Dr Alan Hsu

Dr Alan Hsu

Researcher

School of Medicine and Public Health (Immunology and Microbiology)

Career Summary

Biography

     Dr. Alan Hsu is a post-doctoral researcher with research focuses on the mechanisms of influenza virus infections and human innate immunity in asthma and chronic obstructive pulmonary disease (COPD). People with asthma and COPD are highly susceptible to infection with influenza viruses and experience more severe symptoms with increased mortality. The mechanisms of this high susceptibility and severe infection outcome in asthma and COPD are unknown.  He discovered for the first time that bronchial epithelial cells from those with COPD were highly susceptible to more efficient influenza viral entry, regardless of strains/subtypes, and showed enhanced inflammatory but impaired antiviral responses to infection. The mechanisms underpinning these observations have led to the identification of novel therapeutic options for COPD and general public. The quality of this work is reflected on his success in winning a prestigious Ann Woolcock Young Investigator Award at the annual conference of Thoracic Society of Australia/New Zealand in 2012. This is followed by a patent application submission on the novel methods of inhibition of influenza virus infections. In 2013 he was awarded the Priority Research Centre Early Career Research Development Award from University of Newcastle for his overall research on influenza infection/immunity, and in asthma/COPD. 

     He has received several travel awards from societies including the Thoracic society of ANZ, and prestigious international immunology society ICIS and FIMSA to present his work. He has also been invited to Universiti Putra Malaysia for a special seminar on his current work on viral infections and immunity in 2015. 

Collaborations
     I am currently collaborating with Prof. Philip Hansbro's group in establishing the mechanisms of high susceptibility of COPD and asthmatics to infection in animal models. I am also working with Prof. Darryl Knight in cellular remodelling and repair in asthma. We are also collaborating with World Health Organisation (WHO) Collaborating Centre for Reference and Research on Influenza and CSIRO - Australian Animal Health Laboratory on high pathogenic influenza viruses. Internationally I am collaborating with Prof. Takashi Fujita at the Institute of Virus Research Kyoto University in elucidating the mechanisms of antiviral interferon responses during influenza viral infection. We are also working with Prof. James Mahony at McMaster University Canada on synthetic peptides against viral infection.

Administrative Expertise
     I am working as a member of Institution of Biosafety Committee, advisory to the Vice Chancellor. The committee assists the University to meet the legislative requirements of the Gene Technology Act 2000, as well as monitoring microbiological practice against Australian Standards and other aspects of biosafety related to biomedical and life sciences research.


Qualifications

  • PhD (Medicine), University of Newcastle

Keywords

  • Asthma
  • COPD
  • Coronavirus
  • Immunology
  • Influenza
  • Molecular Biology
  • Virology

Languages

  • English (Fluent)

Fields of Research

Code Description Percentage
060506 Virology 35
110203 Respiratory Diseases 30
110707 Innate Immunity 35

Professional Experience

UON Appointment

Title Organisation / Department
Researcher University of Newcastle
School of Medicine and Public Health
Australia

Academic appointment

Dates Title Organisation / Department
1/01/2013 -  Membership - International Society for Interferon and Cytokine Research International Society for Interferon and Cytokine Research
United States
1/01/2007 -  Membership - The Thoracic Society of Australia & New Zealand The Thoracic Society of Australia & New Zealand
Australia
1/01/2007 -  Membership - Australasian Society for Immunology Australasian Society for Immunology
Australia

Awards

Recipient

Year Award
2015 Federation of Immunological Societies Asia-Oceania (FIMSA) Travel fellowship
Unknown
2014 The Milstein Travel Awards
International Cytokine and Interferon Society
2012 TSANZ Travel Award
Thoracic Society of Australia and New Zealand
2009 TSANZ Travel Award
Thoracic Society of Australia and New Zealand

Recognition

Year Award
2013 Priority Research Centre Early Career Research Development Award
Unknown

