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Dr Alan Hsu

Researcher

School of Medicine and Public Health (Immunology and Microbiology)

Career Summary

Biography

     Doctor Alan Hsu is a post-doctoral researcher at the Priority Research Centre for Asthma and Respiratory Diseases, and a member of Viruses, Infections/immunity, Vaccines and Asthma (VIVA) research group at Hunter Medical Research Institute. 

     His research focuses on the investigation of respiratory viral infection and human immunity, and why people with asthma or Chronic Obstuctive Pulmonary Disease (COPD) are more susceptible to infectious viruses such as influenza viruses, coronaviruses, and rhinovirus.

     Under the supervision of Prof. Peter Wark and Prof. Philip Hansbro he completed his PhD degree in 2011 and demonstrated that influenza viral entry into primary bronchial epithelial cells (pBECs) is not completely dependent on the long considered surface receptors, revealing other potential mechanisms involved in viral endocytosis. Innate antiviral responses are important in limiting viral infection and spread. He demonstrated that human influenza H3N2 is more effective in the suppression of antiviral responses including interferon (IFN)-beta and lambda responses compared to a low pathogenic avian H11N9 strain. This was the result of a more effective human influenza non-structural (NS) 1 protein compared to the avian NS1 protein. Nevertheless a low level constitutive release of IFN-beta was shown to counter-act part of the suppressive effect by the NS1 protein in an attempt to limit viral replication. High pathogenic avian H5N1 strain completely abolished this antiviral response with its NS1 protein. This demonstrates the importance of the antiviral responses to influenza infection, and also highlights the significance of NS1 proteins in the survival and fitness of the virus in human population. 

     His current research focuses on several areas of viral infection and innate immunity in people with asthma and chronic obstructive pulmonary disease (COPD). By using pBECs from healthy, asthmatic and COPD subjects, he is emplying various molecular biological techniques to investigate the molecular mechanisms underpinning the high susceptibility and severe infection outcomes in these individuals. These include innate immune dysregulations that result in exaggerated inflammatory responses and impaired antiviral responses to viral infections, including various strains and drug-resistant strain of influenza viruses, human coronaviruses, and rhinoviruses. He is also collaborating with World Health Organisation in the investigation of novel therapeutics against high pathogenic strains of influenza.

     This combination of biomedical approaches and the use of clinically relevant in vitro model will ultimately identify any potential and novel therapeutic targets not only for those with chronic airways diseases, but also for the general population against important emerging/re-emerging respiratory infectious diseases.

Research Expertise
Molecular biology, virology, and immunology

Teaching Expertise
Honour projects and RHD projects are available. Topics include respiratory viral infections (influenza, coronavirus, rhinovirus) and immune signallings and responses in people with asthma or chronic obstructive pulmonary disease (COPD). These may lead to identification of novel molecular therapeutic targets against important emerging/re-emerging viruses such as influenza or coronaviruses, or to treat those with asthma/COPD against viral infections.

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.

Collaborations
I am currently collaborating with Prof. Philip Hansbro's group in establishing the mechanisms of high susceptibility of COPD and asthmatics to influenza infection in a mouse model of COPD. 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.


Qualifications

  • PhD (Medicine), University of Newcastle

Keywords

  • Asthma
  • COPD
  • Coronavirus
  • Immunology
  • Influenza
  • Rhinovirus
  • Virology

Fields of Research

CodeDescriptionPercentage
060506Virology35
110203Respiratory Diseases30
110707Innate Immunity35

Professional Experience

UON Appointment

DatesTitleOrganisation / Department
1/01/2015 - 31/12/2015ResearcherUniversity of Newcastle
School of Medicine and Public Health
Australia
19/09/2009 - 13/11/2009Casual AcademicUniversity of Newcastle
School of Biomedical Sciences and Pharmacy
Australia

Academic appointment

DatesTitleOrganisation / Department
1/01/2013 - Membership - International Society for Interferon and Cytokine ResearchInternational Society for Interferon and Cytokine Research
United States
1/01/2007 - Membership - The Thoracic Society of Australia & New ZealandThe Thoracic Society of Australia & New Zealand
Australia
1/01/2007 - Membership - Australasian Society for ImmunologyAustralasian Society for Immunology
Australia

Awards

Recipient

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

Recognition

YearAward
2013Priority Research Centre Early Career Research Development Award
Unknown

Research Award

YearAward
2012Winner - 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.


