Simon Lee Fellow; Interim Head, Centre for Personalised Medicine for Children; Program Head, Immunity and Inflammation; Team Leader, Systems Immunology
BSc (Hons) PhD Immunology & Genomics
Anthony Bosco was born and raised near Fremantle, Western Australia. He was awarded his PhD in 2007 from the University of Western Australia. He received Postdoctoral training at the Arizona Respiratory Centre and BIO5 Institute, The University of Arizona.
He leads a unique research program that is underpinned by the concept that genes do not exist nor function in isolation, they work together in networks. His lab employs network graph theory and computational systems biology to work backwards (reverse engineering) from genomic profiles of immune responses to reconstruct the wiring diagram of the underlying gene networks.
The long-term goal of this work is to unlock the basic mechanisms and principles that govern the functionality of the immune system in healthy versus diseased states, unveiling actionable targets for therapeutic intervention.
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Projects
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Publications
January 2021
Fine-Tuning the Tumour Microenvironment: Current Perspectives on the Mechanisms of Tumour Immunosuppression
Immunotherapy has revolutionised the treatment of cancers by harnessing the power of the immune system to eradicate malignant tissue. However, it is well recognised that some cancers are highly resistant to these therapies, which is in part attributed to the immunosuppressive landscape of the tumour microenvironment (TME). The contexture of the TME is highly heterogeneous and contains a complex architecture of immune, stromal, vascular and tumour cells in addition to acellular components such as the extracellular matrix. While understanding the dynamics of the TME has been instrumental in predicting durable responses to immunotherapy and developing new treatment strategies, recent evidence challenges the fundamental paradigms of how tumours can effectively subvert immunosurveillance. Here, we discuss the various immunosuppressive features of the TME and how fine-tuning these mechanisms, rather than ablating them completely, may result in a more comprehensive and balanced anti-tumour response.
Children's Cancers Published research Systems Immunology Subsite: CancerApril 2021Unlocking immune-mediated disease mechanisms with transcriptomics
The transcriptome represents the entire set of RNA transcripts expressed in a cell, reflecting both the underlying genetic and epigenetic landscape and environmental influences, providing a comprehensive view of functional cellular states at any given time. Recent technological advances now enable the study of the transcriptome at the resolution of individual cells, providing exciting opportunities to characterise cellular and molecular events that underpin immune-medicated diseases.
Published research Systems ImmunologyJuly 2021Small nucleolar RNA networks are up-regulated during human anaphylaxis
Anaphylaxis is a severe, potentially life-threatening allergic reaction driven primarily by the activation of mast cells. We still fail to understand factors underlying reaction severity. Furthermore, there is currently no reliable diagnostic test to confirm anaphylaxis in the emergency department.
Published research Systems Immunology Subsite: CancerJuly 2021IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming
High risk for virus-induced asthma exacerbations in children is associated with an IRF7lo immunophenotype, but the underlying mechanisms are unclear. Here, we applied a Systems Biology approach to an animal model comprising rat strains manifesting high versus low susceptibility to experimental asthma, induced by virus/allergen coexposure, to elucidate the mechanism(s)-of-action of the high-risk asthma immunophenotype.
Asthma Published research Experimental Immunology Inflammation Human Immunology Systems Immunology Respiratory Environmental HealthDecember 2020Transplacental Innate Immune Training via Maternal Microbial Exposure: Role of XBP1-ERN1 Axis in Dendritic Cell Precursor Programming
We recently reported that offspring of mice treated during pregnancy with the microbial-derived immunomodulator OM-85 manifest striking resistance to allergic airways inflammation, and localized the potential treatment target to fetal conventional dendritic cell (cDC) progenitors. Here, we profile maternal OM-85 treatment-associated transcriptomic signatures in fetal bone marrow, and identify a series of immunometabolic pathways which provide essential metabolites for accelerated myelopoiesis.
Published research Experimental Immunology Human Immunology Systems ImmunologySeptember 2020Decoding Susceptibility to Respiratory Viral Infections and Asthma Inception in Children
Human Respiratory Syncytial Virus and Human Rhinovirus are the most frequent cause of respiratory tract infections in infants and children and are major triggers of acute viral bronchiolitis, wheezing and asthma exacerbations.
