A5077087163- Immune Response and Inflammation
- interferon and immune responses
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Listeria monocytogenes in Food Safety
- MicroRNA in disease regulation
- Essential Oils and Antimicrobial Activity
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Salmonella and Campylobacter epidemiology
- Hepatitis C virus research
- T-cell and B-cell Immunology
- IL-33, ST2, and ILC Pathways
- Inflammatory Bowel Disease
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Immunotherapy and Immune Responses
- Genomics, phytochemicals, and oxidative stress
- NF-κB Signaling Pathways
- Probiotics and Fermented Foods
- Respiratory viral infections research
- Systemic Lupus Erythematosus Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Natural product bioactivities and synthesis
- Escherichia coli research studies
University of Washington
2012-2024
Seattle University
2013-2021
Washington University in St. Louis
2019-2021
Frederick National Laboratory for Cancer Research
2010-2013
National Cancer Institute
2010-2011
Center for Cancer Research
2010-2011
Abstract Neutrophils are implicated in multiple homeostatic and pathological processes, but whether functional diversity requires discrete neutrophil subsets is not known. Here, we apply single-cell RNA sequencing to neutrophils from normal inflamed mouse tissues. Whereas conventional clustering yields alternative organizational structures, diffusion mapping plus velocity discloses a single developmental spectrum, ordered chronologically. Termed here neutrotime, this spectrum extends...
Synthetic oligonucleotides ( ODN ) expressing C p G motifs mimic the ability of bacterial DNA to trigger innate immune system via TLR 9. Plasmacytoid dendritic cells (p DC s) make a critical contribution ensuing response. This work examines induction antiviral IFN ‐β) and pro‐inflammatory IL ‐6) cytokines by ‐stimulated human s CAL ‐1 cell line. Results show that interferon regulatory factor‐5 IRF ‐5) NF ‐κ B p50 are key co‐regulators ‐β ‐6 expression following 9‐mediated activation s. The...
The oxidoreductase RECON is a high-affinity cytosolic sensor of bacterium-derived cyclic dinucleotides (CDNs). CDN binding inhibits RECON's enzymatic activity and subsequently promotes inflammation. In this study, we sought to characterize the effects on infection cycle intracellular bacterium Listeria monocytogenes, which secretes di-AMP (c-di-AMP) into cytosol infected host cells. Here, report that during RECON-deficient hepatocytes, exhibit hyperinflammatory responses, L. monocytogenes...
Summary Advances in whole‐genome sequencing (WGS) technologies have documented genetic diversity and epidemiology of the major foodborne pathogen Listeria monocytogenes ( Lm ) Europe North America, but data concerning South America are scarce. Here, we examined population structure this collected Brazil. Based on core genome multilocus sequence typing (cgMLST), isolates from lineages I n = 22; 63%) II 13; 37%) were distributed into 10 different sublineages (SLs) represented 31 new cgMLST...
Background There have been conflicting reports of the role Type I interferons (IFN) in inflammatory bowel disease (IBD). Clinical trials shown potent efficacy systemic interferon-beta (IFN-β) inducing remission ulcerative colitis. Likewise, IFNAR1−/− mice display an increased sensitivity to dextran sulfate sodium (DSS)-induced colitis, suggesting IFN play a protective during inflammation gut. Curiously, however, there also detailing spontaneous development IBD patients receiving IFN-β...
Transposon sequencing (Tn-seq) is a powerful genome-wide technique to assess bacterial fitness under varying growth conditions. However, screening via Tn-seq in vivo challenging. Dose limitations and host restrictions create bottlenecks that diminish the transposon mutant pool being screened. Here, we have developed murine model with disruption Akr1c13 renders resulting RECON-/- mouse resistant high-dose infection. We leveraged this perform screen of human pathogen Listeria monocytogenes...
Pathogens encounter numerous antimicrobial responses during infection, including the reactive oxygen species (ROS) burst. ROS-mediated oxidation of host membrane poly-unsaturated fatty acids (PUFAs) generates toxic alpha-beta carbonyl 4-hydroxy-2-nonenal (4-HNE). Although studied extensively in context sterile inflammation, research into 4-HNE's role infection remains limited. Here, we found that 4-HNE is generated bacterial it impacts growth and survival a range bacteria, intracellular...
Abstract Tight regulation of interferon-gamma (IFN-g) expression is critical for an optimal immune response. IFN-g mRNA levels are attenuated by AU-rich element (ARE)-mediated decay (AMD) via the tristetraprolin (TTP) complex. Here we show that miR-29 targets 3'untranslated region and unlike conventional inhibitory function miRNAs, increases protein stabilizing mRNA. Through analysis RNA structure derived chemoenzymatic probing, demonstrate AMD blocked a induced conformational switch makes...
Abstract Transposon sequencing (Tn-seq) is a powerful genome-wide technique to assess bacterial fitness under varying growth conditions. However, screening via Tn-seq in vivo challenging. Dose limitations and host restrictions create bottlenecks that diminish the transposon mutant pool being screened. Here we have developed murine model with disruption Akr1c13 renders resulting RECON -/- mouse resistant high dose infection. We leveraged this perform screen of human pathogen Listeria...
Abstract Host cells have evolved a sophisticated arsenal of germ-line encoded pattern recognition receptors that detect vast array microorganisms in distinct tissues and cellular compartments. Cytoplasmic sensors monitor for microbes gain access to the host cell cytosol following breach plasma membrane or intracellular invasion. This sensing is achieved through detection invariant molecular patterns associated with stress responses indicate presence pathogen. Cyclic dinucleotides (cdNs) both...
Abstract The goal of the proposed research is to determine how interferon regulatory factor 5(IRF5) lupus risk variant translates into biological systemic erythematosus (SLE). Genome wide association studies (GWAS) have identified IRF5 as one most strongly associated genes with susceptibility SLE. Although genetic clear, exact mechanism by which promotes for still unknown. We are investigating negative factors activity under normal conditions, unable regulate exon 6 variants thereby...
Abstract Hepatitis C virus (HCV) is a hepatotrophic ssRNA that infects over 160 million people worldwide and 60–80% of HCV cases will persist to chronic infection, serious risk factor for liver diseases. We recently discovered infection hepatocytes induces expression two microRNAs (miRNAs), miR-208b miR-499a-5p. found these miRNA are capable decreasing IFNL2 IFNL3 aid viral replication. Here we show miR-499a-5p block type I IFN signaling in HCV-infected by directly targeting down regulating...
Abstract Robust production of type I interferon (IFN) by plasmacytoid dendritic cells (pDCs) occurs in response to Toll-like receptor 9 (TLR9) activation unmethylated CpG dinucleotides present bacterial and viral DNA. Previous work using different oligodeoxynucleotides (ODN) revealed that CpG-A ODN but not CpG-B robustly induce IFN-α pDCs. Although do efficiently IFN-α, they are capable highly inducing IFN-β. However, it is currently unclear what factors mediate induction IFN-β human Using...
Abstract We have shown that leukemic T cells from anaplastic lymphoma kinase-positive large cell (ALK+ALCL) patients aberrantly express IL-22R1, the private receptor for IL-22, on their surface. This causes these to resemble a Th17 inflammatory type. The expression of IL-22R1 leads IL-22 production, which then feeds back in an autocrine manner. signaling also stimulates IL-17 results damaging systemic inflammation, common complication seen ALK+ALCL patients. may be potential prognostic...