A5063936502- Amoebic Infections and Treatments
- Pancreatitis Pathology and Treatment
- Clostridium difficile and Clostridium perfringens research
- Immune responses and vaccinations
- Gut microbiota and health
- Microscopic Colitis
- IL-33, ST2, and ILC Pathways
- SARS-CoV-2 and COVID-19 Research
- Parasitic Infections and Diagnostics
- COVID-19 Clinical Research Studies
- Immune Cell Function and Interaction
- Diagnosis and treatment of tuberculosis
- Inflammasome and immune disorders
- Eosinophilic Esophagitis
- Long-Term Effects of COVID-19
- Helicobacter pylori-related gastroenterology studies
- Child Nutrition and Water Access
- Diet and metabolism studies
- Digestive system and related health
- Respiratory Support and Mechanisms
- Pediatric health and respiratory diseases
- Dietary Effects on Health
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- Thermal Regulation in Medicine
University of Virginia
2014-2024
University of Virginia Health System
2014-2021
Office of Infectious Diseases
2021
Cincinnati Children's Hospital Medical Center
2011-2013
University of Cincinnati Medical Center
2013
Murine models of SARS-CoV-2 infection are critical for elucidating the biological pathways underlying COVID-19. Because human angiotensin-converting enzyme 2 (ACE2) is receptor SARS-CoV-2, mice expressing ACE2 gene have shown promise as a potential model Five from transgenic mouse strain K18-hACE2 were intranasally inoculated with Hong Kong/VM20001061/2020. Mice followed twice daily 5 days and scored weight loss clinical symptoms. Infected did not exhibit any signs until day 4, when no other...
Immune dysregulation is characteristic of the more severe stages SARS-CoV-2 infection. Understanding mechanisms by which immune system contributes to COVID-19 severity may open new avenues treatment. Here, we report that elevated IL-13 was associated with need for mechanical ventilation in 2 independent patient cohorts. In addition, patients who acquired while prescribed Dupilumab, a mAb blocks and IL-4 signaling, had less disease. SARS-CoV-2–infected mice, neutralization reduced death...
Background. An estimated 1 million children die each year before their fifth birthday from diarrhea. Previous population-based surveys of pediatric diarrheal diseases have identified the protozoan parasite Entamoeba histolytica, etiological agent amebiasis, as one causes moderate-to-severe diarrhea in sub-Saharan Africa and South Asia.
There is an emerging paradigm that the human microbiome central to many aspects of health and may have a role in preventing enteric infection. Entamoeba histolytica major cause amebic diarrhea developing countries. It colonizes colon lumen close proximity gut microbiota. Interestingly, not all individuals are equally susceptible E. Therefore, as microbiota highly variable within individuals, we sought determine if component could regulate susceptibility In studies utilizing murine model,...
The disease severity of Entamoeba histolytica infection ranges from asymptomatic to life-threatening. Recent human and animal data implicate the gut microbiome as a modifier E. virulence. Here we have explored association with susceptibility amebiasis in infants mouse model amebic colitis. Dysbiosis occurred symptomatic children, evidenced by lower Shannon diversity index microbiota. To test if dysbiosis was cause susceptibility, wild type C57BL/6 mice (which are innately resistant...
Abstract Immune dysregulation is characteristic of the more severe stages SARS-CoV-2 infection. Understanding mechanisms by which immune system contributes to COVID-19 severity may open new avenues treatment. Here we report that elevated interleukin-13 (IL-13) was associated with need for mechanical ventilation in two independent patient cohorts. In addition, patients who acquired while prescribed Dupilumab had less disease. infected mice, IL-13 neutralization reduced death and disease...
As the global polio eradication initiative prepares to cease use of oral vaccine (OPV) in 2020, there is increasing interest understanding if vaccination provides non-specific immunity other infections so that consequences this transition can be effectively planned for and mitigated.Data were collected from infants an urban slum Bangladesh (Mirpur, Dhaka) as part performance rotavirus vaccines developing countries (PROVIDE) study. Following with trivalent (tOPV) at 6, 10, 14 weeks, randomly...
The microbiome provides resistance to infection. However, the underlying mechanisms are poorly understood. We demonstrate that colonization with intestinal bacterium Clostridium scindens protects from Entamoeba histolytica colitis via innate immunity. Introduction of C. into gut microbiota epigenetically altered and expanded bone marrow granulocyte-monocyte progenitors (GMPs) resulted in increased neutrophils subsequent challenge E. histolytica. alone was sufficient expand GMPs gnotobiotic...
ABSTRACT Amebiasis is an enteric infection caused by Entamoeba histolytica , with symptoms ranging in severity from asymptomatic colonization to dysentery. Humans the Q223R leptin receptor mutation have increased susceptibility amebiasis, but mechanism has been unclear. Using a mouse model expressing mutation, we tested impact of on innate immune response E. infection. The 223R resulted delayed clearance amebae cecum, as had previously observed. We found that neutrophil influx site was...
Metabolic products of the microbiota can alter hematopoiesis. However, contribution and site action bile acids is poorly understood. Here, we demonstrate that secondary acids, deoxycholic acid (DCA) lithocholic (LCA), increase bone marrow myelopoiesis. Treatment cells with DCA LCA preferentially expanded immunophenotypic functional colony-forming unit-granulocyte macrophage (CFU-GM) granulocyte-monocyte progenitors (GMPs). treatment sorted hematopoietic stem progenitor (HSPCs) increased...
