Dr Jason Girkin

Dr Jason Girkin

Associate Lecturer

School of Biomedical Sciences and Pharmacy

Career Summary

Biography

Jason complete a first class research honours project in 2011 in the Bachelor of Biomedical Sciences and Pharmacy, focusing on the role of early life rhinovirus infections and patter recognition receptors in the development of asthma. After honours, Jason went on to PhD studies in Immunology and Microbiology. His thesis focused on the role of rhinovirus infection and novel molecular signalling pathways in asthma exacerbations.

Qualifications

  • Doctor of Philosophy, University of Newcastle
  • Bachelor of Biomedical Sciences, University of Newcastle
  • Bachelor of Biomedical Sciences (Hons), University of Newcastle

Keywords

  • Asthma
  • Innate Immunity
  • Rhinovirus

Fields of Research

Code Description Percentage
110799 Immunology not elsewhere classified 100

Professional Experience

UON Appointment

Title Organisation / Department
Associate Lecturer University of Newcastle
School of Biomedical Sciences and Pharmacy
Australia

Teaching

Code Course Role Duration
MEDI1101B Year 1 JMP MD PBL Tutorials
Faculty of Health and Medicine, University of Newcastle

Overview of the Immune System Functino

Introduction to microbes, microbiota and infections

Associate Lecturer 27/03/2019 - 28/03/2019
MEDI2101A Clinical Sciences, Scholarship and Practice 2 Part A
Faculty of Health and Medicine, University of Newcastle
Pathogenesis of autoimmune processes in the nervous system
Associate Lecturer - Biomedical Sciences Content 24/05/2019 - 25/05/2019
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Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Journal article (5 outputs)

Year Citation Altmetrics Link
2018 Singanayagam A, Glanville N, Girkin JL, Ching YM, Marcellini A, Porter JD, et al., 'Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations', NATURE COMMUNICATIONS, 9 (2018) [C1]
DOI 10.1038/s41467-018-04574-1
Citations Scopus - 9Web of Science - 8
Co-authors Andrew Reid, Punnam Veerati, Darryl Knight, Nathan Bartlett, Peter Wark, Christopher Grainge
2017 Girkin JL, Hatchwell LM, Collison AM, Starkey MR, Hansbro PM, Yagita H, et al., 'TRAIL signaling is proinflammatory and proviral in a murine model of rhinovirus 1B infection', American Journal of Physiology - Lung Cellular and Molecular Physiology, 312 L89-L99 (2017) [C1]

© 2017 the American Physiological Society. The aim of this study is to elucidate the role of TRAIL during rhinovirus (RV) infection in vivo. Naïve wild-type and tumor necrosis fac... [more]

© 2017 the American Physiological Society. The aim of this study is to elucidate the role of TRAIL during rhinovirus (RV) infection in vivo. Naïve wild-type and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-deficient (Tnfsf10-/-) BALB/c mice were infected intranasally with RV1B. In separate experiments, Tnfsf10-/-mice were sensitized and challenged via the airway route with house dust mite (HDM) to induce allergic airways disease and then challenged with RVIB or UV-RVIB. Airway hyperreactivity (AHR) was invasively assessed as total airways resistance in response to increasing methacholine challenge and inflammation was assessed in bronchoalveolar lavage fluid at multiple time points postinfection. Chemokines were quantified by ELISA of whole lung lysates and viral load was determined by quantitative RT-PCR and tissue culture infective dose (TCID50). Human airway epithelial cells (BEAS2B) were infected with RV1B and stimulated with recombinant TRAIL or neutralizing anti-TRAIL antibodies and viral titer assessed by TCID50. HDM-challenged Tnfsf10-/-mice were protected against RV-induced AHR and had suppressed cellular infiltration in the airways upon RV infection. Chemokine C-X-C-motif ligand 2 (CXCL2) production was suppressed in naïve Tnfsf10-/-mice infected with RV1B, with less RV1B detected 24 h postinfection. This was associated with reduced apoptotic cell death and a reduction of interferon (IFN)-¿2/3 but not IFN-a or IFN-ß. TRAIL stimulation increased, whereas anti-TRAIL antibodies reduced viral replication in RV1B-infected BEAS2B cells in vitro. In conclusion, TRAIL promotes RV-induced AHR, inflammation and RV1B replication, implicating this molecule and its downstream signaling pathways as a possible target for the amelioration of RV1B-induced allergic and nonallergic lung inflammation and AHR.

