ORCID Profile
0000-0003-4035-6047
Current Organisation
Mater Research Institute The University of Queensland
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Publisher: Informa UK Limited
Date: 19-12-2014
DOI: 10.3109/00365521.2014.966321
Abstract: The innate immune system is a key factor in understanding the pathogenesis of inflammatory bowel disease (IBD) and in the hopes of improving its treatment. NOD2, a pattern recognition receptor, was one of the first major susceptibility genes identified in Crohn's disease (CD). This discovery has been followed by genome-wide association studies that have identified other genes involved in innate immune responses. Most notably, polymorphisms in the interleukin (IL)-23 receptor have also been linked to IBD - both CD and ulcerative colitis. At the core of the innate immune defects associated with IBD is a lack of generating a robust response to control invasive commensal or pathogenic bacteria. The defect sometimes lies in a failure of the epithelium to express antimicrobial peptides or in defective control of intracellular bacteria by phagocytic cells such as dendritic cells, macrophages, or neutrophils. The recent identification of innate lymphoid cells that express the IL-23 receptor and generate both proinflammatory and protective or regulatory responses to commensal or pathogenic bacteria provides another layer of complexity to the interplay of host protection and dysregulated inflammation. Although inhibition of tumor necrosis factor has been highly successful as a strategy in treating IBD, we must better understand the nuanced role of other innate cytokines before we may incorporate these in the treatment of IBD.
Publisher: Elsevier BV
Date: 2018
Publisher: Oxford University Press (OUP)
Date: 22-08-2022
DOI: 10.1093/IBD/IZAC151
Abstract: Inflammatory bowel disease (IBD) involves chronic T cell–mediated inflammatory responses. Vedolizumab (VDZ), a monoclonal antibody against α4β7 integrin, inhibits lymphocyte extravasation into intestinal mucosae and is effective in ulcerative colitis (UC) and Crohn’s disease (CD). We sought to identify immune cell phenotypic and gene expression signatures that related to response to VDZ. Peripheral blood (PBMC) and lamina propria mononuclear cells (LPMCs) were analyzed by flow cytometry and Cytofkit. Sorted CD4 + memory (Tmem) or regulatory T (Treg) cells from PBMC and LPMC were analyzed by RNA sequencing (RNA-seq). Clinical response (≥2-point drop in partial Mayo scores [UC] or Harvey-Bradshaw index [CD]) was assessed 14 to 22 weeks after VDZ initiation. Machine-learning models were used to infer combinatorial traits that predicted response to VDZ. Seventy-one patients were enrolled: 37 received VDZ and 21 patients remained on VDZ & years. Fourteen of 37 patients (38% 8 UC, 6 CD) responded to VDZ. Immune cell phenotypes and CD4 + Tmem and Treg transcriptional behaviors were most ergent between the ileum and colon, irrespective of IBD subtype or inflammation status. Vedolizumab treatment had the greatest impact on Treg metabolic pathways, and response was associated with increased expression of genes involved in oxidative phosphorylation. The strongest clinical predictor of VDZ efficacy was concurrent use of thiopurines. Mucosal tissues offered the greatest number of response-predictive biomarkers, whereas PBMC Treg-expressed genes were the best predictors in combinatorial models of response. Mucosal and peripheral blood immune cell phenotypes and transcriptional profiles can inform VDZ efficacy and inform new opportunities for combination therapies.
