Dr Hock Tay
School of Biomedical Sciences and Pharmacy
Immunity and Respiratory Health
Dr Hock Tay’s research examines how and why airway infections can be so problematic for patients with chronic respiratory diseases.
“I was always interested in infection and immunity – in particular how infection moderates the immune system. It's interesting because sometimes when you have infection in patients with chronic lung disease, they have exacerbation of their condition."
“I’m focusing on how pathogens can manipulate the immune response to cause this exacerbation of disease.”
An emerging field of research
According to the central dogma of biology, in order for genes to work (and therefore for cells to be functional) the gene DNA has to be transcribed into RNA, which is translated into protein.
For a long time, it was thought that these proteins did all the important work within the cell. But throughout the past few decades, this central dogma has been turned upside-down.
Researchers have seen that RNA can have a functional role completely aside from their protein-coding function. There is also non-coding RNA that can function within the cell to alter cell activity.
A whole new area of research onto these ‘non-coding RNAs’ has blossomed. One particular type of non-coding RNA are known as microRNAs, of which there are thousands. Each microRNA has a different role – many of which are yet to be described. Importantly, one microRNA has the potential to modulate the level many coding-RNA and thus regulate the level of a range of proteins and integrated signalling networks.
“When I started looking at microRNAs around 10 years ago, their role in complex biological processes was just emerging – some non-coding was even thought to be ‘junk’. It’s only recently with new technologies that allow us to identify all the different microRNAs, that we can see how they are dysregulated in lots of diseases, as well as used in infection.”
“What's so interesting about them is that they can regulate multiple pathways. So that could be really important in disease pathogenesis.”
Hock first heard about these somewhat strange molecules during one of Laureate Professor Paul Foster’s lectures during his Biomedical Science degree at UON.
“Nothing much was known about them, so I was really curious!”
Hock approached Paul about working in his lab throughout his Summer Scholarship, and was excited to get started in the field of RNA and immunology.
“I’d actually applied to work with Paul on microRNAs for my undergraduate research project – but he had already taken on his students for the year so I had to go to a different lab."
“That was a great experience, but I knew that immunology was what I really wanted to work on.”
Regulating the immune cell response
During infection, the early immune response clears the pathogens, while adaptive immune response is called upon if the infection persists or reoccurs.
Throughout his PhD, Hock was focussing on the early responses to infection, as these drive inflammations that cause exacerbation of lung disease.
“The focus was on how these immune cells come in during the early stage, and how that changes the molecular miRNA signatures inside the cells.”
Hock focussed on a few select microRNAs and their role in the immune response, including miRNA-328.
“We found that is acts like a brake for the immune cells. Before infection, miRNA-328 stops the immune cells from becoming active so they’re not just going around destroying everything. Then during an infection, the levels of miRNA-328 drop, and we see upregulation of the immune response. The drop in miRNA-328 enhances the uptake of bacteria into the immune cell to be destroyed.”
In 2016, Hock commenced his prestigious NHMRC Early Career fellowship, which he was awarded to continue his study into the role of non-coding RNAs in respiratory disease.
“I wasn't expecting it. It was a relief really - I can now plan for longer term projects instead of smaller projects which only run for one or two years.”
Throughout his fellowship, Hock will be moving on to study an entirely new group of non-coding RNA: long-non-coding RNAs.
“Where microRNAs are about 23 nucleotides (genetic units) long, long-non-coding RNAs are longer than 200. The mechanisms are completely different and they are actually even harder to study. But a lot of the skills I developed throughout my PhD will still be very useful. I’m really using my PhD as a building block for this project.”
With this fellowship, the University granted Hock two PhD scholarships, and he is taking on his own students for the very first time.
“Everyone tells me having students is going to be challenging but I'm excited about it. I'm excited about the opportunity of teaching someone and at the same time I’m pretty sure I can learn from them too.”
Dr Hock Tay obtained his PhD in Immunology & Microbiology in 2014. In 2015, he received NHMRC Peter Doherty Early Career Fellowship to undertake his post-doctoral research training in Hunter Medical Research Institute at The University of Newcastle, Australia under supervision of Laureate Professor Paul Foster. His researches focus on translational studies using murine model and clinical samples to study the role of the innate immune response and non-coding RNA in regulation of inflammatory responses in lung diseases. Dr Hock Tay has expertise and knowledge in the field of infectious and chronic inflammatory diseases of the lung, immunology, cytokine biology and non-coding RNA. He has 8 years experience in experimental work such as cell culture (primary cells and cell lines), isolation of primary cells, techniques with murine models of respiratory diseases including pharmacological and physiological studies. He has extensive experience in molecular techniques, RNA isolation and protein quantification. He has also established techniques to identify mRNA that are targets for miRNAs in macrophages, by using a biotin-streptavidin pull down approach, followed by RNAseq and bioinformatics techniques.
- PhD (Immunology & Microbiology), University of Newcastle
- Bachelor of Biomedical Sciences, University of Newcastle
- Bachelor of Biomedical Sciences (Hons), University of Newcastle
- Infectious diseases
- Non-coding RNAs
- English (Fluent)
- Mandarin (Fluent)
- Malay (Fluent)
- Cantonese (Fluent)
Fields of Research
|Title||Organisation / Department|
|Research Fellow||University of Newcastle
School of Biomedical Sciences and Pharmacy
For publications that are currently unpublished or in-press, details are shown in italics.
