Rothwell Family Fellow; Head, Airway Epithelial Research
BSc (Hons) PhD
Associate Professor Kicic completed his undergraduate and doctorate degrees at the University of Western Australia, specializing in Molecular Biology and Cell Biology. His research interests lie in tissue engineering and reparative cell biology, particularly focusing on the ability of the cells in the body to repair, including stem cells. Qualified in these areas, he has previously been responsible founding a Stem Cell Unit (Lions Eye Institute, Perth), establishing dedicated laboratories for stem cell research and establishing stem cell isolation and differentiation techniques for both embryonic and adult-derived stem cells. Currently at the Institute, his research has been to investigate the tissue resident stem cells found in the lung and to examine their role in airway repair, identifying target areas for therapeutic application.
His research also focuses on the role of the airway epithelium in the pathogenesis of a number of respiratory diseases including childhood asthma, cystic fibrosis and lung transplant rejection.
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Projects
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Publications
January 2021
Overcoming Challenges to Make Bacteriophage Therapy Standard Clinical Treatment Practice for Cystic Fibrosis
Individuals with cystic fibrosis (CF) are given antimicrobials as prophylaxis against bacterial lung infection, which contributes to the growing emergence of multidrug resistant (MDR) pathogens isolated. Pathogens such as Pseudomonas aeruginosa that are commonly isolated from individuals with CF are armed with an arsenal of protective and virulence mechanisms, complicating eradication and treatment strategies.
Cystic Fibrosis Published research Airway Epithelial Research Subsite: WalyanJanuary 2021ACE2 expression is elevated in airway epithelial cells from older and male healthy individuals but reduced in asthma
COVID-19 is complicated by acute lung injury, and death in some individuals. It is caused by SARS-CoV-2 that requires the ACE2 receptor and serine proteases to enter AEC. We determined what factors are associated with ACE2 expression particularly in patients with asthma and COPD. We obtained lower AEC from 145 people from two independent cohorts, aged 2-89 years, Newcastle (n = 115) and Perth (n = 30), Australia. The Newcastle cohort was enriched with people with asthma (n = 37) and COPD (n = 38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry was assessed by qPCR, and protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AEC.
Asthma Published research Airway Epithelial ResearchJanuary 2021Changes in airway inflammation with pseudomonas eradication in early cystic fibrosis
Neutrophil elastase is a significant risk factor for structural lung disease in cystic fibrosis, and Pseudomonas aeruginosa airway infection is linked with neutrophilic inflammation and substantial respiratory morbidity. We aimed to evaluate how neutrophil elastase (NE) activity changes after P. aeruginosa eradication and influences early disease outcomes. We assessed participants in the AREST CF cohort between 2000 and 2018 who had P. aeruginosa cultured from their routine annual bronchoalveolar lavage (BAL) fluid and who underwent eradication treatment and a post eradication BAL. Factors associated with persistent P. aeruginosa infection, persistent neutrophilic inflammation following eradication and worse structural lung disease one year post-eradication were evaluated.
Cystic Fibrosis Published research Early Childhood Development Airway Epithelial Research Subsite: WalyanFebruary 2021Pseudomonas aeruginosa Resistance to Bacteriophages and Its Prevention by Strategic Therapeutic Cocktail Formulation
Antimicrobial resistance poses a significant threat to modern healthcare as it limits treatment options for bacterial infections, particularly impacting those with chronic conditions such as cystic fibrosis (CF). Viscous mucus accumulation in the lungs of individuals genetically predisposed to CF leads to recurrent bacterial infections, necessitating prolonged antimicrobial chemotherapy. Pseudomonas aeruginosa infections are the predominant driver of CF lung disease, and airway isolates are frequently resistant to multiple antimicrobials.
Cystic Fibrosis Published research Subsite: WalyanJuly 2021Fuel feedstock determines biodiesel exhaust toxicity in a human airway epithelial cell exposure model
Biodiesel is promoted as a sustainable replacement for commercial diesel. Biodiesel fuel and exhaust properties change depending on the base feedstock oil/fat used during creation. The aims of this study were, for the first time, to compare the exhaust exposure health impacts of a wide range of biodiesels made from different feedstocks and relate these effects with the corresponding exhaust characteristics.
Published research Airway Epithelial Research Respiratory Environmental HealthAugust 2021Previous Influenza Infection Exacerbates Allergen Specific Response and Impairs Airway Barrier Integrity in Pre-Sensitized Mice
In this study we assessed the effects of antigen exposure in mice pre‐sensitized with allergen following viral infection on changes in lung function, cellular responses and tight junction expression.