Research Award

Year Award
2012 Winner - Ann Woolcock Young Investigator Award
Thoracic Society of Australia and New Zealand
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Publications

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

Highlighted Publications

Year Citation Altmetrics Link
2015 Chen-Yu Hsu A, Starkey MR, Hanish I, Parsons K, Haw TJ, Howland LJ, et al., 'Targeting PI3K-p110a Suppresses Influenza Virus Infection in Chronic Obstructive Pulmonary Disease.', Am J Respir Crit Care Med, 191 1012-1023 (2015)
DOI 10.1164/rccm.201501-0188OC
Co-authors Malcolm Starkey, Philip Hansbro, Peter Wark, Paul Foster, Darryl Knight

Chapter (2 outputs)

Year Citation Altmetrics Link
2014 Hsu A, Zhong H, Hansbro P, Wark P, 'Innate Immunity in the Airways to Respiratory Viruses', Virology II - Advanced Issues, iConcept Press, Hong Kong 1-32 (2014) [B1]
Co-authors Peter Wark, Philip Hansbro
2014 Hsu A, Loo S, Fathi Aghdam F, Parsons K, Hansbro P, Wark P, 'Airway Epithelial and Early Innate Immune Responses to Virus Infections', Human Respiratory Viral Infections, CRC Press, Boca Raton, FL 29-44 (2014) [B1]
DOI 10.1201/b16778-5
Co-authors Peter Wark, Philip Hansbro

Journal article (8 outputs)

Year Citation Altmetrics Link
2015 Hsu A, Parsons K, Hansbro P, Wark P, 'ENHANCED PI3K ACTIVITY LEADS TO DECREASED INTERFERON-beta RESPONSE TO INFLUENZA INFECTION IN COPD', RESPIROLOGY, 20 45-45 (2015)
Co-authors Philip Hansbro
2015 Loo S, Hsu A, Hansbro P, Wark P, 'THE ROLE OF PI3 KINASE IN INFLUENZA H1N1 AND RHINOVIRUS VIRAL ENTRY INTO PRIMARY BRONCHIAL EPITHELIAL CELLS', RESPIROLOGY, 20 128-128 (2015)
Co-authors Philip Hansbro
2015 Chen-Yu Hsu A, Starkey MR, Hanish I, Parsons K, Haw TJ, Howland LJ, et al., 'Targeting PI3K-p110a Suppresses Influenza Virus Infection in Chronic Obstructive Pulmonary Disease.', Am J Respir Crit Care Med, 191 1012-1023 (2015)
DOI 10.1164/rccm.201501-0188OC
Co-authors Malcolm Starkey, Philip Hansbro, Peter Wark, Paul Foster, Darryl Knight
2014 Parsons KS, Hsu AC, Wark PAB, 'TLR3 and MDA5 signalling, although not expression, is impaired in asthmatic epithelial cells in response to rhinovirus infection', Clinical and Experimental Allergy, 44 91-101 (2014) [C1]

Summary: Background: Rhinoviruses (RV) are the most common acute triggers of asthma, and airway epithelial cells are the primary site of infection. Asthmatic bronchial epithelial ... [more]

Summary: Background: Rhinoviruses (RV) are the most common acute triggers of asthma, and airway epithelial cells are the primary site of infection. Asthmatic bronchial epithelial cells (BECs) have been found to have impaired innate immune responses to RV. RV entry and replication is recognized by pathogen recognition receptors (PRRs), specifically toll-like receptor (TLR)3 and the RNA helicases; retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). Objective: Our aim was to assess the relative importance of these PRRs in primary bronchial epithelial cells (pBEC) from healthy controls and asthmatics following RV infection and determine whether deficient innate immune responses in asthmatic pBECs were due to abnormal signalling via these PRRs. Methods: The expression patterns and roles of TLR3 and MDA5 were investigated using siRNA knock-down, with subsequent RV1B infection in pBECs from each patient group. We also used BX795, a specific inhibitor of TBK1 and IKKi. Results: Asthmatic pBECs had significantly reduced release of IL-6, CXCL-8 and IFN-¿ in response to RV1B infection compared with healthy pBECs. In healthy pBECs, siMDA5, siTLR3 and BX795 all reduced release of IL-6, CXCL-10 and IFN-¿ to infection. In contrast, in asthmatic pBECs where responses were already reduced, there was no further reduction in IL-6 and IFN-¿, although there was in CXCL-10. Conclusion and Clinical Relevance: Impaired antiviral responses in asthmatic pBECs are not due to deficient expression of PRRs; MDA5 and TLR3, but an inability to later activate types I and III interferon immune responses to RV infection, potentially increasing susceptibility to the effects of RV infection. © 2013 John Wiley & Sons Ltd.

