitope capsid incorporation strategy. Thus, we evaluated the immunoprotection raised by co-immunization with Ad5-gp83 and an Ad vector containing an epitope (ASP-M) of the amastigote surface protein 2.

Early Regulation of Profibrotic Genes in Primary Human Cardiac Myocytes by Trypanosoma cruzi.

The molecular mechanisms of Trypanosoma cruzi induced cardiac fibrosis remains to be elucidated. Primary human cardiomyoctes (PHCM) exposed to invasive T. cruzi trypomastigotes were used for transcriptome profiling and downstream bioinformatic analysis to determine fibrotic-associated genes regulated early during infection process (0 to 120 minutes).

Immunization with Hexon modified adenoviral vectors integrated with gp83 epitope provides protection against Trypanosoma cruzi infection.

Background: Trypanosoma cruzi is the causative agent of Chagas disease. Chagas disease is an endemic infection that affects over 8 million people throughout Latin America and now has become a global challenge. The current pharmacological treatment of patients is unsuccessful in most cases, highly toxic, and no vaccines are available.

Cellular response to Trypanosoma cruzi infection induces secretion of defensin α-1, which damages the flagellum, neutralizes trypanosome motility, and inhibits infection.

Human defensins play a fundamental role in the initiation of innate immune responses to some microbial pathogens. Here we show that colonic epithelial model HCT116 cells respond to Trypanosoma cruzi infection by secreting defensin α-1, which reduces infection. We also report the early effects of defensin α-1 on invasive trypomastigotes that involve damage of the flagellar structure to inhibit parasite motility and reduce cellular infection.

Regulation and use of the extracellular matrix by Trypanosoma cruzi during early infection.

Chagas disease, which was once thought to be confined to endemic regions of Latin America, has now gone global becoming a new worldwide challenge. For more than a century since its discovery, it has remained neglected with no effective drugs or vaccines. The mechanisms by which Trypanosoma cruzi regulates and uses the extracellular matrix (ECM) to invade cells and cause disease are just beginning to be understood.

Thrombospondin-1 interacts with Trypanosoma cruzi surface calreticulin to enhance cellular infection.

Trypanosoma cruzi causes Chagas disease, which is a neglected tropical disease that produces severe pathology and mortality. The mechanisms by which the parasite invades cells are not well elucidated. We recently reported that T.

Gene network analysis during early infection of human coronary artery smooth muscle cells by Trypanosoma cruzi and Its gp83 ligand.

Trypanosoma cruzi, the causative agent of Chagas' disease, infects heart and muscle cells leading to cardiac arrest, followed by death. The genetic architectures in the early T. cruzi infection process of human cells are unknown.

REGULATION of the EXTRACELLULAR MATRIX INTERACTOME by Trypanosoma cruzi.

It has been shown that the invasive trypomastigote forms of Trypanosoma cruzi use and modulate components of the extracellular matrix (ECM) during the initial process of infection. Infective trypomastigotes up-regulate the expression of laminin γ-1 (LAMC1) and thrombospondin (THBS1) to facilitate the recruitment of trypomastigotes to enhance cellular infection. Silencing the expression of LAMC1 and THBS1 by stable RNAi dramatically reduces trypanosome infection.

Perspectives on the Trypanosoma cruzi-host cell receptor interactions.

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions.

Molecular analysis of early host cell infection by Trypanosoma cruzi.

Trypanosoma cruzi, the causative agent of Chagas heart disease, infects heart and other cells leading to cardiac arrest frequently followed by death. The disease affects millions of individuals in the Americas and is posing health problems because of blood transmission in the US due to large Latin American immigration. Since the current drugs present serious side effects and do not cure the chronic infection, it is critically important to understand the early process of cellular infection at the molecular and structural levels to design novel inhibitors to block T.

Human defensin alpha-1 causes Trypanosoma cruzi membrane pore formation and induces DNA fragmentation, which leads to trypanosome destruction.

Human defensins play a fundamental role in the initiation of innate immune responses to some microbial pathogens. Here we show that human defensin alpha-1 displays a trypanocidal role against Trypanosoma cruzi, the causative agent of Chagas' disease. The toxicity of human defensin alpha-1 against T.

Molecular cloning of a Trypanosoma cruzi cell surface casein kinase II substrate, Tc-1, involved in cellular infection.

In this work, we report the cloning and characterization of the first cell surface casein kinase II (CKII) substrate (Tc-1) of Trypanosoma cruzi, the causative agent of Chagas' disease. Analysis of the gene sequence revealed a 1,653-bp open reading frame coding for 550 amino acid residues. Northern blot analysis showed a 4.

Stable RNA interference of host thrombospondin-1 blocks Trypanosoma cruzi infection.

Interactions between Trypanosoma cruzi and the extracellular matrix play an important role in cellular invasion. Here we show that T. cruzi increases the levels of thrombospondin-1 (TSP-1) expression in host cells during early infection.

Silencing of the laminin gamma-1 gene blocks Trypanosoma cruzi infection.

It is thought that Trypanosoma cruzi, the protozoan that causes Chagas' disease, modulates the extracellular matrix network to facilitate infection of human cells. However, direct evidence to document this phenomenon is lacking. Here we show that the T.

Human galectin-3 promotes Trypanosoma cruzi adhesion to human coronary artery smooth muscle cells.

Human galectin-3 binds to the surface of Trypanosoma cruzi trypomastigotes and human coronary artery smooth muscle (CASM) cells. CASM cells express galectin-3 on their surface and secrete it. Exogenous galectin-3 increased the binding of T.

Transforming growth factor alpha binds to Trypanosoma cruzi amastigotes to induce signaling and cellular proliferation.

Macrophages secrete transforming growth factor alpha (TGF-alpha) to trigger proliferation of cancer cells. Here, we report a new role for TGF-alpha in modulating the direct cellular proliferation of a parasitic protozoan, Trypanosoma cruzi. Amastigotes present two classes of receptors for TGF-alpha with different binding affinities.