Chapter (2 outputs)

YearCitationAltmetricsLink
2014Hsu 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]
Author URL
Co-authorsPeter Wark, Philip Hansbro
2014Hsu 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]
DOI10.1201/b16778-5Author URL
Co-authorsPeter Wark, Philip Hansbro

Journal article (8 outputs)

YearCitationAltmetricsLink
2015Hsu 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)
Author URL
Co-authorsPhilip Hansbro
2015Loo 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)
Author URL
Co-authorsPhilip Hansbro
2015Chen-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)
DOI10.1164/rccm.201501-0188OCAuthor URL
Co-authorsMalcolm Starkey, Philip Hansbro, Paul Foster, Peter Wark, Darryl Knight
2014Parsons 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 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.

DOI10.1111/cea.12218
CitationsScopus - 4Web of Science - 4
Co-authorsPeter Wark
2013Baines 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]
DOI10.1186/1465-9921-14-15Author URL
CitationsScopus - 7Web of Science - 8
Co-authorsPeter Gibson, Katherine Baines, Peter Wark
2012Hsu A, See HV, Hansbro PM, Wark PA, 'Innate immunity to influenza in chronic airways diseases', Respirology, 17 1166-1175 (2012) [C1]
CitationsScopus - 12Web of Science - 10
Co-authorsPeter Wark, Philip Hansbro
2012Hsu 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]
DOI10.1371/journal.pone.0032947
CitationsScopus - 18Web of Science - 20
Co-authorsPhilip Hansbro, Peter Wark
2011Hsu 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]
DOI10.1165/rcmb.2010-0157OC
CitationsScopus - 12Web of Science - 9
Co-authorsPhilip Hansbro, Peter Wark
Show 5 more journal articles

Conference (14 outputs)

YearCitationAltmetricsLink
2014Hsu 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]
DOI10.1016/j.cyto.2014.07.088Author URL
Co-authorsPhilip Hansbro, Peter Wark
2014Hsu 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]
DOI10.1016/j.cyto.2014.07.089Author URL
Co-authorsPeter Wark, Philip Hansbro
2014Starkey 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]
DOI10.1016/j.cyto2014.07.182Author URL
Co-authorsPeter Wark, Malcolm Starkey, Jay Horvat, Darryl Knight, Philip Hansbro, Paul Foster
2014Fathi 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]
DOI10.1111/resp.12263_3Author URL
Co-authorsLisa Wood, Peter Wark, Simon Keely
2014Hsu 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]
Author URL
Co-authorsPeter Wark, Philip Hansbro
2013Baines KJ, Simpson JL, Mcdonald VM, Hsu AC, Gibson PG, 'DIFFERENTIAL AIRWAY GENE EXPRESSION IN COPD', RESPIROLOGY (2013) [E3]
Author URL
Co-authorsJodie Simpson, Peter Gibson, Katherine Baines, Vanessa Mcdonald
2012Hsu 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-authorsPeter Wark, Philip Hansbro
2012Wark 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-authorsPeter Wark
2011Parsons 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-authorsPeter Wark
2011Wark PA, Parsons KS, Tooze MK, Hsu A, 'MDA5 is crucial inhibiting rhinovirus replication in primary bronchial epithelial cells', Respirology, Perth, WA (2011) [E3]
Co-authorsPeter Wark
2009Wark PA, Hsu A, Hansbro PM, 'Innate immune response of bronchial epithelial cells to infection with influenza', Journal of Immunology, Seattle, WASH. (2009) [E3]
Co-authorsPeter Wark, Philip Hansbro
2009Hsu 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-authorsPeter Wark, Philip Hansbro
2008Hsu 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]
DOI10.1111/j.1440-1843.2008.01252_13.x
Co-authorsPeter Wark
2008Hsu 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-authorsPeter Wark, Philip Hansbro
Show 11 more conferences
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Grants and Funding