Publisher: Wiley
Date: 16-01-2023
DOI: 10.1111/JGH.16102
Abstract: Prevention of liver failure arising from accidental or deliberate paracetamol (acetaminophen [APAP]) overdose remains a vexed health problem despite well‐publicized guidelines for its early detection and treatment. It is recognized that the gut may aggravate liver pathology, via the gut–liver axis. The main aim of this study was to assess the role of the colon in APAP‐induced liver toxicity. Liver necrosis and colitis were studied following sublethal doses of APAP administered intraperitoneally to C57Bl/6 wild‐type (WT) mice, as well as to C57Bl/6 Winnie mice, which develop a spontaneous colitis caused by a SNP in Muc2 , and WT mice with acute DSS‐induced colitis. Repeated APAP exposure was studied in WT and Rag1 ko mice that lack mature T and B lymphocytes. APAP overdose resulted in significant colonic injury in WT mice ( P 0.05), which resolved by 24 h. Underlying colitis was not associated with liver necrosis, but colitis exacerbated APAP‐induced liver injury and extended APAP‐colonic injury. Prior APAP exposure exacerbated both APAP‐liver and APAP‐colonic injury more so in WT than Rag1 ko mice. APAP impaired barrier function with increased intestinal permeability and associated bacterial translocation to the liver and spleen in mice with the Winnie phenotype. This study identifies novel roles for APAP in causing colitis, the lification of APAP‐liver toxicity where there is underlying colitis, and involvement of immune memory in APAP‐toxicity. The latter could be key for decoding the poorly understood but important clinical entity of chronic APAP liver failure.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Wiley
Date: 04-08-2009
Publisher: Public Library of Science (PLoS)
Date: 03-12-2014
Publisher: MDPI AG
Date: 10-12-2020
DOI: 10.3390/V12121424
Abstract: Viruses represent important test cases for data federation due to their genome size and the rapid increase in sequence data in publicly available databases. However, some consequences of previously decentralized (unfederated) data are lack of consensus or comparisons between feature annotations. Unifying or displaying alternative annotations should be a priority both for communities with robust entry representation and for nascent communities with burgeoning data sources. To this end, during this three-day continuation of the Virus Hunting Toolkit codeathon series (VHT-2), a new integrated and federated viral index was elaborated. This Federated Index of Viral Experiments (FIVE) integrates pre-existing and novel functional and taxonomy annotations and virus–host pairings. Variability in the context of viral genomic ersity is often overlooked in virus databases. As a proof-of-concept, FIVE was the first attempt to include viral genome variation for HIV, the most well-studied human pathogen, through viral genome ersity graphs. As per the publication of this manuscript, FIVE is the first implementation of a virus-specific federated index of such scope. FIVE is coded in BigQuery for optimal access of large quantities of data and is publicly accessible. Many projects of database or index federation fail to provide easier alternatives to access or query information. To this end, a Python API query system was developed to enhance the accessibility of FIVE.
Publisher: Springer Science and Business Media LLC
Date: 27-04-2020
DOI: 10.1038/S41467-020-15817-5
Abstract: The endothelial cell adhesion molecule E-selectin is a key component of the bone marrow hematopoietic stem cell (HSC) vascular niche regulating balance between HSC self-renewal and commitment. We now report in contrast, E-selectin directly triggers signaling pathways that promote malignant cell survival and regeneration. Using acute myeloid leukemia (AML) mouse models, we show AML blasts release inflammatory mediators that upregulate endothelial niche E-selectin expression. Alterations in cell-surface glycosylation associated with oncogenesis enhances AML blast binding to E-selectin and enable promotion of pro-survival signaling through AKT/NF-κB pathways. In vivo AML blasts with highest E-selectin binding potential are 12-fold more likely to survive chemotherapy and main contributors to disease relapse. Absence (in Sele −/− hosts) or therapeutic blockade of E-selectin using small molecule mimetic GMI-1271/Uproleselan effectively inhibits this niche-mediated pro-survival signaling, d ens AML blast regeneration, and strongly synergizes with chemotherapy, doubling the duration of mouse survival over chemotherapy alone, whilst protecting endogenous HSC.
Publisher: Wiley
Date: 10-06-2010
Publisher: Springer Science and Business Media LLC
Date: 28-04-2020
DOI: 10.1186/S13059-020-02014-2
Abstract: There is an increasing demand for accurate and fast metagenome classifiers that can not only identify bacteria, but all members of a microbial community. We used a recently developed concept in read mapping to develop a highly accurate metagenomic classification pipeline named CCMetagen. The pipeline substantially outperforms other commonly used software in identifying bacteria and fungi and can efficiently use the entire NCBI nucleotide collection as a reference to detect species with incomplete genome data from all biological kingdoms. CCMetagen is user-friendly, and the results can be easily integrated into microbial community analysis software for streamlined and automated microbiome studies.