Journal article (27 outputs)
Yuan F, Jiang L, Li Q, Sokulsky L, Wanyan Y, Wang L, et al., 'A Selective a7 Nicotinic Acetylcholine Receptor Agonist, PNU-282987, Attenuates ILC2s Activation and Alternaria-Induced Airway Inflammation', Frontiers in Immunology, 11 (2021) [C1]
Background: The anti-inflammatory effect of an a7nAChR agonist, PNU-282987, has previously been explored in the context of inflammatory disease. However, the effects of PNU-282987... [more]
Background: The anti-inflammatory effect of an a7nAChR agonist, PNU-282987, has previously been explored in the context of inflammatory disease. However, the effects of PNU-282987 on type 2 innate lymphoid cells (ILC2s)-mediated allergic airway inflammation has not yet been established. Aims: To determine the effects of PNU-282987 on the function of ILC2s in the context of IL-33¿ or Alternaria Alternata (AA)¿ induced airway inflammation. Methods: PNU-282987 was administered to mice that received recombinant IL-33 or AA intranasal challenges. Lung histological analysis and flow cytometry were performed to determine airway inflammation and the infiltration and activation of ILC2s. The previously published a7nAChR agonist GTS-21 was employed as a comparable reagent. ILC2s were isolated from murine lung tissue and cultured in vitro in the presence of IL-33, IL-2, and IL-7 with/without either PNU-282987 or GTS-21. The expression of the transcription factors GATA3, IKK, and NF-¿B were also determined. Results: PNU-282987 and GTS-21 significantly reduced goblet cell hyperplasia in the airway, eosinophil infiltration, and ILC2s numbers in BALF, following IL-33 or AA challenge. In vitro IL-33 stimulation of isolated lung ILC2s showed a reduction of GATA3 and Ki67 in response to PNU-282987 or GTS-21 treatments. There was a significant reduction in IKK and NF-¿B phosphorylation in the PNU-282987¿treated group when compared to the GTS-21¿treated ILC2s. Conclusion: PNU-282987 inhibits ILC2-associated airway inflammation, where its effects were comparable to that of GTS-21.
Foster PS, Tay HL, Hogan SP, 'Uridine diphosphate-glucose/P2Y
Allergic asthma is a chronic inflammatory airway disease characterized by dysregulated type 2 immune responses, including degranulating airway eosinophils that induce tissue damag... [more]
Allergic asthma is a chronic inflammatory airway disease characterized by dysregulated type 2 immune responses, including degranulating airway eosinophils that induce tissue damage and airway hyperresponsiveness (AHR). The type 2 cytokines interleukin 5 (IL-5) and IL-13 and the eosinophil-specific chemokine CCL11/CCL24/CCL26 axis recruit, activate, and regulate eosinophils in the airways. In this issue of the JCI, Karcz et al. identified a mechanism involving the nucleotide sugar UDP-glucose (UDP-G) and the purinergic receptor P2Y14R in amplifying eosinophil accumulation in the lung. During type 2 inflammation, UDP-G activates P2Y14R on eosinophils, inducing the cells to move and migrate into the lung. Pharmacologically or genetically inhibiting P2Y14R on eosinophils attenuated eosinophil infiltration and AHR. Future experiments, including identifying additional type 2 factors regulating P2Y14R expression on lung eosinophils, are necessary to ascertain the impact of targeting P2Y14R as an alternative or adjunctive therapy to current type 2 biologics for the treatment of asthma.
