A5071031273- Clostridium difficile and Clostridium perfringens research
- Viral gastroenteritis research and epidemiology
- Child Nutrition and Water Access
- Escherichia coli research studies
- Gut microbiota and health
- Immune cells in cancer
- Sphingolipid Metabolism and Signaling
- Gastrointestinal motility and disorders
- Peroxisome Proliferator-Activated Receptors
- Parasitic Infections and Diagnostics
- Trace Elements in Health
- Microscopic Colitis
- Child Nutrition and Feeding Issues
- Infant Nutrition and Health
- Cholesterol and Lipid Metabolism
- Transgenic Plants and Applications
- Immune Response and Inflammation
- Helicobacter pylori-related gastroenterology studies
- Advanced Glycation End Products research
- Antibiotic Resistance in Bacteria
- Adipokines, Inflammation, and Metabolic Diseases
- NF-κB Signaling Pathways
- Salmonella and Campylobacter epidemiology
- Drug Transport and Resistance Mechanisms
- Plant tissue culture and regeneration
University of Virginia
2014-2023
Center for Global Health
2013-2021
Office of Infectious Diseases
2013-2014
Indiana University School of Medicine
2013-2014
Charlottesville Medical Research
2013-2014
Wake Forest University
2010
Catholic Kwandong University
2008
University of Kentucky
2008
Cardiovascular Research Center
2007
Stanford University
2005
Critical to the design and assessment of interventions for enteropathy its developmental consequences in children living impoverished conditions are non-invasive biomarkers that can detect intestinal damage predict effects on growth development. We therefore assessed fecal, urinary systemic predictors 375 6-26 month-old with varying degrees malnutrition (stunting or wasting) Northeast Brazil. 301 these returned followup anthropometry after 2-6m. Biomarkers correlated stunting included plasma...
The use of the edible photosynthetic cyanobacterium Arthrospira platensis (spirulina) as a biomanufacturing platform has been limited by lack genetic tools. Here we report engineering methods for stable, high-level expression bioactive proteins in spirulina, including large-scale, indoor cultivation and downstream processing methods. Following targeted integration exogenous genes into spirulina chromosome (chr), encoded protein biopharmaceuticals can represent much 15% total biomass, require...
Background: Environmental enteropathy, which is linked to undernutrition and chronic infections, affects the physical mental growth of children in developing areas worldwide. Key understanding how these factors combine shape developmental outcomes first understand effects nutritional deficiencies on mammalian system including effect gut microbiota. Objective: We dissected components environmental enteropathy by analyzing specific metabolic gut-microbiota changes that occur weaned-mouse...
We have shown that the 12/15-lipoxygenase (12/15-LO) product 12<i>S</i>-hydroxyeicosatetraenoic acid increases monocyte adhesion to human endothelial cells (EC) <i>in vitro</i>. Recent studies implicated 12/15-LO in mediating atherosclerosis mice. generated transgenic mice on a C57BL/6J (B6) background modestly overexpressed murine gene (designated LOTG). LOTG had 2.5-fold elevations levels of and 2-fold increase expression protein vivo</i>. These developed spontaneous aortic fatty streak...
Endothelial activation and monocyte adhesion to endothelium are key events in inflammation. Sphingosine-1-phosphate (S1P) is a sphingolipid that binds G protein-coupled receptors on endothelial cells (ECs). We examined the role of S1P modulating monocyte-EC interactions vivo.We injected C57BL/6J mice intravenously with tumor necrosis factor (TNF)-alpha presence absence S1P1 receptor agonist SEW2871 adhesion. Aortas from TNF-alpha-injected had 4-fold increase number monocytes bound, whereas...
Diverse enteropathogen exposures associate with childhood malnutrition. To elucidate mechanistic pathways whereby enteric microbes interact during malnutrition, we used protein deficiency in mice to develop a new model of co-enteropathogen enteropathy. Focusing on common enteropathogens malnourished children, Giardia lamblia and enteroaggregative Escherichia coli (EAEC), provide insights into intersecting pathogen-specific mechanisms that enhance We show for the first time intestinal...
Abstract 5-Fluorouracil (5-FU) is an anticancer agent whose main side effects include intestinal mucositis associated with motility alterations maybe due to effect on the enteric nervous system (ENS), but underlying mechanism remains unclear. In this report, we used animal model investigate participation of S100B/RAGE/NFκB pathway in and neurotoxicity caused by 5-FU (450 mg/kg, IP, single dose). induced damage observed shortened villi, loss crypt architecture intense inflammatory cell...
Enteroaggregative Escherichia coli (EAEC) is increasingly recognized as a major cause of diarrheal disease globally. In the current study, we investigated impact zinc deficiency on host and pathogenesis EAEC. Several outcomes EAEC infection were including weight loss, shedding tissue burden, leukocyte recruitment, intestinal cytokine expression, virulence expression pathogen in vivo. Mice fed protein source defined deficient diet (dZD) had an 80% reduction serum 50% luminal contents bowel...
Atherosclerosis is a major complication of diabetes. Up to 16 weeks age, the db/db mouse insulin-resistant and hyperglycemic good model Type 2 After ∼16 mice develop pancreatic beta cell failure that can progress 1 diabetes phenotype. We have previously shown glucose increases production endothelial 12/15 lipoxygenase (12/15LO) products in vitro. In young 10-week-old diabetic mice, we found significant elevations levels urinary 12/15LO products, 12S-hydroxyeicosatetraenoic acid (12S-HETE)...
12/15-lipoxygenase (12/15-LO) activity leads to the production of proinflammatory eicosanoids 12-S-hydroxyeicosatetraenoic acid (12SHETE) and 13-S-hydroxyoctadecadienoic acid. We have previously shown a 3.5-fold increase in endothelial intercellular adhesion molecule (ICAM)-1 expression mice overexpressing 12/15-LO gene. examined whether regulated ICAM-1 expression.Freshly isolated aortic cells (EC) from transgenic had significantly greater nuclear factor-kappaB (NF-kappaB) activation ICAM...