Asthma Published research Early Childhood Development Systems Immunology Youth HealthJune 2020Assessing the unified airway hypothesis in children via transcriptional profiling of the airway epithelium
Upper and lower airways are conserved in their transcriptional composition, and variations associated with disease are present in both nasal and tracheal epithelium
Published research Systems Immunology Computational Biology Airway Epithelial Research P4 Respiratory Health for KidsMay 2020Bilateral murine tumor models for characterizing the response to immune checkpoint blockade
This protocol describes bilateral murine tumor models that display a symmetrical yet dichotomous response to immune checkpoint blockade
Children's Cancers Published research Systems Immunology Computational Biology Sarcoma Translational ResearchMay 2020Airway Epithelial Cell Immunity Is Delayed During Rhinovirus Infection in Asthma and COPD
We propose that propensity for viral exacerbations of asthma and COPD relate to delayed expression of epithelial cell innate anti-viral immune genes
Asthma Published research Systems ImmunologyFebruary 2020Network using Michaelis–Menten kinetics: constructing an algorithm to find target genes from expression data
We derived a simple ordinary differential equation-based model using Michaelis–Menten Kinetics to process the microarray data
Published research Systems ImmunologyJanuary 2019CD8+XCR1neg Dendritic Cells Express High Levels of Toll-Like Receptor 5 and a Unique Complement of Endocytic Receptors
Our data demonstrate that CD8+XCR1neg DCs possess a unique pattern of endocytic receptors and a restricted TLR profile that is particularly enriched for TLR5
Children's Cancers Published research Systems Immunology Cancer ImmunotherapyMarch 2019Upper Airway Cell Transcriptomics Identify a Major New Immunological Phenotype with Strong Clinical Correlates in Young Children with Acute Wheezing
Asthma exacerbations in children can be divided into IRF7hi versus IRF7lo phenotypes with associated differences in clinical phenotypes
Asthma Published research Systems ImmunologyJune 2019Very Early Identification and Intervention for Infants at Risk of Neurodevelopmental Disorders: A Transdiagnostic Approach
In this article, we examine the utility of a transdiagnostic, dimensional approach to very early identification and intervention for infants at risk of neurodevelopmental disorders
Published research Child Disability Autism Research Systems Immunology Youth Mental HealthJune 2019Personalized transcriptomics reveals heterogeneous immunophenotypes in children with viral bronchiolitis
Dysregulated expression of IFN-dependent pathways after respiratory viral infections is a defining immunophenotypic feature of AVB-susceptible infants
Published research Bronchiolitis Experimental Immunology Human Immunology Systems ImmunologyJuly 2019Sensitization to immune checkpoint blockade through activation of a STAT1/NK axis in the tumor microenvironment
Our results identify a pretreatment tumor microenvironment that predicts response to immune checkpoint blockade, which can be therapeutically attained
Children's Cancers Published research Systems Immunology Computational Biology Sarcoma Translational ResearchAugust 2019Innate immune activation occurs in acute food protein–induced enterocolitis syndrome reactions
Food reactions in food protein–induced enterocolitis syndrome are predominantly underpinned by activation of the innate immune system
Published research Systems Immunology Food AllergySeptember 2019Progressive increase of FcεRI expression across several PBMC subsets is associated with atopy and atopic asthma within school-aged children
The expression pattern of FcεRI on DC and basophils differentiates asthmatic from non-asthmatic atopic children
Asthma Published research Academic Biostatistics Experimental Immunology Human Immunology Systems ImmunologyNovember 2019Immunoinflammatory responses to febrile lower respiratory infections in infants display uniquely complex/intense transcriptomic profiles
the association between infant LRTI and risk for persistent wheeze/asthma in this cohort is generally stronger for fLRTIs than for other infection categories
Published research Experimental Immunology Human Immunology Systems ImmunologyDecember 2019QuantSeq. 3′ Sequencing combined with Salmon provides a fast, reliable approach for high throughput RNA expression analysis
QuantSeq, coupled with a fast quantification method such as Salmon, should provide a viable alternative to traditional RNA-Seq in many applications
Published research Systems ImmunologyDecember 2018Insights into respiratory disease through bioinformatics
Here, we review the basic concepts in bioinformatics and genomic data analysis and illustrate the application of these tools to further our understanding of lung diseases
Asthma Published research Systems ImmunologyNovember 2018Basophil counts in PBMC populations during childhood acute wheeze/asthma are associated with future exacerbations
Our findings suggest that the proportion of degranulated basophils can also be associated with recurrent exacerbations
Asthma Published research Experimental Immunology Human Immunology Systems ImmunologyAugust 2018Atopy-dependent and independent immune responses in the heightened severity of atopics to respiratory viral infections: Rat model studies
The co-exposure responses in the Th2high BN incorporated type I interferon/Th1, alternative macrophage activation/Th2 and Th17 signatures
Published research Experimental Immunology Human Immunology Systems ImmunologyJanuary 2018Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics
Our findings provide new insight into the molecular mechanisms operative at baseline in the airway mucosa in atopic asthmatic with natural aeroallergen exposure
Asthma Published research Human Immunology Systems Immunology Airway Epithelial Research Children's Lung Health P4 Respiratory Health for KidsApril 2017Dynamic versus static biomarkers in cancer immune checkpoint blockade: unravelling complexity
There has been a coordinated effort from academic institutions and the PI to identify biomarkers that can predict immune checkpoint blockade response in cancer.