Barnes JL, Plank MW, Asquith K, Maltby S, Sabino LR, Kaiko GE, et al., 'T-helper 22 cells develop as a distinct lineage from Th17 cells during bacterial infection and phenotypic stability is regulated by T-bet.', Mucosal immunology, (2021)
Pan L-L, Ren Z, Tu X, Liu H, Tay HL, Li J, et al., 'GPR109A deficiency promotes IL-33 overproduction and type 2 immune response in food allergy in mice.', Allergy, 76 2613-2616 (2021)
Liu G, Baird AW, Parsons MJ, Fan K, Skerrett-Byrne DA, Nair PM, et al., 'Platelet activating factor receptor acts to limit colitis-induced liver inflammation', FASEB JOURNAL, 34 7718-7732 (2020) [C1]
Tay HL, Foster PS, 'Biologics or immunotherapeutics for asthma?', PHARMACOLOGICAL RESEARCH, 158 (2020) [C1]
Ali MK, Kim RY, Brown AC, Mayall JR, Karim R, Pinkerton JW, et al., 'Crucial role for lung iron level and regulation in the pathogenesis and severity of asthma', EUROPEAN RESPIRATORY JOURNAL, 55 (2020) [C1]
Hadjigol S, Netto KG, Maltby S, Tay HL, Nguyen TH, Hansbro NG, et al., 'Lipopolysaccharide induces steroid-resistant exacerbations in a mouse model of allergic airway disease collectively through IL-13 and pulmonary macrophage activation', Clinical and Experimental Allergy, 50 82-94 (2020) [C1]
Background: Acute exacerbations of asthma represent a major burden of disease and are often caused by respiratory infections. Viral infections are recognized as significant trigge... [more]
Background: Acute exacerbations of asthma represent a major burden of disease and are often caused by respiratory infections. Viral infections are recognized as significant triggers of exacerbations; however, less is understood about the how microbial bioproducts such as the endotoxin (lipopolysaccharide (LPS)) trigger episodes. Indeed, increased levels of LPS have been linked to asthma onset, severity and steroid resistance. Objective: The goal of this study was to identify mechanisms underlying bacterial-induced exacerbations by employing LPS as a surrogate for infection. Methods: We developed a mouse model of LPS-induced exacerbation on the background of pre-existing type-2 allergic airway disease (AAD). Results: LPS-induced exacerbation was characterized by steroid-resistant airway hyperresponsiveness (AHR) and an exaggerated inflammatory response distinguished by increased numbers of infiltrating neutrophils/macrophages and elevated production of lung inflammatory cytokines, including TNFa, IFN¿, IL-27 and MCP-1. Expression of the type-2 associated inflammatory factors such as IL-5 and IL-13 were elevated in AAD but not altered by LPS exposure. Furthermore, AHR and airway inflammation were no longer suppressed by corticosteroid (dexamethasone) treatment after LPS exposure. Depletion of pulmonary macrophages by administration of 2-chloroadenosine into the lungs suppressed AHR and reduced IL-13, TNFa and IFN¿ expression. Blocking IL-13 function, through either IL-13-deficiency or administration of specific blocking antibodies, also suppressed AHR and airway inflammation. Conclusions & Clinical Relevance: We present evidence that IL-13 and innate immune pathways (in particular pulmonary macrophages) contribute to LPS-induced exacerbation of pre-existing AAD and provide insight into the complex molecular processes potentially underlying microbial-induced exacerbations.
Hoefel G, Tay H, Foster P, 'MicroRNAs in Lung Diseases', Chest, 156 991-1000 (2019) [C1]
Chronic inflammatory diseases of the lung are often life-threatening and are a leading cause of morbidity in our communities. MicroRNAs (miRs) are now recognized to play critical ... [more]
Chronic inflammatory diseases of the lung are often life-threatening and are a leading cause of morbidity in our communities. MicroRNAs (miRs) are now recognized to play critical roles in a wide range of cellular functions, including the regulation of immunologic processes, which are often dysregulated in chronic respiratory diseases. These small noncoding RNA molecules regulate networks of genes by inhibiting translation through the targeting of one or multiple messenger RNA transcripts. This review highlights discoveries that identify important roles for miRs in the regulation of specific pathogenic features of a range of diseases. Furthermore, experimental evidence suggests that pharmacologic inhibition of miR function or delivery of mimics may have therapeutic potential. The review also therefore discusses the potential utility and limitations of therapeutically targeting these molecules and their downstream pathways.
Liu G, Mateer SW, Hsu A, Goggins BJ, Tay H, Mathe A, et al., 'Platelet activating factor receptor regulates colitis-induced pulmonary inflammation through the NLRP3 inflammasome', Mucosal Immunology, 12 862-873 (2019) [C1]
Extra-intestinal manifestations (EIM) are common in inflammatory bowel disease (IBD). One such EIM is sub-clinical pulmonary inflammation, which occurs in up to 50% of IBD patient... [more]
Extra-intestinal manifestations (EIM) are common in inflammatory bowel disease (IBD). One such EIM is sub-clinical pulmonary inflammation, which occurs in up to 50% of IBD patients. In animal models of colitis, pulmonary inflammation is driven by neutrophilic infiltrations, primarily in response to the systemic bacteraemia and increased bacterial load in the lungs. Platelet activating factor receptor (PAFR) plays a critical role in regulating pulmonary responses to infection in conditions, such as chronic obstructive pulmonary disease and asthma. We investigated the role of PAFR in pulmonary EIMs of IBD, using dextran sulfate sodium (DSS) and anti-CD40 murine models of colitis. Both models induced neutrophilic inflammation, with increased TNF and IL-1ß levels, bacterial load and PAFR protein expression in mouse lungs. Antagonism of PAFR decreased lung neutrophilia, TNF, and IL-1ß in an NLRP3 inflammasome-dependent manner. Lipopolysaccharide from phosphorylcholine (ChoP)-positive bacteria induced NLRP3 and caspase-1 proteins in human alveolar epithelial cells, however antagonism of PAFR prevented NLRP3 activation by ChoP. Amoxicillin reduced bacterial populations in the lungs and reduced NLRP3 inflammasome protein levels, but did not reduce PAFR. These data suggest a role for PAFR in microbial pattern recognition and NLRP3 inflammasome signaling in the lung.