DOI 10.1111/cea.12218
Citations Scopus - 5Web of Science - 4
Co-authors Peter Wark
2013 Baines KJ, Hsu AC-Y, Tooze M, Gunawardhana LP, Gibson PG, Wark PAB, 'Novel immune genes associated with excessive inflammatory and antiviral responses to rhinovirus in COPD', RESPIRATORY RESEARCH, 14 (2013) [C1]
DOI 10.1186/1465-9921-14-15
Citations Scopus - 7Web of Science - 9
Co-authors Peter Gibson, Katherine Baines, Peter Wark
2012 Hsu A, See HV, Hansbro PM, Wark PA, 'Innate immunity to influenza in chronic airways diseases', Respirology, 17 1166-1175 (2012) [C1]
Citations Scopus - 12Web of Science - 10
Co-authors Peter Wark, Philip Hansbro
2012 Hsu A, Parsons KS, Barr I, Lowther S, Middleton D, Hansbro PM, Wark PA, 'Critical role of constitutive type I interferon response in bronchial epithelial cell to influenza infection', PLoS One, 7 e32947 (2012) [C1]
DOI 10.1371/journal.pone.0032947
Citations Scopus - 18Web of Science - 20
Co-authors Philip Hansbro, Peter Wark
2011 Hsu A, Barr I, Hansbro PM, Wark PA, 'Human influenza is more effective than Avian influenza at antiviral suppression in airway cells', American Journal of Respiratory Cell and Molecular Biology, 44 906-913 (2011) [C1]
DOI 10.1165/rcmb.2010-0157OC
Citations Scopus - 12Web of Science - 9
Co-authors Philip Hansbro, Peter Wark
Show 5 more journal articles

Conference (14 outputs)