Published research Vaccine Trials GroupMay 2017Protection against maternal infection-associated fetal growth restriction: Proof-of-concept with a microbial-derived immunomodulator
This study suggests that broad-spectrum protection-of-pregnancy against infection-associated inflammatory stress represents an achievable therapeutic goal
Published research Experimental Immunology Human Immunology Systems ImmunologyJuly 2017CFTR-dependent defect in alternatively-activated macrophages in cystic fibrosis
CFTR-dependent imbalance of macrophage phenotypes and functions could contribute to the exaggerated inflammatory response seen in CF lung disease
Cystic Fibrosis Published research Human Immunology Systems ImmunologyAugust 2017Epigenome-wide analysis links SMAD3 methylation at birth to asthma in children of asthmatic mothers
We sought to assess whether the trajectory to asthma begins already at birth and whether epigenetic mechanisms, contribute to asthma inception.
Asthma Published research Inflammation Human ImmunologyOctober 2017Critical role of plasmacytoid dendritic cells in regulating gene expression and innate immune responses to human rhinovirus-16
Though HRVs are usually innocuous viruses, they can trigger serious consequences in certain individuals, especially in the setting of IFN synthesis.
Published research InflammationNovember 2017A genome-by-environment interaction classifier for precision medicine: personal transcriptome response to rhinovirus identifies children prone to asthma exacerbations
To introduce a disease prognosis framework enabled by a robust classification scheme derived from patient-specific transcriptomic response to stimulation.
Asthma Published research Systems ImmunologyNovember 2017Airway IRF7hi versus IRF7lo molecular response patterns determine clinical phenotypes in children with acute wheezing
We employed a systems biology approach to delineate upper airway gene network patterns underlying asthma exacerbation phenotypes in children.
Published research Systems ImmunologyNovember 2016Respiratory viral infections and host responses; insights from genomics
Review of the viral sensing pathways and organizing principles that govern the innate immune response to infection
Published research Systems ImmunologyOctober 2016Effect of human rhinovirus infection on airway epithelium tight junction protein disassembly and transepithelial permeability
HRV-1B infection directly alters human airway epithelial TJ expression leading to increased epithelial permeability potentially via antiviral response of IL-15
Published research Systems Immunology Airway Epithelial Research P4 Respiratory Health for Kids Respiratory Environmental HealthSeptember 2016Identification of genes differentially regulated by vitamin D deficiency that alter lung pathophysiology and inflammation in allergic airways disease
Vitamin D deficiency exacerbates house dust mite-induced inflammation and alterations in lung structure and function
Asthma Published research Inflammation Systems Immunology Cardiometabolic Sunhealth Airway Epithelial ResearchFebruary 2016Rapid recruitment of CD14+ monocytes in experimentally induced allergic rhinitis in human subjects
Mononuclear phagocyte population is directly involved in the production of proinflammatory chemokines that attract other immune cells
Published research Systems ImmunologyJanuary 2016Interferon regulatory factor 7 regulates airway epithelial cell responses to human rhinovirus infection
IRF7 regulates the expression of genes involved in antiviral immunity, inflammation, and the response to oxidative stress during HRV infections in HBE cells
Published research Systems ImmunologyJanuary 2016Rhinovirus-induced asthma exacerbations and risk populations
Asthma exacerbations are heterogeneous conditions that involve the complex interplay between environmental exposures and innate and adaptive immune function
Asthma Published research Systems ImmunologyJanuary 2016Distinguishing benign from pathologic TH2 immunity in atopic children
In addition to its role in blocking TH2 effector activation in the late-phase allergic response, IL-10 is a known IgG1 switch factor
Asthma Published research Allergy & Infectious Diseases Experimental Immunology Human Immunology Systems ImmunologyJanuary 2016Differential gene network analysis for the identification of asthma-associated therapeutic targets in allergen-specific T-helper memory responses
Differential network analysis of allergen-induced CD4 T cell responses can unmask covert disease-associated genes and pin point novel therapeutic targets
Asthma Published research Human Immunology Systems ImmunologyJune 2015Towards a PBMC "virogram assay" for precision medicine: Concordance between ex vivo and in vivo viral infection transcriptomes
In this rhinovirus study, we first hypothesized that ex vivo human cells response to virus can serve as a proxy for otherwise controversial in vivo human...