Alterations in the gut microbiota have been proposed to modify development and maintenance of obesity its sequelae. Definition underlying mechanisms has lagged, although ability commensal microbes drive pathways involved inflammation metabolism generated compelling, testable hypotheses. We studied C57BL/6 mice from two vendors that differ their obesogenic response colonization by specific members having well-described roles regulating immune responses. confirmed presence robust differences...
ABSTRACT Intestinal segmented filamentous bacteria (SFB) protect from ameba infection, and protection is transferable with bone marrow dendritic cells (BMDCs). SFB cause an increase in serum amyloid A (SAA), suggesting that SAA might mediate SFB's effects on BMDCs. Here we further explored the role of SFB-mediated protection. Transient gut colonization or administration alone transiently increased H3K27 histone demethylase Jmjd3, persistently Csf2ra expression granulocyte monocyte precursors...
ABSTRACT Clostridium difficile is a major, life-threatening hospital-acquired pathogen that causes mild to severe colitis in infected individuals. The tissue destruction and inflammation which characterize C. infection (CDI) are primarily due the Rho-glucosylating toxins A B. These cause epithelial cell death induce robust inflammatory signaling by activating transcription factor NF-κB, leading chemokine cytokine secretion. also activate inflammasome complex, leads secretion of pyrogenic...
Amebiasis is a neglected tropical disease caused by Entamoeba histolytic a. Although the burden varies geographically, amebiasis estimated to account for some 55,000 deaths and millions of infections globally per year. Children travelers are among groups with greatest risk infection. There currently no licensed vaccines prevention amebiasis, although key immune correlates protection have been proposed from observational studies in humans. We previously described development liposomal...
The parasite Entamoeba histolytica is a cause of diarrhea in infants low-income countries. Previously, it was shown that tumor necrosis factor alpha (TNF-α) production associated with increased risk E. children. Interleukin-25 (IL-25) cytokine produced by intestinal epithelial cells has role maintenance gut barrier function and inhibition TNF-α production. IL-25 expression decreased humans the mouse model amebic colitis. Repletion blocked infection disruption mice, eosinophils, suppressed...
Entamoeba histolytica is a pathogenic protozoan parasite that causes intestinal colitis, diarrhea, and in some cases, liver abscess. Through transcriptomics analysis, we observed E. infection was associated with increased expression of IL-33 mRNA both the human murine colon. IL-33, IL-1 family cytokine, released after cell injury to alert immune system tissue damage. Treatment recombinant protected mice from amebic damage; moreover, blocking signaling made more susceptible amebiasis. limited...
Amixicile shows efficacy in the treatment of Clostridium difficile infections (CDI) a mouse model, with no recurrence CDI. Since amixicile selectively inhibits action B vitamin (thiamine pyrophosphate) cofactor pyruvate:ferredoxin oxidoreductase (PFOR), it may both escape mutation-based drug resistance and spare beneficial probiotic gut bacteria that do not express this enzyme. is water-soluble derivative nitazoxanide (NTZ), an antiparasitic therapeutic also against CDI humans. In...
Giardia lamblia is a common intestinal parasitic infection that although often acutely asymptomatic, associated with debilitating chronic and extra-intestinal sequelae. In previously healthy adults, primary sporadic can lead to gut dysfunction fatigue. These symptoms correlate markers of inflammation persist well after the cleared. contrast, in endemic settings, first exposure occurs children who are frequently malnourished also co-infected other enteropathogens. these children, rarely...
BackgroundEnvironmental factors that influence wheezing in early childhood the developing world are not well understood and may be useful predicting respiratory outcomes. Therefore, our objective was to determine can predict wheezing.MethodsChildren from Dhaka, Bangladesh were recruited at birth episodes of measured alongside nutritional, immunological socioeconomic over a one-year period. Poisson Regression with variable selection utilized what associated wheezing.ResultsElevated serum...
Abstract/Summary Murine models of SARS-CoV-2 infection are critical for elucidating the biological pathways underlying COVID-19 disease. Because human ACE2 is receptor SARS-CoV-2, mice expressing gene have shown promise as a potential model COVID-19. Five from transgenic mouse strain K18- hACE2 were intranasally inoculated with Hong Kong/VM20001061/2020. Mice followed twice daily five days and scored weight loss clinical symptoms. Infected did not exhibit any signs until day four, when loss,...
The intestinal surface is directly exposed to both commensal microorganisms as well pathogens with a single layer of epithelium separating luminal from internal tissues. Antimicrobial peptides play crucial role in allowing epithelial cells contain the lumen beneficial and pathogenic microorganisms. dependent, produced, Th2 cytokine IL-25 can induce IL-13 potentially antimicrobial peptide angiogenin-4. Here we show that downstream required mediated induction angiogenin-4 furthermore not...
ABSTRACT Diarrheal diseases with infectious etiology remain a major cause of death globally, particularly in low-income countries. Entamoeba histolytica is pathogenic protozoan parasite that the causative agent amebiasis. Amebiasis has wide presentation clinical severity many factors, including bacterial microbiota, contributing to this variation. The innate immune response also plays critical role regulating E. infection, neutrophils reported have protective role. Despite this, precise...