Year Citation Altmetrics Link
2014 Hsu A, Parsons K, Fujita T, Hansbro P, Wark P, 'Critical role of PKR in antiviral stress granule and IFN-beta enhanceosome formation, and is impaired in chronic obstructive pulmonary disease', CYTOKINE, Melbourne, AUSTRALIA (2014) [E3]
DOI 10.1016/j.cyto.2014.07.088
Co-authors Philip Hansbro, Peter Wark
2014 Hsu A, Parsons K, Hansbro P, Wark P, 'Enhanced PI3K activity leads to decreased IFN-beta response to influenza infection in chronic obstructive pulmonary disease', CYTOKINE, Melbourne, AUSTRALIA (2014) [E3]
DOI 10.1016/j.cyto.2014.07.089
Co-authors Peter Wark, Philip Hansbro
2014 Starkey M, Hanish I, Dua K, Nair P, Haw T, Hsu A, et al., 'Interleukin-13 predisposes mice to more severe influenza infection by suppressing interferon responses and activating microRNA-21/PI3K', CYTOKINE, Melbourne, AUSTRALIA (2014) [E3]
DOI 10.1016/j.cyto2014.07.182
Co-authors Jay Horvat, Malcolm Starkey, Peter Wark, Darryl Knight, Philip Hansbro, Paul Foster
2014 Fathi F, Hsu A, Parsons K, Keely S, Wood L, Wark P, 'OXIDATIVE STRESS IMPAIRS MITOCHONDRIAL FUNCTION AND LEADS TO DEFICIENT ANTIVIRAL RESPONSES IN PRIMARY BRONCHIAL EPITHELIAL CELLS', RESPIROLOGY (2014) [E3]
DOI 10.1111/resp.12263_3
Co-authors Lisa Wood, Peter Wark, Simon Keely
2014 Hsu A, Parsons K, Hansbro P, Wark P, Wark P, 'IMPAIRED FORMATION OF ANTIVIRAL STRESS GRANULE AND INTERFERON-BETA ENHANCEOSOME LEADS TO REDUCED ANTIVIRAL RESPONSES TO INFLUENZA IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE', RESPIROLOGY (2014) [E3]
Co-authors Peter Wark, Philip Hansbro
2013 Baines KJ, Simpson JL, Mcdonald VM, Hsu AC, Gibson PG, 'DIFFERENTIAL AIRWAY GENE EXPRESSION IN COPD', RESPIROLOGY (2013) [E3]
Co-authors Peter Gibson, Katherine Baines, Jodie Simpson, Vanessa Mcdonald
2012 Hsu A, Parsons KS, Barr I, Hansbro PM, Wark PA, 'Deficient antiviral responses to influenza in primary bronchial epithelial cells of chronic obstructive pulmonary disease', Respirology, Canberra, ACT (2012) [E3]
Co-authors Peter Wark, Philip Hansbro
2012 Wark PA, Tooze MK, Hsu A, Parsons KS, 'Silencing of MDA5 and TLR3 does not reduce innate immune responses to rhinovirus in defective asthmatic bronchial epithelial cells', Respirology, Canberra, ACT (2012) [E3]
Co-authors Peter Wark
2011 Parsons KS, Tooze MK, Hsu A, Wark PA, 'Oxidative stress induces mitochondrial dusfunction in airway epithelial cells and impairs response to rhinovirus', Respirology, Perth, WA (2011) [E3]
Co-authors Peter Wark
2011 Wark PA, Parsons KS, Tooze MK, Hsu A, 'MDA5 is crucial inhibiting rhinovirus replication in primary bronchial epithelial cells', Respirology, Perth, WA (2011) [E3]
Co-authors Peter Wark
2009 Wark PA, Hsu A, Hansbro PM, 'Innate immune response of bronchial epithelial cells to infection with influenza', Journal of Immunology, Seattle, WASH. (2009) [E3]
Co-authors Peter Wark, Philip Hansbro
2009 Hsu A, Hansbro PM, Barr I, Wark PA, 'Innate immune response of bronchial epithelial cells to human and avian influenza virus', Respirology, Darwin, NT (2009) [E3]
Co-authors Peter Wark, Philip Hansbro
2008 Hsu A, Grissell TV, Wark PA, 'Distribution of SAa2,6GAL and SAa2,3GAL linked receptors in human respiratory tract and influenza virus replication', Respirology, Melbourne, VIC (2008) [E3]
DOI 10.1111/j.1440-1843.2008.01252_13.x
Co-authors Peter Wark
2008 Hsu A, Hansbro PM, Wark PA, 'Innate immune response of bronchial epithelial cells to human and avian influenza virus', The 4th Congress of the Federation of Immunology Societies of Asia-Oceania: Conference Program, Taipei, Taiwan (2008) [E3]
Co-authors Peter Wark, Philip Hansbro
Show 11 more conferences
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Grants and Funding

Summary

Number of grants 9
Total funding $185,354

Click on a grant title below to expand the full details for that specific grant.


