A5025305464- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Multiple Sclerosis Research Studies
- Medical and Agricultural Research Studies
- Climate Change, Adaptation, Migration
- Migration, Aging, and Tourism Studies
- Viral-associated cancers and disorders
- T-cell and B-cell Immunology
- Reproductive System and Pregnancy
- Polyomavirus and related diseases
- Metabolism and Genetic Disorders
- Vitamin D Research Studies
- Epigenetics and DNA Methylation
- Diet and metabolism studies
- IL-33, ST2, and ILC Pathways
- Sepsis Diagnosis and Treatment
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Cytokine Signaling Pathways and Interactions
- Influenza Virus Research Studies
- Adrenal Hormones and Disorders
- Immune Response and Inflammation
- Metabolomics and Mass Spectrometry Studies
- Gut microbiota and health
- interferon and immune responses
- Plant Disease Resistance and Genetics
The University of Sydney
2015-2025
Westmead Institute for Medical Research
2016-2024
Westmead Hospital
2017
Nepean Hospital
2011-2016
Westmead Institute
2013
Millennium Institute
2013
WaterNSW
2012
To find and validate generalizable sepsis subtypes using data-driven clustering.We used advanced informatics techniques to pool data from 14 bacterial transcriptomic datasets eight different countries (n = 700).Retrospective analysis.Persons admitted the hospital with sepsis.None.A unified clustering analysis across discovery revealed three subtypes, which, based on functional analysis, we termed "Inflammopathic, Adaptive, Coagulopathic." We then validated these in nine independent five...
Improved risk stratification and prognosis prediction in sepsis is a critical unmet need. Clinical severity scores available assays such as blood lactate reflect global illness with suboptimal performance, do not specifically reveal the underlying dysregulation of sepsis. Here, we present prognostic models for 30-day mortality generated independently by three scientific groups using 12 discovery cohorts containing transcriptomic data collected from primarily community-onset patients....
Abstract Severe influenza infection has no effective treatment available. One of the key barriers to developing host-directed therapy is a lack reliable prognostic factors needed guide such therapy. Here, we use network analysis approach identify host associated with severe and fatal outcome. In patients moderate-to-severe diseases, uncover complex landscape immunological pathways, main changes occurring in pathways related circulating neutrophils. Patients disease display excessive...
Host response biomarkers can accurately distinguish between influenza and bacterial infection. However, published require the measurement of many genes, thereby making it difficult to implement them in clinical practice. This study aims identify a single-gene biomarker with high diagnostic accuracy equivalent multi-gene biomarkers. In this study, we combined an integrated genomic analysis 1071 individuals vitro experiments using well-established infection models. We identified biomarker,...
There is currently no reliable tool available to measure immune dysfunction in septic patients the clinical setting. This proof-of-concept study assesses potential of gene expression profiling whole blood as a monitor critically ill patients. Whole-blood samples were collected daily for up 5 days from admitted intensive care unit with sepsis. RNA isolated whole-blood was assayed on Illumina HT-12 microarrays consisting 48,804 probes. Microarray analysis identified 3,677 genes differentially...
Diagnosis of severe influenza pneumonia remains challenging because a lack correlation between the presence virus and clinical status. We conducted gene-expression profiling in whole blood critically ill patients to identify gene signature that would allow clinicians distinguish infection from other causes respiratory failure, such as bacterial pneumonia, noninfective systemic inflammatory response syndrome.Whole-blood samples were collected individuals assayed on Illumina HT-12 beadarrays....
Tissue mononuclear phagocytes (MNP) are specialised in pathogen detection and antigen presentation. As such they deliver HIV to its primary target cells; CD4 T cells. Most MNP transmission studies have focused on epithelial MNPs. However, as mucosal trauma inflammation now known be strongly associated with transmission, here we examine the role of sub-epithelial MNPs which present a diverse array subsets. We show that can penetrate surface interact resident anogenital explants define full...
Influenza A infection is a global disease that has been responsible for four pandemics over the last one hundred years. However, it remains poorly understood as to why some infected individuals succumb life threatening complications whilst others recover and are relatively unaffected. Using gene-expression analysis of circulating leukocytes, here we show progression towards severe influenza characterised by an abnormal transcriptional reprogramming cell cycle apoptosis pathways. In severely...
Abstract Transplacental immune regulation refers to the concept that during pregnancy, significant cross-talk occurs between maternal and fetal system with potential long-term effects for both mother child. In this study, we made surprising observation there is a strong correlation of peripheral blood regulatory T (Treg) cells fetus. contrast, no Treg cell paternal dyads (pairs), suggesting specific context rather than genetic parental similarity fetus, responsible correlation. Gene...