Published research Influenza Airway Epithelial Research Respiratory Environmental Health Subsite: WalyanAugust 2021Cystic fibrosis clinical isolates of aspergillus fumigatus induce similar muco-inflammatory responses in primary airway epithelial cells
Aspergillus is increasingly associated with lung inflammation and mucus plugging in early cystic fibrosis disease during which conidia burden is low and strains appear to be highly diverse. It is unknown whether clinical Aspergillus strains vary in their capacity to induce epithelial inflammation and mucus production.
Cystic Fibrosis Published research Subsite: WalyanSeptember 2021Phage therapy for multi-drug resistant respiratory tract infections
The emergence of multi-drug resistant (MDR) bacteria is recognised today as one of the greatest challenges to public health. As traditional antimicrobials are becoming ineffective and research into new antibiotics is diminishing, a number of alternative treatments for MDR bacteria have been receiving greater attention. Bacteriophage therapies are being revisited and present a promising opportunity to reduce the burden of bacterial infection in this post-antibiotic era.
Published research Subsite: Walyan Immune systemNovember 2021Viral Induced Effects on a Vulnerable Epithelium; Lessons Learned From Paediatric Asthma and Eosinophilic Oesophagitis
The epithelium is integral to the protection of many different biological systems and for the maintenance of biochemical homeostasis. Emerging evidence suggests that particular children have epithelial vulnerabilities leading to dysregulated barrier function and integrity, that resultantly contributes to disease pathogenesis.
Asthma Published research Airway Epithelial Research Children’s Respiratory ScienceNovember 2021Development and validation of a miniaturized bacteriophage host range screening assay against antibiotic resistant Pseudomonas aeruginosa
Antimicrobial resistance is a current global health crisis, and the increasing emergence of multidrug resistant infections has led to the resurgent interest in bacteriophages as an alternative treatment.
Published research Airway Epithelial Research Subsite: WalyanDecember 2021Dysregulated Notch Signaling in the Airway Epithelium of Children with Wheeze
The airway epithelium of children with wheeze is characterized by defective repair that contributes to disease pathobiology. Dysregulation of developmental processes controlled by Notch has been identified in chronic asthma. However, its role in airway epithelial cells of young children with wheeze, particularly during repair, is yet to be determined.
Asthma Published research Airway Epithelial Research P4 Respiratory Health for Kids Bacterial Respiratory Infectious Disease Group Subsite: WalyanAugust 2020Intrauterine growth restriction predisposes to airway inflammation without disruption of epithelial integrity in postnatal male mice
Evidence from animal models demonstrate that intrauterine growth restriction (IUGR) alters airway structure and function which may affect susceptibility to disease. Airway inflammation and dysregulated epithelial barrier properties are features of asthma which have not been examined in the context of IUGR.
Published researchJune 2020Azithromycin Partially Mitigates Dysregulated Repair of Lung Allograft Small Airway Epithelium
Chronic airway injury and dysregulated repair programs are evident in airway epithelium obtained from patients with bronchiolitis obliterans syndrome
Published research Airway Epithelial Research P4 Respiratory Health for KidsJune 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 KidsJune 2020Epithelial Mesenchymal Transition in Respiratory Disease: Fact or Fiction
In this translational review, the mechanisms, roles, and impact of epithelial-mesenchymal transition in chronic lung diseases are discussed
Published research Airway Epithelial Research P4 Respiratory Health for KidsJune 2020COPD-related modification to the airway epithelium permits intracellular residence of nontypeable haemophilus influenzae
Our findings indicate that COPD, cigarette smoke and macrolide antibiotics potentiate the susceptibility to persistent intracellular NTHi
Published research Airway Epithelial ResearchApril 2020Progress in Model Systems of Cystic Fibrosis Mucosal Inflammation to Understand Aberrant Neutrophil Activity
Here we examine the latest findings of neutrophils in pediatric CF lung disease and proposed mechanisms of their pathogenicity
Cystic Fibrosis Published research Airway Epithelial ResearchApril 2020Rhinovirus Infection Is Associated With Airway Epithelial Cell Necrosis and Inflammation via Interleukin-1 in Young Children With Cystic Fibrosis
This study found rhinovirus infection drives necrotic cell death in cystic fibrosis airway epithelial cells
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsApril 2020Blocking Notch3 Signaling Abolishes MUC5AC Production in Airway Epithelial Cells from Asthmatics
