A5026922666- Clostridium difficile and Clostridium perfringens research
- Gut microbiota and health
- Microscopic Colitis
- Malaria Research and Control
- Drug Transport and Resistance Mechanisms
- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Neuroendocrine regulation and behavior
- Helicobacter pylori-related gastroenterology studies
- Pharmacological Effects and Toxicity Studies
- Gastrointestinal motility and disorders
- Bioinformatics and Genomic Networks
- Ginger and Zingiberaceae research
- Fungal and yeast genetics research
- Pediatric health and respiratory diseases
- Vector-borne infectious diseases
- Fermentation and Sensory Analysis
- Nosocomial Infections in ICU
- Genetic Neurodegenerative Diseases
- Religion, Society, and Development
- Complement system in diseases
- Bird parasitology and diseases
- Fungal Biology and Applications
- Nonmelanoma Skin Cancer Studies
- Tryptophan and brain disorders
University of Pennsylvania
2020-2025
National Institutes of Health
2024
National Human Genome Research Institute
2024
University of Louisville
2015-2023
California University of Pennsylvania
2023
Vanderbilt University
2019-2020
Vanderbilt University Medical Center
2018
University of Tennessee at Knoxville
2015-2016
Carson Newman University
2013-2014
Plasmodium infections result in clinical presentations that range from asymptomatic to severe malaria, resulting ∼1 million deaths annually. Despite this toll on humanity, the factors determine disease severity remain poorly understood. Here, we show gut microbiota of mice influences pathogenesis malaria. Genetically similar different commercial vendors, which exhibited differences their bacterial community, had significant parasite burden and mortality after infection with multiple species....
Fecal microbiota transplantation (FMT) is a successful therapeutic strategy for treating recurrent Clostridioides difficile infection. Despite remarkable efficacy, implementation of FMT therapy limited and the mechanism action remains poorly understood. Here, we demonstrate critical role immune system in supporting using murine C. infection system. Following FMT, Rag1 heterozygote mice resolve while littermate Rag1-/- fail to clear Targeted ablation adaptive cell subsets reveal necessary...
C57BL/6 mice are widely used for in vivo studies of immune function and metabolism mammals. In a previous study, it was observed that when purchased from different vendors were infected with Plasmodium yoelii, causative agent murine malaria, they exhibited both differential responses significantly parasite burdens: these patterns reproducible gut contents transplanted into gnotobiotic mice. To gain insight the mechanism resistance, we removed whole ceca two vendors, Taconic Biosciences (low...
ABSTRACT Clostridioides difficile infects the large intestine and can result in debilitating potentially fatal colitis. The intestinal microbiota is a major factor influencing severity of disease following infection. Factors like diet that shape composition function may modulate C. Here, we report mice fed two distinct standard mouse chows (LabDiet 5010 LabDiet 5053) exhibited significantly different susceptibility to severe Both diets are grain-based with comparable profiles macro...
Abstract Experimental models of malaria have shown that infection with specific Plasmodium species in certain mouse strains can transiently modulate gut microbiota and cause intestinal shortening, indicating a disruption homeostasis. Importantly, changes homeostasis not been characterized the context mild versus severe malaria. We show mice disrupts along gut-liver axis multiple ways compared to infection. High parasite burden results larger influx immune cells lamina propria high...
Gut microbiota educate the local and distal immune system in early life to imprint long-term immunological outcomes while maintaining capacity dynamically modulate mucosal throughout life. It is unknown whether gut provide signals that regulate responses following an extra-gastrointestinal infection. We show here bacteria composition correlated with severity of malaria children. Using murine model malaria, we demonstrate parasite burden spleen germinal center reactions are malleable dynamic...
Clostridioides difficile infection causes pathology that ranges in severity from diarrhea to pseudomembranous colitis. Toxin A and B are the two primary virulence factors secreted by C. drive disease severity. The toxins damage intestinal epithelial cells leading a loss of barrier integrity induction proinflammatory host response. Monoclonal antibodies (mAbs) neutralize B, actoxumab bezlotoxumab, respectively, significantly reduce murine model infection. However, impact toxin neutralization...
Gut microbiota composition is associated with human and rodent Plasmodium infections, yet the mechanism by which gut affects severity of malaria remains unknown. Humoral immunity critical in mediating clearance blood stage prompting hypothesis that mice microbiota-dependent decreases parasite burden exhibit better germinal center (GC) responses. In support this hypothesis, a low increases GC B cell numbers parasite-specific antibody titers, as well maintenance structures more targeted,...