We have identified a marked over-representation of transcription factors controlling differentiation T, B, myeloid and NK cells among the 110 MS genes now known to be associated with multiple sclerosis (MS). To test if expression these might define molecular subtypes MS, we interrogated their in blood three independent cohorts untreated (from Sydney Adelaide) or clinically isolated syndrome (CIS, from San Francisco) patients. Expression (TF) T cell differentiation, EOMES, TBX21 other TFs was...
The vitamin D receptor (VDR) is a ligand-activated transcription factor that regulates gene expression in many cell types, including immune cells. It requires binding of 1,25 dihydroxy D3 (1,25D3) for activation. Many autoimmune diseases show latitude-dependent prevalence and/or association with deficiency, and supplementation commonly used their clinical management. 1,25D3 regulated by genes associated the risk predominantly expressed myeloid We determined VDR cistrome monocytes...
Objective Vaccination against hepatitis B virus (HBV) confers protection from subsequent infection through immunological memory that is traditionally considered the domain of adaptive immune system. This view has been challenged following identification antigen-specific natural killer cells (mNKs) in mice and non-human primates. While presence mNKs suggested humans based on expansion NK pathogen exposure, evidence regarding antigen-specificity lacking. Here, we demonstrate existence...
Genome wide association studies have identified > 200 susceptibility loci accounting for much of the heritability multiple sclerosis (MS). Epstein-Barr virus (EBV), a memory B cell tropic virus, has been as necessary but not sufficient development MS. The molecular and immunological basis this established. Infected proliferation is driven by signalling through EBV produced surface protein LMP1, homologue MS risk gene CD40. We investigated transcriptomes cells EBV-infected at Latency III...
Recent sero-epidemiological studies have strengthened the hypothesis that Epstein-Barr virus (EBV) may be a causal factor in multiple sclerosis (MS). Given complexity of EBV-host interaction, various mechanisms responsible for disease pathogenesis. Furthermore, it remains unclear whether this is disease-specific process. Here, we showed genes encoding EBV interactors are enriched loci associated with MS but not other diseases and prioritized therapeutic targets. Analyses blood brain...
Human genetic and animal studies have implicated the costimulatory molecule CD40 in development of multiple sclerosis (MS). We investigated cell specific gene protein expression variation controlled by variant(s) associated with MS, i.e. T-allele at rs1883832. Previously we had shown that risk allele is expressed a lower level whole blood, especially people MS. Here, defined immune subsets responsible for genotype disease effects on mRNA level. In which most highly expressed, B lymphocytes...
Metallothioneins (MTs) are small, cysteine-rich proteins characterized by a high affinity for monovalent and divalent cations, such as copper zinc. Of the four known MT isoforms, only, members of 1 2 subfamilies widely expressed, acting metal chaperones whose primary role is to mediate intracellular zinc homoeostasis. potently induced heavy metals other sources oxidative stress where they facilitate binding detoxification well free radical scavenging. Metallothionein expression documented in...
Epstein-Barr virus (EBV) infection may be necessary for the development of Multiple sclerosis (MS). Earlier we had identified six MS risk loci that are co-located with binding sites EBV transcription factor Nuclear Antigen 2 (EBNA2) in EBV-infected B cells (lymphoblastoid cell lines - LCLs).We used an allele-specific chromatin immunoprecipitation PCR assay to assess EBNA2 allelic preference. We treated LCLs a peptide inhibitor (EBNA2-TAT), reasoning inhibiting function would alter gene...
Genome-wide association studies have identified a linkage disequilibrium (LD) block on chromosome 12 associated with multiple sclerosis (MS), type 1 diabetes and other autoimmune diseases. This contains CYP27B1, which catalyzes the conversion of 25 vitamin D3 (VitD3) to 1,25VitD3. Fine-mapping analysis has failed identify 17 genes in this is most MS. We previously used functional approach causal gene. showed that expression several whole blood highly MS risk allele, but not CYP27B1. Here, we...
Abstract Translating the findings of genome wide association studies (GWAS) to new therapies requires identification relevant immunological contexts interrogate for genetic effects. In one largest GWAS, more than 200 risk loci have been identified Multiple Sclerosis (MS) susceptibility. Infection with Epstein-Barr virus (EBV) appears be necessary development (MS). Many MS are associated altered gene expression in EBV infected B cells (LCLs). We interrogated this context identify interaction...
Although the causes of Multiple Sclerosis (MS) still remain largely unknown, multiple lines evidence suggest that Epstein–Barr virus (EBV) infection may contribute to development MS. Here, we aimed identify potential contribution EBV-encoded and host cellular miRNAs MS pathogenesis. We identified differentially expressed in EBV infected B cells (LCLs) putative host/EBV miRNA interactions with risk loci. estimated genotype effect loci on miRNA:mRNA silico. found protective allele SNP...