DOI 10.1152/ajplung.00200.2016
Citations Scopus - 8Web of Science - 7
Co-authors Paul Foster, Philip Hansbro, Malcolm Starkey, Adam Collison, Joerg Mattes
2015 Hatchwell L, Collison A, Girkin J, Parsons K, Li J, Zhang J, et al., 'Toll-like receptor 7 governs interferon and inflammatory responses to rhinovirus and is suppressed by IL-5-induced lung eosinophilia', Thorax, (2015) [C1]

© 2015 BMJ Publishing Group Ltd & British Thoracic Society.Background Asthma exacerbations represent a significant disease burden and are commonly caused by rhinovirus (RV), w... [more]

© 2015 BMJ Publishing Group Ltd & British Thoracic Society.Background Asthma exacerbations represent a significant disease burden and are commonly caused by rhinovirus (RV), which is sensed by Toll-like receptors (TLR) such as TLR7. Some asthmatics have impaired interferon (IFN) responses to RV, but the underlying mechanisms of this clinically relevant observation are poorly understood. Objectives To investigate the importance of intact TLR7 signalling in vivo during RV exacerbation using mouse models of house dust mite (HDM)-induced allergic airways disease exacerbated by a superimposed RV infection. Methods Wild-type and TLR7-deficient (Tlr7<sup>-/-</sup>) BALB/c mice were intranasally sensitised and challenged with HDM prior to infection with RV1B. In some experiments, mice were administered recombinant IFN or adoptively transferred with plasmacytoid dendritic cells (pDC). Results Allergic Tlr7<sup>-/-</sup> mice displayed impaired IFN release upon RV1B infection, increased virus replication and exaggerated eosinophilic inflammation and airways hyper reactivity. Treatment with exogenous IFN or adoptive transfer of TLR7-competent pDCs blocked these exaggerated inflammatory responses and boosted IFN? release in the absence of host TLR7 signalling. TLR7 expression in the lungs was suppressed by allergic inflammation and by interleukin (IL)-5-induced eosinophilia in the absence of allergy. Subjects with moderate-to-severe asthma and eosinophilic but not neutrophilic airways inflammation, despite inhaled steroids, showed reduced TLR7 and IFN?2/3 expression in endobronchial biopsies. Furthermore, TLR7 expression inversely correlated with percentage of sputum eosinophils. Conclusions This implicates IL-5-induced airways eosinophilia as a negative regulator of TLR7 expression and antiviral responses, which provides a molecular mechanism underpinning the effect of eosinophil-targeting treatments for the prevention of asthma exacerbations.

DOI 10.1136/thoraxjnl-2014-205465
Citations Scopus - 39Web of Science - 38
Co-authors Peter Wark, Darryl Knight, Joerg Mattes, Paul Foster, Nathan Bartlett, Adam Collison
2015 Girkin J, Hatchwell L, Foster P, Johnston SL, Bartlett N, Collison A, Mattes J, 'CCL7 and IRF-7 mediate hallmark inflammatory and IFN responses following rhinovirus 1B infection', Journal of Immunology, 194 4924-4930 (2015) [C1]

Copyright © 2015 by The American Association of Immunologists, Inc. Rhinovirus (RV) infections are common and have the potential to exacerbate asthma. We have determined the lung ... [more]