Mateer SW, Mathe A, Bruce J, Liu G, Maltby S, Fricker M, et al., 'IL-6 Drives Neutrophil-Mediated Pulmonary Inflammation Associated with Bacteremia in Murine Models of Colitis', American Journal of Pathology, 188 1625-1639 (2018) [C1]
Inflammatory bowel disease (IBD) is associated with several immune-mediated extraintestinal manifestations. More than half of all IBD patients have some form of respiratory pathol... [more]
Inflammatory bowel disease (IBD) is associated with several immune-mediated extraintestinal manifestations. More than half of all IBD patients have some form of respiratory pathology, most commonly neutrophil-mediated diseases, such as bronchiectasis and chronic bronchitis. Using murine models of colitis, we aimed to identify the immune mechanisms driving pulmonary manifestations of IBD. We found increased neutrophil numbers in lung tissue associated with the pulmonary vasculature in both trinitrobenzenesulfonic acid¿ and dextran sulfate sodium¿induced models of colitis. Analysis of systemic inflammation identified that neutrophilia was associated with bacteremia and pyrexia in animal models of colitis. We further identified IL-6 as a systemic mediator of neutrophil recruitment from the bone marrow of dextran sulfate sodium animals. Functional inhibition of IL-6 led to reduced systemic and pulmonary neutrophilia, but it did not attenuate established colitis pathology. These data suggest that systemic bacteremia and pyrexia drive IL-6 secretion, which is a critical driver for pulmonary manifestation of IBD. Targeting IL-6 may reduce neutrophil-associated extraintestinal manifestations in IBD patients.
Maltby S, Lochrin AJ, Bartlett B, Tay HL, Weaver J, Poulton IJ, et al., 'Osteoblasts Are Rapidly Ablated by Virus-Induced Systemic Inflammation following Lymphocytic Choriomeningitis Virus or Pneumonia Virus of Mice Infection in Mice', Journal of Immunology, 200 632-642 (2018) [C1]
A link between inflammatory disease and bone loss is now recognized. However, limited data exist on the impact of virus infection on bone loss and regeneration. Bone loss results ... [more]
A link between inflammatory disease and bone loss is now recognized. However, limited data exist on the impact of virus infection on bone loss and regeneration. Bone loss results from an imbalance in remodeling, the physiological process whereby the skeleton undergoes continual cycles of formation and resorption. The specific molecular and cellular mechanisms linking virus-induced inflammation to bone loss remain unclear. In the current study, we provide evidence that infection of mice with either lymphocytic choriomeningitis virus (LCMV) or pneumonia virus of mice (PVM) resulted in rapid and substantial loss of osteoblasts from the bone surface. Osteoblast ablation was associated with elevated levels of circulating inflammatory cytokines, including TNF-a, IFN-g, IL-6, and CCL2. Both LCMV and PVM infections resulted in reduced osteoblast-specific gene expression in bone, loss of osteoblasts, and reduced serum markers of bone formation, including osteocalcin and procollagen type 1 N propeptide. Infection of Rag-1-deficient mice (which lack adaptive immune cells) or specific depletion of CD8+ T lymphocytes limited osteoblast loss associated with LCMV infection. By contrast, CD8+ T cell depletion had no apparent impact on osteoblast ablation in association with PVM infection. In summary, our data demonstrate dramatic loss of osteoblasts in response to virus infection and associated systemic inflammation. Further, the inflammatory mechanisms mediating viral infection-induced bone loss depend on the specific inflammatory condition.
Nguyen TH, Maltby S, Tay HL, Eyers F, Foster PS, Yang M, 'Identification of IFN- and IL-27 as Critical Regulators of Respiratory Syncytial Virus-Induced Exacerbation of Allergic Airways Disease in a Mouse Model', Journal of Immunology, 200 237-247 (2018) [C1]
Respiratory syncytial virus (RSV) infection induces asthma exacerbations, which leads to worsening of clinical symptoms and may result in a sustained decline in lung function. Exa... [more]
Respiratory syncytial virus (RSV) infection induces asthma exacerbations, which leads to worsening of clinical symptoms and may result in a sustained decline in lung function. Exacerbations are the main cause of morbidity and mortality associated with asthma, and significantly contribute to asthma-associated healthcare costs. Although glucocorticoids are used to manage exacerbations, some patients respond to them poorly. The underlying mechanisms associated with steroid-resistant exacerbations remain largely unknown. We have previously established a mouse model of RSV-induced exacerbation of allergic airways disease, which mimics hallmark clinical features of asthma. In this study, we have identified key roles for macrophage IFN-¿ and IL-27 in the regulation of RSV-induced exacerbation of allergic airways disease. Production of IFN-¿ and IL-27 was steroid-resistant, and neutralization of IFN-¿ or IL-27 significantly suppressed RSV-induced steroid-resistant airway hyperresponsiveness and airway inflammation. We have previously implicated activation of pulmonary macrophage by TNF-a and/or MCP-1 in the mechanisms of RSV-induced exacerbation. Stimulation of pulmonary macrophages with TNF-a and/or MCP-1 induced expression of both IFN-¿ and IL-27. Our findings highlight critical roles for IFN-¿ and IL-27, downstream of TNF-a and MCP-1, in the mechanism of RSV-induced exacerbation. Thus, targeting the pathways that these factors activate may be a potential therapeutic approach for virus-induced asthma exacerbations.
