- Viral gastroenteritis research and epidemiology
- CRISPR and Genetic Engineering
- Viral Infections and Immunology Research
- Animal Virus Infections Studies
- RNA and protein synthesis mechanisms
- Virus-based gene therapy research
- Bacterial Genetics and Biotechnology
- Mycobacterium research and diagnosis
- Insect symbiosis and bacterial influences
- Gut microbiota and health
- Bacteriophages and microbial interactions
- Cytokine Signaling Pathways and Interactions
- Clostridium difficile and Clostridium perfringens research
- Reproductive Physiology in Livestock
- Microbial Community Ecology and Physiology
- Hematopoietic Stem Cell Transplantation
- Immune Response and Inflammation
- Neutropenia and Cancer Infections
- Reproductive System and Pregnancy
- SARS-CoV-2 and COVID-19 Research
- Diabetes and associated disorders
- Reproductive tract infections research
- Advanced Thermodynamic Systems and Engines
- Immune Cell Function and Interaction
Washington University in St. Louis
2019-2024
University of Alabama
2016-2024
University of Virginia
2023
Staphylococci are prevalent skin-dwelling bacteria that also leading causes of antibiotic-resistant infections. Viruses infect and lyse these organisms (virulent staphylococcal phages) can be used as alternatives to conventional antibiotics represent promising tools eliminate or manipulate specific species in the microbiome. However, since over half their genes have unknown functions, virulent phages carry inherent risk cause downstream side effects. Further, swift destructive reproductive...
Murine norovirus (MNoV) is an important model of human (HNoV) and mucosal virus infection more broadly. Viral receptor utilization a major determinant cell tropism, host range, pathogenesis. The bona fide for HNoV unknown. Recently, we identified CD300lf as proteinaceous MNoV. Interestingly, its paralogue CD300ld was also sufficient MNoV in vitro. Here explored whether the sole physiologic vivo can use CD300 ortholog entry receptor. We report that both are by diverse strains further...
Abstract Antibiotic therapy, especially when administered long term, is associated with adverse hematologic effects such as cytopenia. Signals from the intestinal microbiota are critical to maintain normal hematopoiesis, and antibiotics can cause bone marrow suppression through depletion of microbiota. We reported previously that STAT1 signaling necessary for microbiota-dependent but precise mechanisms by which gut signals host regulate hematopoiesis remain undefined. sought identify cell...
CRISPR–Cas (Clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) is a prokaryotic immune system that destroys foreign nucleic acids in sequence-specific manner using Cas nucleases guided by RNAs (crRNAs). Staphylococcus epidermidis harbours Type III-A encodes the Cas10–Csm interference complex and crRNAs are subjected to multiple processing steps. The final step, called maturation, involves concerted effort between Csm3, ruler protein measures six-nucleotide...
CRISPR-Cas systems are a class of adaptive immune in prokaryotes that use small CRISPR RNAs (crRNAs) conjunction with CRISPR-associated (Cas) nucleases to recognize and degrade foreign nucleic acids. Recent studies have revealed Type III synthesize second messenger molecules previously unknown exist prokaryotes, cyclic oligoadenylates (cOA). These activate the Csm6 nuclease promote RNA degradation may also coordinate additional cellular responses Although cOA production has been...
As our understanding of the importance human microbiota in health and disease grows, so does need to carefully resolve delineate its genomic content. 16S rRNA gene-based analyses yield important insights into taxonomic composition, metagenomics-based approaches reveal functional potential microbial communities. However, these methods generally fail directly link genetic features, including bacterial genes mobile elements, each other their source genomes. Further, they are inadequate capture...
Interferons (IFNs) are key controllers of viral replication, with intact IFN responses suppressing virus growth and spread. Using the murine norovirus (MNoV) system, we show that IFNs exert selective pressure to limit pathogenic evolutionary potential this enteric virus. In animals lacking type I signaling, nonlethal MNoV strain CR6 rapidly acquired enhanced virulence via conversion a single nucleotide. This nucleotide change resulted in amino acid substitution F514I capsid, which led...
CRISPR-Cas is a prokaryotic adaptive immune system that prevents uptake of mobile genetic elements such as bacteriophages and plasmids. Plasmid transfer between bacteria particular clinical concern due to increasing amounts antibiotic resistant pathogens found in humans result resistance plasmids within species. Testing the ability systems block plasmid various conditions or with mutants provides key insights into functionality mechanisms well how spreads bacterial communities. Here, we...
Abstract Noroviruses (NoVs) are a leading cause of viral gastroenteritis. Despite global clinical relevance, our understanding how host factors, such as antiviral cytokines interferons (IFNs), modulate NoV population dynamics is limited. Murine (MNoV) tractable in vivo model for the study regulation NoV. A persistent strain MNoV, CR6, establishes reservoir intestinal tuft cells chronic shedding stool. However, influence innate immunity and permissive cell numbers on an open question. We...
Noroviruses (NoVs) are a leading cause of viral gastroenteritis. Despite global clinical relevance, our understanding how host factors, such as antiviral cytokines interferons (IFNs), modulate NoV population dynamics is limited. Murine (MNoV) tractable in vivo model for the study regulation NoV. A persistent strain MNoV, CR6, establishes reservoir intestinal tuft cells chronic shedding stool. However, influence innate immunity and permissive cell numbers on an open question. We generated...
Clustered regularly-interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins protect bacteria archaea from their viruses, anti-CRISPRs (Acrs) are small virus-encoded that inhibit CRISPR-Cas immunity. Over 80 families of Acrs have been described to date; however, only three these subvert Type III systems employ a complex network Cas accessory nucleases degrade viral nucleic acids. Here, we discover characterize AcrIIIA1, the first III-A specific anti-CRISPR...
Abstract Murine norovirus (MNoV) is an important model of human (HNoV) and mucosal virus infection more broadly. Viral receptor utilization a major determinant cell tropism, host range, pathogenesis. The bona fide for HNoV unknown. Recently, we identified CD300lf as proteinaceous MNoV. Interestingly, its paralogue CD300ld was also sufficient MNoV in vitro . Here explored whether the sole physiologic vivo can use CD300 ortholog entry receptor. We report that both are by diverse strains...