20151 grants / $25,222

Enhanced oxidative stress impairs mitochondrial function and antiviral responses to rhinovirus infection in asthma and chronic obstructive pulmonary disease$25,222

Funding body: John Hunter Hospital Charitable Trust Fund

Funding body John Hunter Hospital Charitable Trust Fund
Project Team Doctor Alan Hsu, Conjoint Professor Peter Wark, Miss Kristy Parsons
Scheme Research Grant
Role Lead
Funding Start 2015
Funding Finish 2015
GNo G1500012
Type Of Funding Other Public Sector - State
Category 2OPS
UON Y

20141 grants / $27,512

Mechanisms of dysregulated antiviral signallings to influenza infection in chronic obstructive pulmonary disease$27,512

Funding body: John Hunter Hospital Charitable Trust Fund

Funding body John Hunter Hospital Charitable Trust Fund
Project Team Doctor Alan Hsu, Doctor Fatemeh Moheimani, Professor Darryl Knight, Conjoint Professor Peter Wark
Scheme Research Grant
Role Lead
Funding Start 2014
Funding Finish 2014
GNo G1400435
Type Of Funding Other Public Sector - State
Category 2OPS
UON Y

20136 grants / $112,620

BD FACSCanto II Violet Laser (405nm) upgrade including Trigon and 2 photomultiplier tubes (PMTs)$25,000

Funding body: NHMRC (National Health & Medical Research Council)

Funding body NHMRC (National Health & Medical Research Council)
Project Team Conjoint Professor Peter Wark, Doctor Alan Hsu, Doctor Katie Baines, Associate Professor Jodie Simpson, Conjoint Professor Peter Gibson, Ms Hayley See
Scheme Equipment Grant
Role Investigator
Funding Start 2013
Funding Finish 2013
GNo G1201180
Type Of Funding Other Public Sector - Commonwealth
Category 2OPC
UON Y

Mechanisms of impaired antiviral interferon response to influenza infection in primary bronchial epithelial cells from chronic obstructive pulmonary disease$23,810

Funding body: John Hunter Hospital Charitable Trust Fund

Funding body John Hunter Hospital Charitable Trust Fund
Project Team Doctor Alan Hsu, Conjoint Professor Peter Wark
Scheme Research Grant
Role Lead
Funding Start 2013
Funding Finish 2013
GNo G1300711
Type Of Funding Other Public Sector - State
Category 2OPS
UON Y

Mechanisms of impaired antiviral interferon response to influenza infection in primary bronchial epithelial cells from chronic obstructive pulmonary disease$23,810

People with chronic obstructive pulmonary disease (COPD) are particularly susceptible to influenza infection, leading to more severe symptoms with increased mortality, especially during influenza pandemics such as the 2009 swine influenza pandemic. The mechanisms that lead to increased susceptibility to viral infection and the poor outcomes that occur in COPD though are unclear. We have identified for the first time that primary bronchial epithelial cells (pBECs) from COPD subjects have impaired innate antiviral responses to influenza infection, leading to higher viral replication. The molecular mechanisms underpinning this deficient antiviral response however is still unclear. This project investigate the underlying molecular mechanisms of impaired antiviral responses to influenza in those with COPD.

Funding body: John Hunter Hospital Charitable Trust Fund

Funding body John Hunter Hospital Charitable Trust Fund
Project Team
Scheme Research Grant
Role Lead
Funding Start 2013
Funding Finish 2014
GNo
Type Of Funding External
Category EXTE
UON Y

DP73 Digital colour and monochrome camera + cellSens software + Xcite120 fluorescence lamp illuminator$20,000

Funding body: NHMRC (National Health & Medical Research Council)

Funding body NHMRC (National Health & Medical Research Council)
Project Team Laureate Professor Paul Foster, Doctor Alan Hsu, Professor Phil Hansbro, Professor Joerg Mattes, Doctor Katie Baines, Associate Professor Jodie Simpson, Professor Rakesh Kumar, Doctor Nicole Hansbro, Doctor Steven Maltby, Doctor Ming Yang, Doctor Gerard Kaiko, Doctor Jay Horvat, Doctor Simon Keely, Doctor Andrew Jarnicki, Doctor Michael Fricker
Scheme Equipment Grant
Role Investigator
Funding Start 2013
Funding Finish 2013
GNo G1201186
Type Of Funding Other Public Sector - Commonwealth
Category 2OPC
UON Y