ABSTRACT Background Current approaches to predicting Cardiovascular disease rely on conventional risk factors and cross-sectional data. In this study, we asked whether: i) machine learning deep models with longitudinal EHR information can improve the prediction of 10-year CVD risk, ii) incorporating genetic data add values predictability. Methods We conducted two experiments. first experiment, modeled aggregated features temporal features. applied logistic regression (LR), random forests...
Experimental reproducibility in mouse models is impacted by both genetics and environment. The generation of reproducible data critical for the biomedical enterprise has become a major concern scientific community funding agencies alike. Among factors that impact experimental variable composition microbiota mice supplied different commercial vendors. Less attention been paid to how particular vendor might change over time. In course conducting series experiments model malaria, we observed...
Infection with the bacterial pathogen
There is an urgent need for new antimalarial agents and strategies to treat control malaria. This study shows antiplasmodium effect of tulathromycin in mice infected with Plasmodium yoelii. The administration around the time infection prevented progression disease 100% animals. In addition, highly parasitized treated showed a decreased parasite burden cleared faster than did untreated mice.
Abstract Malaria is an infectious disease responsible for the death of around 450,000 people annually. As effective vaccine against parasite that causes malaria not available, antimalarial drug treatments are critical in fighting disease. Previous data has shown gut microbiota important modulating severity malaria. Although it well appreciated antibiotics substantially alter microbiota, largely unknown how drugs impact microbiota. We show here two commonly used artemisinin combination...
Abstract Summary Electronic health records (EHRs) linked with a DNA biobank provide unprecedented opportunities for biomedical research in precision medicine. The Phenome-wide association study (PheWAS) is widely used technique the evaluation of relationships between genetic variants and large collection clinical phenotypes recorded EHRs. PheWAS analyses are typically presented as static tables charts summary statistics obtained from statistical tests variant individual phenotypes....
Many fungi have evolved mechanisms to assess environmental nutrient availability prior the energy-intensive process of mating. In this study, we examined one such system in Saccharomyces cerevisiae, involving a glucose-sensing pathway mediated by Gpr1p and pheromone-induced mating pathway. Initially observed that MATa cells is sensitive glucose depletion. This phenomenon can be partially reversed with high spike, but not addition low levels glucose. Deletion low-affinity receptor, Gpr1p,...
Clostridioides difficile is an enteric bacterial pathogen that can a cause nosocomial infection leading to debilitating colitis. The development of murine model C. has led fundamental discoveries in disease pathogenesis and the host immune response infection. Recently, endogenously present microbiota mice been reported was found complicate interpretation mouse studies. Here, we report novel strain, named NTCD-035, isolated from our colony. presence NTCD-035 prior challenge with highly...
In a recent study by Zhao et al., rare protein-truncating variants (PTVs) in the BSN and APBA1 genes showed effects on obesity that exceeded those of well-known such as MC4R UK cohort. this study, we leveraged All Us Research Program, to investigate association predicted LoF (pLoF) PTVs with body mass index (BMI) across population diverse ancestry. Our analysis revealed impact pLoF BMI was notably greater cohort, especially among individuals European Additionally, phenome-wide (PheWAS) using...
We evaluated skin cancer risk in sexual minority (SM) compared with heterosexual individuals and assessed the mediation effect of HIV status on association between SM using a national database.
Genetic variation in
Abstract Clostridioides difficile, the most common hospital acquired pathogen in United States, infects gastrointestinal tract following perturbation of intestinal microbiota causing debilitating, potentially fatal colitis. Primary C. difficile infection has a high recurrence rate antibiotic treatment, emphasizing need to develop alternative treatment strategies reduce burden on healthcare system. Innate lymphoid cells (ILCs) are necessary for acute host defense and represent promising...
Abstract Fecal microbiota transplantation (FMT) is an effective therapy for treating recurrent C. difficile infection. However, the FMT mechanism of action poorly understood, and implementation limited. A previous study from our lab identified a critical role CD4+ FoxP3+ regulatory T cells (Treg) in enabling engraftment subsequent resolution Here, we investigated cellular cytokine network regulated by Treg to support FMT-mediated On day FMT, infected mice have increased IL10+ colon compared...