Monocyte recruitment and adhesion to vascular endothelium are key early events in atherosclerosis. We examined the role of sphingosine-1-phosphate (S1P) on modulating monocyte/endothelial interactions NOD/LtJ (NOD) mouse model type 1 diabetes. Aortas from nondiabetic diabetic NOD mice were incubated absence or presence 100 nmol/L S1P. Fluorescently labeled monocytes with aortas. bound 7-fold more than littermates (10+/-1 bound/field for vs 74+/-12 mice, P<0.0001). Incubation aortas S1P...
G2A is a stress-inducible G protein-coupled receptor that expressed on several cell types within atherosclerotic lesions. We demonstrated previously deficiency in mice increased aortic monocyte recruitment and monocyte:endothelial interactions. To investigate the impact of macrophages, we isolated peritoneal macrophages from G2A(+/+)ApoE(-/-) G2A(-/-)ApoE(-/-) mice. had significantly lower apoptosis than control macrophages. The prosurvival genes BCL-2, BCL-xL, cFLIP were Macrophages also...
Campylobacter infections are among the leading bacterial causes of diarrhea and 'environmental enteropathy' (EE) growth failure worldwide. However, lack an inexpensive small animal model enteric disease with has been a major limitation for understanding its pathogenesis, interventions or vaccine development. We describe robust standard mouse that can exhibit reproducible bloody failure, depending on zinc protein deficient diet antibiotic alteration normal microbiota prior to infection. Zinc...
Shigella is one of the major enteric pathogens worldwide. We present a murine model S. flexneri infection and investigate role zinc deficiency (ZD). C57BL/6 mice fed either standard chow (HC) or ZD diets were pretreated with an antibiotic cocktail received strain 2457T orally. Antibiotic pre-treated showed higher colonization than non-treated mice. persistent for at least 50 days post-infection (pi). flexneri-infected significant weight loss, diarrhea increased levels fecal MPO LCN in both...
Fecal biomarkers have emerged as important tools to assess intestinal inflammation and enteropathy. The aim of this study was investigate the correlations between fecal markers, myeloperoxidase (MPO), lactoferrin (FL), calprotectin (FC) lipocalin-2 (Lcn-2), compare differences by breastfeeding status well normalization protein or weight. Simultaneous, quantitative MPO, FL, FC Lcn-2, levels were determined in frozen specimens collected from 78 children (mean age 15.2 ± 5.3 months) a...
Malnutrition and cryptosporidiosis form a vicious cycle lead to acute long-term growth impairment in children from developing countries. Insights into mechanisms underlying the will help design rational therapies mitigate this infection. We tested effect of short-term protein malnutrition on Cryptosporidium parvum infection murine model by examining stool shedding, tissue burden, histologic change explored mechanism interaction between through immunostaining immunoblotting. Protein increased...
Enteropathogenic E. coli (EPEC) are recognized as one of the leading bacterial causes infantile diarrhea worldwide. Weaned C57BL/6 mice pretreated with antibiotics were challenged orally wild-type EPEC or escN mutant (lacking type 3 secretion system) to determine colonization, inflammatory responses and clinical outcomes during infection. Antibiotic disruption intestinal microbiota enabled efficient colonization by resulting in growth impairment diarrhea. Increase biomarkers, chemokines,...
Enteroaggregative Escherichia coli (EAEC) is a major pathogen worldwide, associated with diarrheal disease in both children and adults, suggesting the need for new preventive therapeutic treatments. We investigated role of micronutrient zinc pathogenesis an E. strain human disease. A variety bacterial characteristics—growth vitro, biofilm formation, adherence to IEC-6 epithelial cells, gene expression putative EAEC virulence factors as well EAEC-induced cytokine by HCT-8 cells—were...
Clostridium difficile is a major identifiable and treatable cause of antibiotic-associated diarrhea. Poor nutritional status contributes to mortality through weakened host defenses against various pathogens. The primary goal this study was assess the contribution reduced protein diet outcomes C. infection in murine model.C57BL/6 mice were fed traditional house chow or defined with either 20% 2% infected strain VPI10463. Animals monitored for disease severity, clostridial shedding fecal toxin...
Enterotoxigenic Escherichia coli (ETEC) is a major cause of traveler's diarrhea as well endemic and stunting in children developing areas. However, small-mammal model has been badly needed to better understand assess mechanisms, vaccines, interventions. We report murine ETEC diarrhea, weight loss, enteropathy investigate the role zinc outcomes. strains producing heat-labile toxins (LT) heat-stable (ST) that were given weaned C57BL/6 mice after antibiotic disruption normal microbiota caused...
Activated endothelium and increased monocyte-endothelial interactions in the vessel wall are key early events atherogenesis. ATP binding cassette (ABC) transporters play important roles regulating sterol homeostasis many cell types. Endothelial cells (EC) have a high capacity to efflux sterols express ABC transporter, ABCG1. Here, we define role of ABCG1 regulation lipid inflammation aortic EC.Using EC isolated from ABCG1-deficient mice (ABCG1 KO), observed reduced cholesterol high-density...
Enteroaggregative Escherichia coli (EAEC) is increasingly recognized as a common cause of diarrhoea in healthy, malnourished and immune-deficient adults children. There no reproducible non-neonatal animal model for longitudinal studies disease mechanism or therapy. Using two strains human-derived EAEC to challenge weaned C57BL/6 mice, we explored an vivo infection which was monitored quantitatively the growth rate, stool shedding tissue burden organisms; nutritional status varied, new class...