We demonstrate that NOTCH3 is a regulator of MUC5AC production
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsJanuary 2019Ground zero—the airway epitheliumNew Page
This chapter will discuss the structure of the airway highlighting the now broad number of cell types that comprise it
Published research Airway Epithelial ResearchApril 2019Elastase Exocytosis by Airway Neutrophils Associates with Early Lung Damage in Cystic Fibrosis Children
Protease elastase exocytosis by airway neutrophils occurs in all cystic fibrosis children, and its cellular measure correlates with early lung damage
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsJuly 2019The Contribution of Geogenic Particulate Matter to Lung Disease in Indigenous Children
The aim of this study was to assess the relationship between dust levels and health in Indigenous children in Western Australia
Published research Aboriginal Health & Wellbeing Human Capability Airway Epithelial Research Bacterial Respiratory Infectious Disease GroupAugust 2019Preterm birth: Born too soon for the developing airway epithelium
This review examines the consequences of preterm birth on the airway epithelium and explores the clinical relevance of currently available models
Published research Airway Epithelial Research Children's Lung HealthOctober 2019Soy Biodiesel Exhaust is More Toxic than Mineral Diesel Exhaust in Primary Human Airway Epithelial Cells
Exposure to biodiesel exhaust resulted in significantly greater cell death and a greater release of immune mediators compared to both air controls and ULSD exhaust
Published research Airway Epithelial Research Respiratory Environmental HealthDecember 2019Azithromycin reduces airway inflammation induced by human rhinovirus in lung allograft recipients
Our data illustrate that rhinovirus infection is capable of infecting upper and lower airway epithelial cells, driving cell death and inflammation
Published research Airway Epithelial Research P4 Respiratory Health for KidsDecember 2018Human Primary Epithelial Cell Models: Promising Tools in the Era of Cystic Fibrosis Personalized Medicine
In this Review, we consolidate the latest updates in the development of primary epithelial cellular model systems relevant for cystic fibrosis
Cystic Fibrosis Published research Airway Epithelial ResearchNovember 2018Elucidating the interaction of CF airway epithelial cells and rhinovirus: Using the host-pathogen relationship to identify future therapeutic strategies
A better understanding of the innate immune responses by CF airway epithelial cells is needed to identify why viral infections are more severe in CF
Cystic Fibrosis Published research Computational Biology Airway Epithelial Research P4 Respiratory Health for KidsNovember 2018Use of a primary epithelial cell screening tool to investigate phage therapy in cystic fibrosis
This study demonstrates the feasibility of utilizing pre-clinical in vitro culture models to screen therapeutic candidates
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsNovember 2018Interleukin-1 is associated with inflammation and structural lung disease in young children with cystic fibrosis
Our data associates IL-1α with early structural lung damage in CF and suggests this pathway as a novel anti-inflammatory target
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsMay 2018Effects of human rhinovirus on epithelial barrier integrity and function in children with asthma
This study demonstrates novel intrinsic differences in tight junctions gene and protein expression between airway epithelial cells of children with and without asthma
Asthma Published research Airway Epithelial Research P4 Respiratory Health for Kids Respiratory Environmental HealthMay 2018Persistent induction of goblet cell differentiation in the airways: Therapeutic approaches
Here we review the current knowledge of key molecular pathways that are dysregulated during persistent goblet cell differentiation
Published research Airway Epithelial Research P4 Respiratory Health for KidsFebruary 2018Visualisation of Multiple Tight Junctional Complexes in Human Airway Epithelial Cells
Apically located tight junctions in airway epithelium perform a fundamental role in controlling macromolecule migration through paracellular spaces.
Published research Airway Epithelial Research P4 Respiratory Health for Kids Respiratory Environmental HealthJanuary 2018Accumulation mode particles and LPS exposure induce TLR-4 dependent and independent inflammatory responses in the lung
We aimed to delineate the effects of LPS and AMP on airway inflammation, and potential contribution to airway disease by measuring airway inflammatory responses
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsJanuary 2018Assessment of p.Phe508del-CFTR functional restoration in pediatric primary cystic fibrosis airway epithelial cells
This study assessed an alternative approach, using a small scale halide assay that can be adapted for a personalized high throughput setting to analyze CFTR function of pAEC.