Published research Infectious Diseases Systems ImmunologyJanuary 2015Network analysis of immunotherapy-induced regressing tumours identifies novel synergistic drug combinations
Cancer immunotherapy has shown impressive results, but most patients do not respond.
Children's Cancers Published research Systems ImmunologyMarch 2015The effects of in utero vitamin D deficiency on airway smooth muscle mass and lung function
In this study, we aimed to uncover the molecular mechanisms contributing to altered lung structure and function.
Published research Vitamin D and Sunlight Inflammation Systems Immunology Cardiometabolic SunhealthJuly 2014Genomic responses during acute human anaphylaxis are characterized by upregulation of innate inflammatory gene networks
The aim of this study was to examine the gene response of white blood cells in severe allergic reactions to identify genes that could be targets to new drugs...
Published research Systems ImmunologyMarch 2014Comment on "Drug discovery: Turning the titanic"
We propose that the molecular and cellular events that govern a resolving, rather than an evolving, disease may reveal new druggable pathways.
Published research Systems ImmunologyJanuary 2014Intracellular growth of Mycobacterium avium subspecies and global transcriptional responses in human macrophages after infection
Mycobacterium avium subsp. avium (Maa) and M. avium subsp. hominissuis (Mah) are environmental mycobacteria and significant opportunistic pathogens.
Published research Systems ImmunologyFebruary 2013In utero exposure to arsenic alters lung development and genes related to immune and mucociliary function in mice
In utero exposure to arsenic via drinking water increases the risk of lower respiratory tract infections during infancy and mortality from bronchiectasis in...
Published research Systems Immunology Respiratory Environmental HealthFebruary 2012A genomics-based approach to assessment of vaccine safety and immunogenicity in children
This methodology has significant potential to identify covert interactions between inflammatory pathways triggered by vaccination, and as such may be a...
Published research Immunisation Human Immunology Systems Immunology Vaccine Trials GroupFebruary 2012T-cell activation genes differentially expressed at birth in CD4+ T-cells from children who develop IgE food allergy
To show underlying mechanisms, we examined differences in T-cell gene expression in samples at birth and at 1 year in children with and without IgE allergy.
Published research Child Allergy & Immunology Human Immunology Systems Immunology ORIGINS Food AllergyJanuary 2012Interferon regulatory factor 7 is a major hub connecting interferon-mediated responses in virus-induced asthma exacerbations in vivo
The objective of this study was to elucidate the molecular networks that underpin virus-induced exacerbations in asthmatic children in vivo.
Asthma Published research Systems ImmunologyJanuary 2012Interferon regulatory factor 7 is a major hub connecting interferon-mediated responses in virus-induced asthma exacerbations in vivo
The objective of this study was to elucidate the molecular networks that underpin virus-induced exacerbations in asthmatic children in vivo.
Asthma Published research Systems ImmunologyJanuary 2012Airway Epithelial Cells Condition Dendritic Cells to Express Multiple Immune Surveillance Genes
AEC-conditioned DC showed selective upregulation of chemokines that recruit Th1 cells, but minimal change in chemokines linked to Th2 cell recruitment.
Published research Human Immunology Systems ImmunologyJuly 2011Pneumococcal conjugate vaccination at birth in a high-risk setting: No evidence for neonatal T-cell tolerance
Concerns about the risk of inducing immune deviation-associated "neonatal tolerance" as described in mice have restricted the widespread adoption...
Published research Immunisation Human Immunology Systems Immunology Ear Health Vaccine Trials GroupMarch 2010Toward improved prediction of risk for atopy and asthma among preschoolers: A prospective cohort study
Atopy and asthma are commonly initiated during early life, and there is increasing interest in the development of preventive treatments for at-risk children.
Asthma Published research Human Immunology Systems Immunology -
Education and Qualifications