Copyright © 2015 by The American Association of Immunologists, Inc. Rhinovirus (RV) infections are common and have the potential to exacerbate asthma. We have determined the lung transcriptome in RV strain 1B-infected naive BALB/c mice (nonallergic) and identified CCL7 and IFN regulatory factor (IRF)-7 among the most upregulated mRNA transcripts in the lung. To investigate their roles we employed anti-CCL7 Abs and an IRF-7-targeting small interfering RNA in vivo. Neutralizing CCL7 or inhibiting IRF-7 limited neutrophil and macrophage influx and IFN responses in nonallergic mice. Neutralizing CCL7 also reduced activation of NF-¿B p65 and p50 subunits, as well as airway hyperreactivity (AHR) in nonallergic mice. However, neither NF-¿B subunit activation nor AHR was abolished with infection of allergic mice after neutralizing CCL7, despite a reduction in the number of neutrophils, macrophages, and eosinophils. IRF-7 small interfering RNA primarily suppressed IFN-a and IFN-b levels during infection of allergic mice. Our data highlight a pivotal role of CCL7 and IRF-7 in RV-induced inflammation and IFN responses and link NF-¿B signaling to the development of AHR.

DOI 10.4049/jimmunol.1401362
Citations Scopus - 20Web of Science - 21
Co-authors Nathan Bartlett, Paul Foster, Joerg Mattes, Adam Collison
2014 Hatchwell L, Girkin J, Morten M, Collison A, Mattes J, Foster PS, et al., 'Salmeterol attenuates chemotactic responses in rhinovirus-induced exacerbation of allergic airways disease by modulating protein phosphatase 2A', Journal of Allergy and Clinical Immunology, (2014) [C1]

Background: ß-Agonists are used for relief and control of asthma symptoms by reversing bronchoconstriction. They might also have anti-inflammatory properties, but the underpinning... [more]

Background: ß-Agonists are used for relief and control of asthma symptoms by reversing bronchoconstriction. They might also have anti-inflammatory properties, but the underpinning mechanisms remain poorly understood. Recently, a direct interaction between formoterol and protein phosphatase 2A (PP2A) has been described in¿vitro. Objective: We sought to elucidate the molecular mechanisms by which ß-agonists exert anti-inflammatory effects in allergen-driven and rhinovirus 1B-exacerbated allergic airways disease (AAD). Methods: Mice were sensitized and then challenged with house dust mite to induce AAD while receiving treatment with salmeterol, formoterol, or salbutamol. Mice were also infected with rhinovirus 1B to exacerbate lung inflammation and therapeutically administered salmeterol, dexamethasone, or the PP2A-activating drug (S)-2-amino-4-(4-[heptyloxy]phenyl)-2-methylbutan-1-ol (AAL[S]). Results: Systemic or intranasal administration of salmeterol protected against the development of allergen- and rhinovirus-induced airway hyperreactivity and decreased eosinophil recruitment to the lungs as effectively as dexamethasone. Formoterol and salbutamol also showed anti-inflammatory properties. Salmeterol, but not dexamethasone, increased PP2A activity, which reduced CCL11, CCL20, and CXCL2 expression and reduced levels of phosphorylated extracellular signal-regulated kinase 1 and active nuclear factor ¿B subunits in the lungs. The anti-inflammatory effect of salmeterol was blocked by targeting the catalytic subunit of PP2A with small RNA interference. Conversely, increasing PP2A activity with AAL(S) abolished rhinovirus-induced airway hyperreactivity, eosinophil influx, and CCL11, CCL20, and CXCL2 expression. Salmeterol also directly activated immunoprecipitated PP2A in¿vitro isolated from human airway epithelial cells. Conclusions: Salmeterol exerts anti-inflammatory effects by increasing PP2A activity in AAD and rhinovirus-induced lung inflammation, which might potentially account for some of its clinical benefits. © 2013 American Academy of Allergy, Asthma & Immunology.

