Dr Alan Hsu

Biography

I am managing the laboratory of the Priority Research Centre for Asthma and Respiratory Diseases (Viruses, Infections/immunity, Vaccines and Asthma at Hunter Medical Research Institute).

I am also a post-doctoral researcher whom has developed interests in influenza viruses and rhinoviruses, and its interaction with human immune system. Under the supervision of A/Prof. Peter Wark and Prof. Phil Hansbro I completed my PhD degree in December 2010 and established by using in vitro primary bronchial epithelial cells (pBECs) that influenza viral entry into pBECs is not completely dependent on the long considered surface receptors on the host cell surface, revealing other potential receptors involved in viral endocytosis. Innate antiviral responses, being a critical first line of defense that determines the outcome of infection, were impaired in pBECs with human influenza infection compared to that with a low pathogenic avian influenza infection. This differential response was further shown to be attributed to a more effective immune suppressive viral NS1 protein encoded by the human influenza. I have further demonstrated that the highly pathogenic avian influenza H5N1 completely abolished the antiviral responses and led to high viral replication. Despite this strong antiviral inhibition by H3N2 and H5N1, I also found that pBECs released low levels of a key antiviral protein called interferon (IFN) - beta even without viral infection. This constitutive IFN-beta release was further shown to counter-act the suppressive effect by the NS1 protein in an attempt to limit viral replication. 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.

This work also forms the basis of my current project that examines the underlying reasons for the increased susceptibility and more severe complications following influenza infection in people with chronic airways diseases such as asthma and chronic obstructive pulmonary disease (COPD). By using pBECs from healthy, asthmatic and COPD subjects, we are exploring the innate immune signalling and responses to influenza viruses and rhinoviruses using whole genome microarray and other molecular biological techniques. We are also investigating the pathogenesis of influenza viruses, including seasonal influenza H3N2, swine-origin H1N1/09 that caused 2009 influenza pandemic and recently isolated oseltamivir-resistant H1N1/09, low pathogenic avian influenza H11N9, and highly pathogenic avian influenza H5N1 in collaboration with World Health Organization. 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 respiratory infectious diseases.

Qualifications

• PhD (Medicine), University of Newcastle, 2010

Research

Research keywords

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

Research expertise

Molecular biology, virology, and immunology

Collaboration

I am currently collaborating with Prof. Philip Hansbro's group in establishing the mechanisms of high susceptibility of COPD to influenza infection in a mouse model of COPD, and with Prof. Peter Gibson and Dr. Katherine Baines in the investigation of abnormal immune signalling in COPD pBECs using whole genome microarray analysis.

I am collaborating with Prof. Takashi Fujita at the Institute of Virus Research Kyoto University in elucidating the mechanisms of antiviral interferon responses during viral infection.

We are also collaborating with World Health Organisation (WHO) Collaborating Centre for Reference and Research on Influenza in influenza research, and CSIRO - Australian Animal Health Laboratory.

Languages

• Chinese
• English

Fields of Research

Centres and Groups

Centre

• PRC - Priority Research Centre for Asthma & Respiratory Diseases

Group

Memberships

Other

• Member - Australasian Society for Immunology
• Member - International Society for Interferon and Cytokine Research
• Member - The Thoracic Society of Australia & New Zealand

Awards

Other

2012	TSANZ Travel Award Thoracic Society of Australia and New Zealand (Australia) Travel award for TSANZ at Canberra, ACT, Australia
2009	TSANZ Travel Award Thoracic Society of Australia and New Zealand (Australia) Travel award for TSANZ at Darwin, NT, Australia

Research Award.

2012	Winner - Ann Woolcock Young Investigator Award Thoracic Society of Australia and New Zealand (Australia) The Winner of Ann Woolcock Young Investigator Award, the most prestigious award in the area of research made by the premier respiratory society of Australia and New Zealand

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Teaching

Teaching expertise

Honour projects and RHD projects are available