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsJanuary 2017Hypoxia and sterile inflammation in cystic fibrosis airways: Mechanisms and potential therapies
In this review, we consider recent evidence regarding hypoxia and sterile inflammation in cystic fibrosis airways
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsApril 2017Pulmonary microRNA profiles identify involvement of Creb1 and Sec14l3 in bronchial epithelial changes in allergic asthma
In this study, we aimed to use microRNAs-which are critical regulators of signaling cascades-to identify so far uncharacterized asthma pathogenesis pathways
Asthma Published research Airway Epithelial Research Respiratory Environmental HealthAugust 2017Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity
In disease settings, vitamin D may be important for maintaining optimal lung epithelial integrity and suppressing inflammation, but less is known of its effects prior to disease onset.
Published research Inflammation Cardiometabolic Sunhealth Airway Epithelial Research P4 Respiratory Health for Kids Respiratory Environmental HealthSeptember 2017The AREST CF experience in biobanking - More than just tissues, tubes and time.
Research to further improve outcomes for people with CF is dependent upon well characterised, archived and accessible clinical specimens.
Cystic Fibrosis Published research P4 Respiratory Health for KidsNovember 2017The potential of phage therapy in cystic fibrosis
This review summarises the phage-microbe-human lung interactions in CF that must be addressed to successfully develop and deliver phage to CF airways
Cystic Fibrosis Published research Airway Epithelial ResearchNovember 2017Airway surface liquid pH is not acidic in children with cystic fibrosis
Modulation of ASL pH has been proposed as a therapy for CF. However, evidence that ASL pH is reduced in CF is limited and conflicting.
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsDecember 2017Conditionally reprogrammed primary airway epithelial cells maintain morphology, lineage and disease specific functional characteristics
Here, we show that conditionally reprogrammed airway epithelial cells (CRAECs) can be established from both healthy and diseased phenotypes.
Published research Airway Epithelial Research P4 Respiratory Health for KidsNovember 2016Impaired airway epithelial cell responses from children with asthma to rhinoviral infection
Human rhinovirus infection delays repair and inhibits apoptotic processes in epithelial cells from non-asthmatic and asthmatic children
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsOctober 2016Reduced transforming growth factor β1 (TGF-β1) in the repair of airway epithelial cells of children with asthma
Reduced TGF-β1 levels in paediatric asthmatic airway epithelial cells directly contribute to the dysregulated repair in these cells
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsOctober 2016Of pigs, mice, and men: Understanding early triggers of cystic fibrosis lung disease
Understanding early triggers of Cystic Fibrosis Lung Disease
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsOctober 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 ResearchSeptember 2016The genetic and epigenetic landscapes of the epithelium in asthma
Genetic factors in airway epithelial cells that are functionally associated with asthma pathogenesis
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsJanuary 2016Biodiesel exhaust-induced cytotoxicity and proinflammatory mediator production in human airway epithelial cells
Canola biodiesel exhaust exposure elicits inflammation and reduces viability of human epithelial cell cultures in vitro when compared with ULSD exhaust exposure
Published research Airway Epithelial Research Respiratory Environmental HealthJanuary 2016Alpha-1 antitrypsin mitigates the inhibition of airway epithelial cell repair by neutrophil elastase
Free NE activity is deleterious for epithelial homeostasis and support the hypothesis that proteases in the airway contribute to CF structural lung disease
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsJanuary 2016Airway epithelial repair in health and disease: Orchestrator or simply a player?
This review attempts to highlight migration-specific and cell-extracellular matrix (ECM) aspects of repair used by epithelial cells
Asthma Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsJanuary 2016Early life rhinovirus infection exacerbates house-dust-mite induced lung disease more severely in female mice
Early life rhinovirus infection influences the development of house-dust-mite induced lung disease in female, but not male mice
Published research Airway Epithelial Research Respiratory Environmental HealthJanuary 2016Pressurised metered dose inhaler-spacer technique in young children improves with video instruction
Repeated video instruction over time improves inhaler technique in young children
Asthma Published research Airway Epithelial ResearchAugust 2015Disruption of β-catenin/CBP signaling inhibits human airway epithelial-mesenchymal transition and repair.
The airway epithelium of both children and adults with asthma is relatively undifferentiated characterized by a significantly increased proportion of...
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsJuly 2015Biodiesel exhaust: The need for a systematic approach to health effects research
Biodiesel is a generic term for fuel that can be made from virtually any plant or animal oil via transesterification of triglycerides with an alcohol...