Publisher: American Society for Cell Biology (ASCB)
Date: 30-10-2023
Publisher: Elsevier BV
Date: 2023
Publisher: Elsevier BV
Date: 2022
Publisher: Public Library of Science (PLoS)
Date: 28-09-2015
Publisher: Oxford University Press (OUP)
Date: 12-2020
DOI: 10.1093/BIOINFORMATICS/BTAA1027
Abstract: We present NCBI-taxonomist—a command-line tool written in Python that collects and manages taxonomic data from the National Center for Biotechnology Information (NCBI). NCBI-taxonomist does not depend on a pre-downloaded taxonomic database but can store data locally. NCBI-taxonomist has six commands to map, collect, extract, resolve, import and group taxonomic data that can be linked together to create powerful analytical pipelines. Because many lifescience databases use the same taxonomic information, the data managed by NCBI-taxonomist is not limited to NCBI and can be used to find data linked to taxonomic information present in other scientific databases. NCBI-taxonomist is implemented in Python 3 (≥3.8) and available at anpb/ncbi-taxonomist and via PyPi (roject/ncbi-taxonomist/), as a Docker container (anpb/ncbi-taxonomist/container_registry/) and Singularity (v3.5.3) image (cloud.sylabs.io/library/jpb/ncbi-taxonomist). NCBI-taxonomist is licensed under the GPLv3.
Publisher: Oxford University Press (OUP)
Date: 04-2016
Publisher: Elsevier BV
Date: 2020
Publisher: Cold Spring Harbor Laboratory
Date: 03-2022
DOI: 10.1101/2022.02.28.482397
Abstract: Despite a rapid expansion in the number of known RNA viruses following the advent of metagenomic sequencing, the identification and annotation of highly ergent RNA viruses remains challenging, particularly from poorly characterized hosts and environmental s les. Protein structures are more conserved than primary sequence data, such that structure-based comparisons provide an opportunity to reveal the viral “dusk matter”: viral sequences with low, but detectable, levels of sequence identity to known viruses with available protein structures. Here, we present a new open computational and resource – RdRp-scan – that contains a standardized bioinformatic toolkit to identify and annotate ergent RNA viruses in metagenomic sequence data based on the detection of RNA dependent RNA polymerase (RdRp) sequences. By combining RdRp-specific Hidden Markov models (HMM) and structural comparisons we show that RdRp-scan can efficiently detect RdRp sequences with identity levels as low as 10% to those from known viruses and not identifiable using standard sequence-to-sequence comparisons. In addition, to facilitate the annotation and placement of newly detected and ergent virus-like sequences into the known ersity of RNA viruses, RdRp-scan provides new custom and curated databases of viral RdRp sequences and core motif, as well as pre-built RdRp alignments. In parallel, our analysis of the sequence ersity detected by RdRp-scan revealed that while most of the taxonomically unassigned RdRps fell into pre-established clusters, some sequences cluster into potential new orders of RNA viruses related to the Wolframvirales and Tolivirales . Finally, a survey of the conserved A, B and C RdRp motifs within the RdRp-scan sequence database revealed additional variations of both sequence and position, which might provide new insights into the structure, function and evolution of viral RdRps.
Publisher: Wiley
Date: 09-03-2021
DOI: 10.1111/IMCB.12447
Abstract: The endothelial adhesion protein E‐selectin/CD62E is not required for leukocyte homing, unlike closely related family member P‐selectin/CD62P. As transmigration through the endothelium is one of the first steps in generating a local immune response, we hypothesized that E‐selectin may play additional roles in the early stages of immune activation. We found contact with E‐selectin, but not P‐selectin or vascular cell adhesion molecule 1 (CD106), induced phosphorylation of protein kinase B (AKT) and nuclear factor‐κB in mouse bone marrow‐derived macrophages (BMDMs) in vitro . This occurred within 15 min of E‐selectin contact and was dependent on phosphatidylinositol‐3 kinase activity. Binding to E‐selectin activated downstream proteins including mammalian target of rapamycin, p70 ribosomal protein S6 kinase and eukaryotic translation initiation factor 4E‐binding protein 1. Functionally, adhesion to E‐selectin induced upregulation of CD86 expression and CCL2 secretion. We next asked whether contact with E‐selectin impacts further BMDM stimulation. We found enhanced secretion of both interleukin (IL)‐10 and CCL2, but not tumor necrosis factor or IL‐6 in response to lipopolysaccharide (LPS) stimulation after adhesion to E‐selectin. Importantly, adhesion to E‐selectin did not polarize BMDMs to one type of response but enhanced both arginase activity and nitric oxide production following IL‐4 or LPS stimulation, respectively. In cultured human monocytes, adhesion to E‐selectin similarly induced phosphorylation of AKT. Finally, when E‐selectin was blocked in vivo in mice, thioglycollate‐elicited macrophages showed reduced CD86 expression, validating our in vitro studies. Our results imply functions for E‐selectin beyond homing and suggest that E‐selectin plays an early role in priming and lifying innate immune responses.