Liu G, Cooley MA, Nair PM, Donovan C, Hsu AC, Jarnicki AG, et al., 'Airway remodelling and inflammation in asthma are dependent on the extracellular matrix protein fibulin-1c', JOURNAL OF PATHOLOGY, 243 510-523 (2017) [C1]
Plank MW, Kaiko GE, Maltby S, Weaver J, Tay HL, Shen W, et al., 'Th22 Cells Form a Distinct Th Lineage from Th17 Cells In Vitro with Unique Transcriptional Properties and Tbet-Dependent Th1 Plasticity.', JOURNAL OF IMMUNOLOGY, 198 2182-2190 (2017) [C1]
Tay H, Wark PAB, Bartlett NW, 'Advances in the treatment of virus-induced asthma', Expert Review of Respiratory Medicine, 10 629-641 (2016) [C1]
ABSTRACT: Viral exacerbations continue to represent the major burden in terms of morbidity, mortality and health care costs associated with asthma. Those at greatest risk for acut... [more]
ABSTRACT: Viral exacerbations continue to represent the major burden in terms of morbidity, mortality and health care costs associated with asthma. Those at greatest risk for acute asthma are those with more severe airways disease and poor asthma control. It is this group with established asthma in whom acute exacerbations triggered by virus infections remain a serious cause of increased morbidity. A range of novel therapies are emerging to treat asthma and in particular target this group with poor disease control, and in most cases their efficacy is now being judged by their ability to reduce the frequency of acute exacerbations. Critical for the development of new treatment approaches is an improved understanding of virus-host interaction in the context of the asthmatic airway. This requires research into the virology of the disease in physiological models in conjunction with detailed phenotypic characterisation of asthma patients to identify targets amenable to therapeutic intervention.
Xiang Y, Eyers F, Herbert C, Tay HL, Foster PS, Yang M, 'MicroRNA-487b is a negative regulator of macrophage activation by targeting IL-33 production', Journal of Immunology, 196 3421-3428 (2016) [C1]
MicroRNAs (miRNAs) are short noncoding RNAs that regulate a broad spectrum of biological processes, including immune responses. Although the contributions of miRNAs to the functio... [more]
MicroRNAs (miRNAs) are short noncoding RNAs that regulate a broad spectrum of biological processes, including immune responses. Although the contributions of miRNAs to the function of immune cells are beginning to emerge, their specific roles remain largely unknown. IL-33 plays an important role in macrophage activation for innate host defense and proinflammatory responses. In this study, we report that miR-487b can suppress the levels of mRNA and protein for IL-33 during the differentiation of bone marrow-derived macrophages (BMDMs). This results in inhibition of IL-33-induced expression of Ag-presenting and costimulatory molecules and proinflammatory mediators. A luciferase assay showed that miR-487b binds to the IL-33 39-untranslated region. We also confirmed that IL-33 directly promotes the activation of BMDMs by increasing the expression of MHC class I, MHC class II, CD80/CD86, and inducible NO synthase (iNOS) in a dose-dependent manner. Exposure of BMDMs to the TLR4 ligand, LPS, decreased miR-487b expression, increased IL-33 transcript levels, and induced the production of proinflammatory mediators (e.g., iNOS, IL-1b, IL-6, and TNF-a). Treatment with a specific inhibitor of miR-487b function also resulted in increased levels of IL-33 mRNA, which augmented LPS-induced expression of these inflammatory mediators in macrophages. Collectively, our results indicate that miR-487b plays a negative regulatory role in macrophages by controlling the levels of IL-33 transcript and protein to fine-tune innate immune host defense and proinflammatory responses of these cells. Thus, miR-487b plays an important role in the regulation of macrophage homeostasis and activation by targeting IL-33 transcripts.
Zhou H, Zhang J, Eyers F, Xiang Y, Herbert C, Tay HL, et al., 'Identification of the microRNA networks contributing to macrophage differentiation and function', Oncotarget, 7 28806-28820 (2016) [C1]
Limited evidence is available about the specific miRNA networks that regulate differentiation of specific immune cells. In this study, we characterized miRNA expression and associ... [more]
Limited evidence is available about the specific miRNA networks that regulate differentiation of specific immune cells. In this study, we characterized miRNA expression and associated alterations in expression with putative mRNA targets that are critical during differentiation of macrophages. In an effort to map the dynamic changes in the bone marrow (BM), we profiled whole BM cultures during differentiation into macrophages. We identified 112 miRNAs with expression patterns that were differentially regulated 5-fold or more during BMDM development. With TargetScan and MeSH databases, we identified 1267 transcripts involved in 30 canonical pathways linked to macrophage biology as potentially regulated by these specific 112 miRNAs. Furthermore, by employing miRanda and Ingenuity Pathways Analysis (IPA) analysis systems, we identified 18 miRNAs that are temporally linked to the expression of CSF1R, CD36, MSR1 and SCARB1; 7 miRNAs linked to the regulation of the transcription factors RUNX1 and PU.1, and 14 miRNAs target the nuclear receptor PPARa and PPAR¿. This novel information provides an important reference resource for further study of the functional links between miRNAs and their target mRNAs for the regulation of differentiation and function of macrophages.
