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|
|NHMRC 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 (11 outputs)
Tay H, Wark PAB, Bartlett NW, 'Advances in the treatment of virus-induced asthma', Expert Review of Respiratory Medicine, 10 629-641 (2016)
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.', J Immunol, 196 3421-3428 (2016)
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)
Tay HL, Kaiko GE, Plank M, Li J, Maltby S, Essilfie AT, 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]
Â© 2015 American Academy of Allergy, Asthma & Immunology.Background Steroid-resistant asthma is a major clinical problem that is linked to activation of innate immune cells. Level... [more]
Â© 2015 American Academy of Allergy, Asthma & Immunology.Background Steroid-resistant asthma is a major clinical problem that is linked to activation of innate immune cells. Levels of IFN-Â¿ and LPS are often increased in these patients. Cooperative signaling between IFN-Â¿/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-Â¿ 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-Â¿/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-Â¿/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]
Â© 2015 Tay et al.Pathogenic bacterial infections of the lung are life threatening and underpin chronic lung diseases. Current treatments are often ineffective potentially due to ... [more]
Â© 2015 Tay et al.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]
Â© 2014 Informa UK, Ltd.MicroRNAs are small non-coding RNAs that bind to multiple target mRNAs to control gene expression post-transcriptionally by inhibiting translation. In mamm... [more]
Â© 2014 Informa UK, Ltd.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 8 more journal articles|
Review (1 outputs)
Maltby S, Plank M, Tay HL, Collison A, Foster PS, 'Targeting MicroRNA Function in Respiratory Diseases: Mini-Review.', Front Physiol (2016)
Conference (4 outputs)
Tay H, Kaiko G, Hansbro P, Foster P, 'The role of miRNA in regulating bacterial clearance', JOURNAL OF IMMUNOLOGY (2013) [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 (2012) [E3]
Tay HL, Kaiko GE, Plank MW, Mattes J, Hansbro PM, Foster PS, 'MiRNAs regulate bacterial infection in lungs', Respirology (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 (2011) [E3]
|Show 1 more conference|
Grants and Funding
|Number of grants||4|
Click on a grant title below to expand the full details for that specific grant.
20171 grants / $738,768
Characterising the pro-inflammatory role of IL-36Â¿/IL-36R in pathogen-induced exacerbations of asthma and COPD$738,768
Funding body: NHMRC (National Health & Medical Research Council)
20162 grants / $342,314
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: Hunter Medical Research Institute
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
November 13, 2015
Dr Hock Tay has been awarded more than $314,000 in NHMRC Early Career Fellowships funding commencing in 2016 for his research in The role of long non-coding RNA in regulating lung immunity and inflammation.