Mechanisms of increased respiratory viral entry into primary bronchial epithelial cells from people with chronic obstructive pulmonary disease$10,000

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Doctor Alan Hsu
Scheme Early Career Researcher Grant
Role Lead
Funding Start 2013
Funding Finish 2013
GNo G1300661
Type Of Funding Internal
Category INTE
UON Y

Role of the transcriptional co-activator p300 in resetting epithelial differentiation: A potential pathway involved in asthma prevention and therapy$10,000

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Doctor Fatemeh Moheimani, Professor Darryl Knight, Miss Kirsty Wark, Doctor Alan Hsu, Doctor Malcolm Starkey
Scheme Early Career Researcher Grant
Role Investigator
Funding Start 2013
Funding Finish 2013
GNo G1301174
Type Of Funding Internal
Category INTE
UON Y

20121 grants / $20,000

Molecular mechanism of high susceptibility to influenza infection in people with chronic obstructive pulmonary disease$20,000

People with chronic obstructive pulmonary disease (COPD) are particularly susceptible to influenza infection, leading to more severe symptoms with increased risk of death, especially during influenza pandemics such as the 2009 swine influenza pandemic. The mechanisms that lead to increased susceptibility to influenza and the poor outcomes that occur in COPD are unclear. We have identified that influenza viruses are able to enter primary bronchial epithelial cells (pBECs) from COPD subjects more efficiently than into that of healthy subjects. COPD pBECs were also unable to mount robust antiviral defences against influenza infection, resulting in higher viral replication. These findings were then confirmed in our mice model of COPD. However the specific mechanism(s) underlying this enhanced viral entry and the poor innate antiviral responses in COPD is still unclear. Phosphatidylinositol-3-kinase (PI3K), a ubiquitous metabolic signalling pathway, that was recently found to be critical for influenza entry. We then determined that COPD pBECs had enhanced baseline expression of PI3K and that this closely correlated with increased viral entry and reduced antiviral responses compared to healthy control pBECs. These findings provide important insight in the high susceptibility to influenza in COPD, that may reveal novel therapeutic options for influenza infection in this study. We have previously determined, using pBECs from healthy volunteers, that human influenza virus is more effective in suppressing human antiviral responses than avian influenza virus, and demonstrated the importance of a key influenza virulence factor in host immune suppression. In this study I will build on my current knowledge in the immunology field and identify the abnormalities that exist in COPD pBECs. This experimental approach places me in a strong position in providing further insight into the mechanism of influenza infection in COPD pBECs and to assess the efficacy of novel potential therapeutic options not only for preparedness of future influenza pandemics, but also for those with chronic airways diseases such as COPD.

Funding body: John Hunter Hospital Charitable Trust Fund

Funding body John Hunter Hospital Charitable Trust Fund
Project Team
Scheme Research Grant
Role Lead
Funding Start 2012
Funding Finish 2013
GNo
Type Of Funding External
Category EXTE
UON Y
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Research Supervision

Current Supervision

Commenced Research Title / Program / Supervisor Type
2015 Identification of Abnormalities in Innate Immunity in Asthma
General Medicine, Faculty of Health and Medicine
Co-Supervisor
2013 The Role of the PI3K Signalling Pathway in the Innate Antiviral Response of Airway Epithelial Cells
General Medicine, Faculty of Health and Medicine
Co-Supervisor
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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 16
Canada 1
Japan 1
Malaysia 1
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Dr Alan Hsu

Position

Researcher
Centre for Asthma and Respiratory Diseases
School of Medicine and Public Health
Faculty of Health and Medicine

Focus area

Immunology and Microbiology

Contact Details

Email alan.hsu@newcastle.edu.au
Phone (02) 4042 0109
Fax (02) 4042 0022
Link Twitter

Office

Room RM 2109
Building Level 2, West Wing, Hunter Medical Research Institute (HMRI)
Location Lot 1, Kookaburra Circuit, New Lambton Height, NSW 2305.

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