Publisher: Springer International Publishing
Date: 2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2015
Publisher: Elsevier BV
Date: 2020
Publisher: American Society of Hematology
Date: 07-02-2019
Publisher: Public Library of Science (PLoS)
Date: 14-05-2013
Publisher: Oxford University Press (OUP)
Date: 07-2020
DOI: 10.1093/VE/VEAA064
Abstract: The Flaviviridae family of positive-sense RNA viruses contains important pathogens of humans and other animals, including Zika virus, dengue virus, and hepatitis C virus. The Flaviviridae are currently ided into four genera—Hepacivirus, Pegivirus, Pestivirus, and Flavivirus—each with a erse host range. Members of the genus Hepacivirus are associated with an array of animal species, including humans, non-human primates, other mammalian species, as well as birds and fish, while the closely related pegiviruses have been identified in a variety of mammalian taxa, also including humans. Using a combination of total RNA and whole-genome sequencing we identified four novel hepaci-like viruses and one novel variant of a known hepacivirus in five species of Australian wildlife. The hosts infected comprised native Australian marsupials and birds, as well as a native gecko (Gehyra lauta). From these data we identified a distinct marsupial clade of hepaci-like viruses that also included an engorged Ixodes holocyclus tick collected while feeding on Australian long-nosed bandicoots (Perameles nasuta). Distinct lineages of hepaci-like viruses associated with geckos and birds were also identified. By mining the SRA database we similarly identified three new hepaci-like viruses from avian and primate hosts, as well as two novel pegi-like viruses associated with primates. The phylogenetic history of the hepaci- and pegi-like viruses as a whole, combined with co-phylogenetic analysis, provided support for virus-host co- ergence over the course of vertebrate evolution, although with frequent cross-species virus transmission. Overall, our work highlights the ersity of the Hepacivirus and Pegivirus genera as well as the uncertain phylogenetic distinction between.
Publisher: American Society for Microbiology
Date: 03-2016
DOI: 10.1128/IAI.01374-15
Abstract: Evidence obtained from gene knockout studies supports the role of Toll-like receptor 4 (TLR4) in intestinal inflammation and microbiota recognition. Increased epithelial TLR4 expression is observed in patients with inflammatory bowel disease. However, little is known of the effect of increased TLR4 signaling on intestinal homeostasis. Here, we examined the effect of increased TLR4 signaling on epithelial function and microbiota by using transgenic villin-TLR4 mice that overexpress TLR4 in the intestinal epithelium. Our results revealed that villin-TLR4 mice are characterized by increases in the density of mucosa-associated bacteria and bacterial translocation. Furthermore, increased epithelial TLR4 signaling was associated with an impaired epithelial barrier, altered expression of antimicrobial peptide genes, and altered epithelial cell differentiation. The composition of the colonic luminal and mucosa-associated microbiota differed between villin-TLR4 and wild-type (WT) littermates. Interestingly, WT mice cohoused with villin-TLR4 mice displayed greater susceptibility to acute colitis than singly housed WT mice did. The results of this study suggest that epithelial TLR4 expression shapes the microbiota and affects the functional properties of the epithelium. The changes in the microbiota induced by increased epithelial TLR4 signaling are transmissible and exacerbate dextran sodium sulfate-induced colitis. Together, our findings imply that host innate immune signaling can modulate intestinal bacteria and ultimately the host's susceptibility to colitis.
Publisher: Elsevier BV
Date: 2022
Location: Australia
No related grants have been discovered for Julie Davies.