Published research Airway Epithelial Research Respiratory Environmental HealthApril 2015Matrix metalloproteinase activation by free neutrophil elastase contributes to bronchiectasis progression in early cystic fibrosis
The aim of this study was to assess if MMP activation positively correlates with neutrophil elastase activity, disease severity and bronchiectasis in young...
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsApril 2015Productive infection of human embryonic stem cell-derived nkx2.1+ respiratory progenitors with human rhinovirus.
Our experiments provide proof of principle for the use of PSC-derived respiratory epithelial cells in the study of cell-virus interactions.
Published research Infectious Diseases Airway Epithelial Research P4 Respiratory Health for KidsNovember 2014House dust mite induced lung inflammation does not alter circulating vitamin D levels
We hypothesized that allergic inflammation decreases the level of circulating 25(OH)D and tested this using a mice model of house dust mite (HDM) induced...
Published research Vitamin D and Sunlight Airway Epithelial Research P4 Respiratory Health for Kids Respiratory Environmental HealthNovember 2014Determinants of culture success in an airway epithelium sampling program of young children with cystic fibrosis
Determinants of culture success through retrospective analysis of a program of routinely brushing children with Cystic Fibrosis airway disease
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsJuly 2014Biodiesel exhaust-induced cytotoxicity and proinflammatory mediator production in human airway epithelial cells
Our results show that canola biodiesel exhaust exposure elicits inflammation and reduces viability of human epithelial cell cultures in vitro when compared...
Published research Airway Epithelial Research Respiratory Environmental HealthMay 2014Route of exposure alters inflammation and lung function responses to diesel exhaust
In this study, we compared the physiological consequences of short-term exposure to diesel exhaust via inhalation to those due to exposure to the same diesel...
Published research Airway Epithelial Research Respiratory Environmental HealthMarch 2014Rhinovirus exacerbates house-dust-mite induced lung disease in adult mice
In this study, we combined human-rhinovirus infection with a clinically relevant mouse model of aero-allergen exposure using house-dust-mite in an attempt to...
Asthma Published research Airway Epithelial Research Respiratory Environmental HealthDecember 2013Transcription factor p63 regulates key genes and wound repair in human airway epithelial Basal cells
The airway epithelium in asthma displays altered repair and incomplete barrier formation.
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsDecember 2012Regional Differences in Susceptibiity of Bronchial Epithelium to Mesenchymal Transition and Inhibition by the Macrolide Antibiotic Azithromycin
Dysregulated repair following epithelial injury is a key forerunner of disease in many organs, and the acquisition of a mesenchymal phenotype by the injured...
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsSeptember 2012DNA Methylation Profiles of Airway Epithelial Cells and PBMCs from Healthy, Atopic and Asthmatic Children
Allergic inflammation is commonly observed in a number of conditions that are associated with atopy including asthma, eczema and rhinitis.
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsJune 2012Suppression of adrenomedullin contributes to vascular leakage and altered epithelial repair during asthma
The anti-inflammatory peptide, adrenomedullin (AM), and its cognate receptor are expressed in lung tissue, but its pathophysiological significance in airway...
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsJune 2011The airway epithelium is a direct source of matrix degrading enzymes in bronchiolitis obliterans syndrome
Long-term survival after lung transplantation is hindered by the development of bronchiolitis obliterans syndrome (BOS).
Published research Airway Epithelial Research P4 Respiratory Health for KidsMay 2011Bronchial brushings for investigating airway inflammation and remodelling
Asthma is the commonest medical cause for hospital admission for children in Australia, affects more than 300 million people worldwide, and is incurable...
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsFebruary 2011Innate inflammatory responses of pediatric cystic fibrosis airway epithelial cells: Effects of nonviral and viral stimulation
There is controversy regarding whether cystic fibrosis (CF) airway epithelial cells (AECs) are intrinsically proinflammatory.
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsMay 2010Decreased fibronectin production significantly contributes to dysregulated repair of asthmatic epithelium
In human asthma, and experimental allergic airways disease in mice, antigen-presenting cells and CD4(+) effector cells at the airway mucosa orchestrate, and CD4
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsOctober 2009Successful establishment of primary small airway cell cultures in human lung transplantation
The study of small airway diseases such as post-transplant bronchiolitis obliterans syndrome (BOS) is hampered by the difficulty in assessing peripheral airway
Published research Bronchiolitis Airway Epithelial Research P4 Respiratory Health for Kids -
Education and Qualifications
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