DOI 10.1016/j.jaci.2013.11.014
Citations Scopus - 24Web of Science - 23
Co-authors Paul Foster, Nikki Verrills, Adam Collison, Matt Dun, Joerg Mattes
Show 2 more journal articles

Conference (7 outputs)

Year Citation Altmetrics Link
2019 Williams T, Girkin J, Nichol K, Knight D, Alton K, Shimkets R, Bartlett N, 'IL-25 BLOCKADE AUGMENTS EPITHELIAL ANTIVIRAL IMMUNITY DURING RHINOVIRUS INFECTION', RESPIROLOGY (2019)
Co-authors Nathan Bartlett
2018 Bartlett N, Girkin J, Williams T, Vincent T, Jackson C, Alton K, Shimkets R, 'ABM125 Anti-IL-25 Antibody Pre-Clinical Development for Viral Asthma Exacerbations Identifies IL-25 Mediated Regulation of Type-2-and Anti-Viral Immunity', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, San Diego, CA (2018)
Co-authors Nathan Bartlett
2018 Bartlett NW, Girkin J, Wong C, Deliyannis G, Zeng W, Demaison C, Jackson DC, 'Upper Airway TLR2 Immune Modulators Prime Broad Respiratory Immunity Against Rhinovirus and Influenza Infection and Inhibit Subsequent Lung Inflammation', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, San Diego, CA (2018)
Co-authors Nathan Bartlett
2014 Collison A, Hatchwell L, Girkin J, Parsons K, Li J, Zhang J, et al., 'Late-breaking abstract: IL-5-induced airways eosinophilia as a negative regulator of TLR7 expression may impair the interferon response to rhinovirus in allergic airways', EUROPEAN RESPIRATORY JOURNAL (2014)
Co-authors Peter Wark, Adam Collison, Nathan Bartlett, Paul Foster, Joerg Mattes
2014 Collison A, Hatchwell L, Girkin J, Li J, Parsons K, Bartlett N, et al., 'REDUCED TLR7 EXPRESSION MAY UNDERPIN IMPAIRED RESPONSE TO VIRAL INFECTION IN ASTHMA', RESPIROLOGY (2014) [E3]
DOI 10.1111/resp.12263_5
Co-authors Adam Collison, Joerg Mattes, Paul Foster, Peter Wark
2014 Girkin J, Sokulsky L, Hatchwell L, Starkey M, Collison A, Hansbro P, Mattes J, 'IDENTIFICATION OF A NOVEL INTERLEUKIN-13 SIGNALLING PATHWAY', RESPIROLOGY (2014) [E3]
Co-authors Malcolm Starkey, Adam Collison, Philip Hansbro, Joerg Mattes
2013 Girkin J, Hatchwell L, Foster PS, Johnston SL, Collison A, Mattes J, 'SALMETEROL ATTENUATES CHEMOTAXIS IN RHINOVIRUS-INDUCED EXACERBATION OF ASTHMA VIA MODULATION OF PP2A', RESPIROLOGY (2013) [E3]
Co-authors Joerg Mattes, Paul Foster, Adam Collison
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Research Collaborations

The map is a representation of a researchers co-authorship with collaborators across the globe. The map displays the number of publications against a country, where there is at least one co-author based in that country. Data is sourced from the University of Newcastle research publication management system (NURO) and may not fully represent the authors complete body of work.

Country Count of Publications
Australia 11
United Kingdom 6
United States 2
China 1
Japan 1
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Dr Jason Girkin

Position

Associate Lecturer
Viral Immunology and Respiratory Disease, Priority Research Centre for Healthy Lungs
School of Biomedical Sciences and Pharmacy
Faculty of Health and Medicine

Contact Details

Email jason.girkin@newcastle.edu.au
Phone (02) 40420847
Links Twitter
Research Networks

Office

Building HMRI -Hunter Medical Research Institute
Location Hunter Medical Research Institute

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