Tay HL, Kaiko GE, Plank M, Li J, Maltby S, Essilfie A-T, et al., 'Correction: Antagonism of miR-328 Increases the Antimicrobial Function of Macrophages and Neutrophils and Rapid Clearance of Non-typeable Haemophilus Influenzae (NTHi) from Infected Lung.', PLoS pathogens, 11 e1004956 (2015) [O1]
Li JJ, Tay HL, Maltby S, Xiang Y, Eyers F, Hatchwell L, et al., 'MicroRNA-9 regulates steroid-resistant airway hyperresponsiveness by reducing protein phosphatase 2A activity', Journal of Allergy and Clinical Immunology, 136 462-473 (2015) [C1]
Background Steroid-resistant asthma is a major clinical problem that is linked to activation of innate immune cells. Levels of IFN-¿ and LPS are often increased in these patients.... [more]
Background Steroid-resistant asthma is a major clinical problem that is linked to activation of innate immune cells. Levels of IFN-¿ and LPS are often increased in these patients. Cooperative signaling between IFN-¿/LPS induces macrophage-dependent steroid-resistant airway hyperresponsiveness (AHR) in mouse models. MicroRNAs (miRs) are small noncoding RNAs that regulate the function of innate immune cells by controlling mRNA stability and translation. Their role in regulating glucocorticoid responsiveness and AHR remains unexplored. Objective IFN-¿ and LPS synergistically increase the expression of miR-9 in macrophages and lung tissue, suggesting a role in the mechanisms of steroid resistance. Here we demonstrate the role of miR-9 in IFN-¿/LPS-induced inhibition of dexamethasone (DEX) signaling in macrophages and in induction of steroid-resistant AHR. Methods MiRNA-9 expression was assessed by means of quantitative RT-PCR. Putative miR-9 targets were determined in silico and confirmed in luciferase reporter assays. miR-9 function was inhibited with sequence-specific antagomirs. The efficacy of DEX was assessed by quantifying glucocorticoid receptor (GR) cellular localization, protein phosphatase 2A (PP2A) activity, and AHR. Results Exposure of pulmonary macrophages to IFN-¿/LPS synergistically induced miR-9 expression; reduced levels of its target transcript, protein phosphatase 2 regulatory subunit B (B56) d isoform; attenuated PP2A activity; and inhibited DEX-induced GR nuclear translocation. Inhibition of miR-9 increased both PP2A activity and GR nuclear translocation in macrophages and restored steroid sensitivity in multiple models of steroid-resistant AHR. Pharmacologic activation of PP2A restored DEX efficacy and inhibited AHR. MiR-9 expression was increased in sputum of patients with neutrophilic but not those with eosinophilic asthma. Conclusion MiR-9 regulates GR signaling and steroid-resistant AHR. Targeting miR-9 function might be a novel approach for the treatment of steroid-resistant asthma.
Plank MW, Maltby S, Tay HL, Stewart J, Eyers F, Hansbro PM, Foster PS, 'MicroRNA Expression Is Altered in an Ovalbumin-Induced Asthma Model and Targeting miR-155 with Antagomirs Reveals Cellular Specificity.', PloS one, 10 1-25 (2015) [C1]
Tay HL, Kaiko GE, Plank M, Li JJ, Maltby S, Essilfie AT, et al., 'Antagonism of miR-328 Increases the Antimicrobial Function of Macrophages and Neutrophils and Rapid Clearance of Non-typeable Haemophilus Influenzae (NTHi) from Infected Lung', PLoS Pathogens, 11 (2015) [C1]
Pathogenic bacterial infections of the lung are life threatening and underpin chronic lung diseases. Current treatments are often ineffective potentially due to increasing antibio... [more]
Pathogenic bacterial infections of the lung are life threatening and underpin chronic lung diseases. Current treatments are often ineffective potentially due to increasing antibiotic resistance and impairment of innate immunity by disease processes and steroid therapy. Manipulation miRNA directly regulating anti-microbial machinery of the innate immune system may boost host defence responses. Here we demonstrate that miR-328 is a key element of the host response to pulmonary infection with non-typeable haemophilus influenzae and pharmacological inhibition in mouse and human macrophages augments phagocytosis, the production of reactive oxygen species, and microbicidal activity. Moreover, inhibition of miR-328 in respiratory models of infection, steroid-induced immunosuppression, and smoke-induced emphysema enhances bacterial clearance. Thus, miRNA pathways can be targeted in the lung to enhance host defence against a clinically relevant microbial infection and offer a potential new anti-microbial approach for the treatment of respiratory diseases.
