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Author: Donna Huber

Chemical Optimization of CBL0137 for Human African Trypanosomiasis Lead Drug Discovery

The carbazole CBL0137 (1) is a lead for drug development against human African trypanosomiasis (HAT), a disease caused by Trypanosoma brucei. To advance 1 as a candidate drug, we synthesized new analogs that were evaluated for the physicochemical properties, antitrypanosome potency, selectivity against human cells, metabolism in microsomes or hepatocytes, and efflux ratios. Structure-activity/property analyses of analogs revealed …

TriTrypDB: An integrated functional genomics resource for kinetoplastida

Parasitic diseases caused by kinetoplastid parasites are a burden to public health throughout tropical and subtropical regions of the world. TriTrypDB (https://tritrypdb.org) is a free online resource for data mining of genomic and functional data from these kinetoplastid parasites and is part of the VEuPathDB Bioinformatics Resource Center (https://veupathdb.org). As of release 59, TriTrypDB hosts …

Praziquantel target validation of a Ca2+ permeable channel in schistosomes

Highlights Schistosomiasis is a devastating neglected helminthic disease. Praziquantel (PZQ) is the most important drug against schistosomiasis. Previous work identified a TRP channel of the melastatin type as a PZQ target. Molecular studies now reveal the basis for varied PZQ sensitivity of different helminths. Roberto Docampo. Cell Calcium. 2023 Jan 18;110:102698. doi: 10.1016/j.ceca.2023.102698

Malaria disrupts the rhesus macaque gut microbiome

Previous studies have suggested that a relationship exists between severity and transmissibility of malaria and variations in the gut microbiome, yet only limited information exists on the temporal dynamics of the gut microbial community during a malarial infection. Here, using a rhesus macaque model of relapsing malaria, we investigate how malaria affects the gut microbiome. …

Epitopes in the Glycosylphosphatidylinositol Attachment Signal Peptide of Trypanosoma cruzi Mucin Proteins Generate Robust But Delayed and Nonprotective CD8+ T Cell Responses

Infection with the protozoan parasite Trypanosoma cruzi elicits substantial CD8+ T cell responses that disproportionately target epitopes encoded in the large trans-sialidase (TS) gene family. Within the C57BL/6 infection model, a significant proportion (30-40%) of the T. cruzi-specific CD8+ T cell response targets two immunodominant TS epitopes, TSKb18 and TSKb20. However, both TS-specific CD8+ T …

AIM2 sensors mediate immunity to Plasmodium infection in hepatocytes

Malaria, caused by Plasmodium parasites is a severe disease affecting millions of people around the world. Plasmodium undergoes obligatory development and replication in the hepatocytes, before initiating the life-threatening blood-stage of malaria. Although the natural immune responses impeding Plasmodium infection and development in the liver are key to controlling clinical malaria and transmission, those remain relatively unknown. Here we demonstrate that …

B cell responses in chronic Chagas disease: Waning of Trypanosoma cruzi-specific antibody-secreting cells following successful etiological treatment

Background: A drawback in the treatment of chronic Chagas disease (American trypanosomiasis) is the long time required to achieve complete loss of serological reactivity, the standard for determining treatment efficacy. Methods: Antibody-secreting and memory B cells specific for Trypanosoma cruzi and their degree of differentiation were evaluated in adult and pediatric subjects with chronic Chagas disease prior …

In Vitro Diagnostic Assay to Detect SARS-CoV-2-Neutralizing Antibody in Patient Sera Using Engineered ACE-2 Mini-Protein

The recent development and mass administration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines allowed for disease control, reducing hospitalizations and mortality. Most of these vaccines target the SARS-CoV-2 Spike (S) protein antigens, culminating with the production of neutralizing antibodies (NAbs) that disrupt the attachment of the virus to ACE2 receptors on the host …

The CTEGD Cytometry Shared Resource Lab is growing!

CTEGD's Cytometry Shared Resource Laboratory recently added a Malvern Panalytical NanoSight NS300 to their suite of cytometry instruments. This was a donation from the laboratory of Dr. Stephen Hajduk. The NanoSight allows rapid analysis of the size distribution and concentration of all types of nanoparticles from 0.01 - 1 µm in diameter.  It is important …