Summary

Number of grants9
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 bodyJohn Hunter Hospital Charitable Trust Fund
Project TeamDoctor Alan Hsu, Conjoint Professor Peter Wark, Miss Kristy Parsons
SchemeResearch Grant
RoleLead
Funding Start2015
Funding Finish2015
GNoG1500012
Type Of FundingOther Public Sector - State
Category2OPS
UONY

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 bodyJohn Hunter Hospital Charitable Trust Fund
Project TeamDoctor Alan Hsu, Doctor Fatemeh Moheimani, Professor Darryl Knight, Conjoint Professor Peter Wark
SchemeResearch Grant
RoleLead
Funding Start2014
Funding Finish2014
GNoG1400435
Type Of FundingOther Public Sector - State
Category2OPS
UONY

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 bodyNHMRC (National Health & Medical Research Council)
Project TeamConjoint Professor Peter Wark, Doctor Alan Hsu, Doctor Katie Baines, Associate Professor Jodie Simpson, Conjoint Professor Peter Gibson, Ms Hayley See
SchemeEquipment Grant
RoleInvestigator
Funding Start2013
Funding Finish2013
GNoG1201180
Type Of FundingOther Public Sector - Commonwealth
Category2OPC
UONY

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 bodyJohn Hunter Hospital Charitable Trust Fund
Project TeamDoctor Alan Hsu, Conjoint Professor Peter Wark
SchemeResearch Grant
RoleLead
Funding Start2013
Funding Finish2013
GNoG1300711
Type Of FundingOther Public Sector - State
Category2OPS
UONY

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 bodyJohn Hunter Hospital Charitable Trust Fund
Project Team
SchemeResearch Grant
RoleLead
Funding Start2013
Funding Finish2014
GNo
Type Of FundingExternal
CategoryEXTE
UONY

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

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

Funding bodyNHMRC (National Health & Medical Research Council)
Project TeamLaureate 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
SchemeEquipment Grant
RoleInvestigator
Funding Start2013
Funding Finish2013
GNoG1201186
Type Of FundingOther Public Sector - Commonwealth
Category2OPC
UONY

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 bodyUniversity of Newcastle
Project TeamDoctor Alan Hsu
SchemeEarly Career Researcher Grant
RoleLead
Funding Start2013
Funding Finish2013
GNoG1300661
Type Of FundingInternal
CategoryINTE
UONY

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 bodyUniversity of Newcastle
Project TeamDoctor Fatemeh Moheimani, Professor Darryl Knight, Miss Kirsty Wark, Doctor Alan Hsu, Doctor Malcolm Starkey
SchemeEarly Career Researcher Grant
RoleInvestigator
Funding Start2013
Funding Finish2013
GNoG1301174
Type Of FundingInternal
CategoryINTE
UONY

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 bodyJohn Hunter Hospital Charitable Trust Fund
Project Team
SchemeResearch Grant
RoleLead
Funding Start2012
Funding Finish2013
GNo
Type Of FundingExternal
CategoryEXTE
UONY
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Research Supervision

Current Supervision

CommencedResearch Title / Program / Supervisor Type
2015Identification of Abnormalities in Innate Immunity in Asthma
General Medicine, Faculty of Health and Medicine
Co-Supervisor
2013The 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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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

Emailalan.hsu@newcastle.edu.au
Phone(02) 4042 0109
Fax(02) 4042 0022

Office

RoomRM 2109
BuildingLevel 2, West Wing, Hunter Medical Research Institute (HMRI)
LocationLot 1, Kookaburra Circuit, New Lambton Height, NSW 2305.

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