Maltby S, Hansbro NG, Tay HL, Stewart J, Plank M, Donges B, et al., 'Production and differentiation of myeloid cells driven by proinflammatory cytokines in response to acute pneumovirus infection in mice.', J Immunol, 193 4072-4082 (2014) [C1]
Tay HL, Plank M, Collison A, Mattes J, Kumar RK, Foster PS, 'MicroRNA: Potential biomarkers and therapeutic targets for allergic asthma?', Annals of Medicine, 46 633-639 (2014) [C1]
MicroRNAs are small non-coding RNAs that bind to multiple target mRNAs to control gene expression post-transcriptionally by inhibiting translation. In mammalian cells, microRNAs p... [more]
MicroRNAs are small non-coding RNAs that bind to multiple target mRNAs to control gene expression post-transcriptionally by inhibiting translation. In mammalian cells, microRNAs play important roles in a diverse array of cellular processes (e.g. cell proliferation and differentiation). However, alterations in their levels may compromise cellular function, predisposing to disease. In this review, we discuss microRNAs that have been linked with pathogenesis of asthma and propose functional roles in the regulation of disease. MicroRNAs have the potential to be biomarkers for asthma and provide the platform for the development of new classes of therapeutic compounds.
Foster PS, Plank MW, Collison AM, Tay HL, Kaiko GE, Li J, et al., 'The emerging role of microRNAs in regulating immune and inflammatory responses in the lung', Immunological Reviews, 253 198-215 (2013) [C1]
Li JJ, Tay HL, Plank M, Essilfie A-T, Hansbro PM, Foster PS, Yang M, 'Activation of Olfactory Receptors on Mouse Pulmonary Macrophages Promotes Monocyte Chemotactic Protein-1 Production', PLOS ONE, 8 (2013) [C1]
|Show 24 more journal articles|
Review (3 outputs)
Foster PS, Maltby S, Rosenberg HF, Tay HL, Hogan SP, Collison AM, et al., 'Modeling T
In this review, we highlight experiments conducted in our laboratories that have elucidated functional roles for CD4+ T-helper type-2 lymphocytes (TH2 cells), their associated cyt... [more]
In this review, we highlight experiments conducted in our laboratories that have elucidated functional roles for CD4+ T-helper type-2 lymphocytes (TH2 cells), their associated cytokines, and eosinophils in the regulation of hallmark features of allergic asthma. Notably, we consider the complexity of type-2 responses and studies that have explored integrated signaling among classical TH2 cytokines (IL-4, IL-5, and IL-13), which together with CCL11 (eotaxin-1) regulate critical aspects of eosinophil recruitment, allergic inflammation, and airway hyper-responsiveness (AHR). Among our most important findings, we have provided evidence that the initiation of TH2 responses is regulated by airway epithelial cell-derived factors, including TRAIL and MID1, which promote TH2 cell development via STAT6-dependent pathways. Further, we highlight studies demonstrating that microRNAs are key regulators of allergic inflammation and potential targets for anti-inflammatory therapy. On the background of TH2 inflammation, we have demonstrated that innate immune cells (notably, airway macrophages) play essential roles in the generation of steroid-resistant inflammation and AHR secondary to allergen- and pathogen-induced exacerbations. Our work clearly indicates that understanding the diversity and spatiotemporal role of the inflammatory response and its interactions with resident airway cells is critical to advancing knowledge on asthma pathogenesis and the development of new therapeutic approaches.
Maltby S, Tay HL, Yang M, Foster PS, 'Mouse models of severe asthma: Understanding the mechanisms of steroid resistance, tissue remodelling and disease exacerbation', Respirology (2017) [C1]
Severe asthma has significant disease burden and results in high healthcare costs. While existing therapies are effective for the majority of asthma patients, treatments for indiv... [more]
Severe asthma has significant disease burden and results in high healthcare costs. While existing therapies are effective for the majority of asthma patients, treatments for individuals with severe asthma are often ineffective. Mouse models are useful to identify mechanisms underlying disease pathogenesis and for the preclinical assessment of new therapies. In fact, existing mouse models have contributed significantly to our understanding of allergic/eosinophilic phenotypes of asthma and facilitated the development of novel targeted therapies (e.g. anti-IL-5 and anti-IgE). These therapies are effective in relevant subsets of severe asthma patients. Unfortunately, non-allergic/non-eosinophilic asthma, steroid resistance and disease exacerbation remain areas of unmet clinical need. No mouse model encompasses all features of severe asthma. However, mouse models can provide insight into pathogenic pathways that are relevant to severe asthma. In this review, as examples, we highlight models relevant to understanding steroid resistance, chronic tissue remodelling and disease exacerbation. Although these models highlight the complexity of the immune pathways that may underlie severe asthma, they also provide insight into new potential therapeutic approaches.
Maltby S, Plank M, Tay HL, Collison A, Foster PS, 'Targeting MicroRNA function in respiratory diseases: Mini-review', Frontiers in Physiology (2016) [C1]
Conference (9 outputs)
Liu G, Mateer S, Hsu A, Goggins B, Tay H, Mathe A, et al., 'Platelet activating factor receptor regulates colitis-induced pulmonary inflammation through the NLRP3 inflammasome', EUROPEAN JOURNAL OF IMMUNOLOGY, Beijing, PEOPLES R CHINA (2019)
Tay HL, Hsu A, Nguyen T, Donovan C, Collison A, Mattes J, et al., 'Interleukin-36 gamma: Roles in lungs innate immunity, inflammation and allergy', CYTOKINE, Int Cytokine & Interferon Soc, Kanazawa, JAPAN (2017)
Tay H, Kaiko G, Plank M, Li J, Essilfie A, Maltby S, et al., 'THE ROLE OF MIR-328 IN RESPIRATORY DISEASES', RESPIROLOGY, Queensland, AUSTRALIA (2015) [E3]
Tay H, Kaiko G, Hansbro P, Foster P, 'The role of miRNA in regulating bacterial clearance', JOURNAL OF IMMUNOLOGY, Honolulu, HI (2013) [E3]
Kaiko GE, Tay HL, Plank MW, Hansbro PM, Foster PS, 'MicroRNA regulate bacterial phagocytosis in the lung', Immunology: Abstracts of the European Congress of Immunology, Glasgow, Scotland (2012) [E3]
Kaiko GE, Phipps S, Plank MW, Tay HL, Lam CE, Foster PS, 'Inhibition of microRNA reverses CD8 T cell exhaustion and improves immunity against respiratory virus infection', Respirology, Canberra, ACT (2012) [E3]
Plank MW, Kaiko GE, Luck H, Li J, Mattes J, Hansbro PM, Foster PS, 'The role of micrornas in CD4 T cell function', Respirology, Canberra, ACT (2012) [E3]
Tay HL, Kaiko GE, Plank MW, Mattes J, Hansbro PM, Foster PS, 'MiRNAs regulate bacterial infection in lungs', Respirology, Canberra, ACT (2012) [E3]
Foster PS, Tay HL, Kaiko GE, Plank MW, Mattes J, Hansbro PM, 'MiRNA and its roles in regulating bacterial infection in lungs', American Journal of Respiratory and Critical Care Medicine, Denver, CO (2011) [E3]
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Grants and Funding
|Number of grants||9|
Click on a grant title below to expand the full details for that specific grant.
20211 grants / $55,000
Development of translational prognostic tool to identify T cell responses in COVID 19 patients$55,000
Funding body: Hunter Medical Research Institute
|Funding body||Hunter Medical Research Institute|
|Project Team||Conjoint Professor Peter Wark, Laureate Professor Paul Foster, Doctor Hock Tay, Doctor Gerard Kaiko, A/Prof Brian Oliver, A/Prof Ben Kwan, Dr Carlos Riveros|
|Type Of Funding||C3300 – Aust Philanthropy|
20191 grants / $1,318,180
Funding body: NHMRC (National Health & Medical Research Council)
|Funding body||NHMRC (National Health & Medical Research Council)|
|Project Team||Laureate Professor Paul Foster, Doctor Hock Tay, Doctor Ming Yang, Doctor Ming Yang|
|Type Of Funding||Aust Competitive - Commonwealth|
20172 grants / $774,921
Characterising the pro-inflammatory role of IL-36¿/IL-36R in pathogen-induced exacerbations of asthma and COPD$764,921
Funding body: NHMRC (National Health & Medical Research Council)
Countess II FL$10,000
Funding body: NSW Ministry of Health
|Funding body||NSW Ministry of Health|
|Project Team||Doctor Malcolm Starkey, Doctor Adam Collison, Doctor Hock Tay, Doctor Aniruddh Deshpande, Doctor Gang Liu, Doctor Jemma Mayall|
|Scheme||Medical Research Support Program (MRSP)|
|Type Of Funding||C2400 – Aust StateTerritoryLocal – Other|
20164 grants / $439,138
Funding body: NHMRC (National Health & Medical Research Council)
|Funding body||NHMRC (National Health & Medical Research Council)|
|Project Team||Doctor Hock Tay|
|Scheme||Early Career Fellowships|
|Type Of Funding||Aust Competitive - Commonwealth|
Funding body: University of Newcastle
|Funding body||University of Newcastle|
|Project Team||Doctor Hock Tay|
|Scheme||NHMRC ECF Support|
|Type Of Funding||Internal|
Funding body: Hunter Medical Research Institute
Funding body: The University of Newcastle - Research and Innovation Division
|Funding body||The University of Newcastle - Research and Innovation Division|
Malcolm Starkey, Chantal Donovan, Richard Kim, Andrew Reid, Hock Tay
|Scheme||Research Advantage Funding|
|Type Of Funding||Not Known|
20141 grants / $20,000
Virus Infections Change the Bone Marrow: Effects on Immunity, Bone Development and Inflammatory Disease$20,000
Funding body: Hunter Medical Research Institute
Number of supervisions
|Commenced||Level of Study||Research Title||Program||Supervisor Type|
|2017||PhD||Understanding the Link Between Fungal Exposure and Severe Asthma||PhD (Immunology & Microbiol), College of Health, Medicine and Wellbeing, The University of Newcastle||Principal Supervisor|
|2017||PhD||Characterising Proinflammatory Role of IL-36y/IL-36R in Pathogen-induced Exacerbations of Asthma||PhD (Immunology & Microbiol), College of Health, Medicine and Wellbeing, The University of Newcastle||Principal Supervisor|
|2017||PhD||Determining the Roles of Non-coding RNAs in Pulmonary Innate Immune Responses||PhD (Immunology & Microbiol), College of Health, Medicine and Wellbeing, The University of Newcastle||Principal Supervisor|
November 13, 2015