Research

Alan Hsu’s search for a better understanding of the immune system


Alan Hsu

Dr. Alan Hsu is a post-doctoral research fellow at University of Newcastle and Hunter Medical Research Institute (HMRI). His research is focused on influenza virus infections and human immunity, and in chronic airways diseases such as asthma and chronic obstructive pulmonary disease.

What’s the issue your research is trying to solve?

Human immunology has always been the centre of most if not all diseases in us Homo Sapiens, and understanding how human immune system works has been the foundation of all my research areas. These include how our immune system fights against infectious diseases such as influenza viruses and to identify novel therapeutic targets against these viruses. With the constant mutations and emergence of new or re-emerging viruses, and with drug-resistance on the rise, this area of research is extremely important.

Another area of my research focus is to understand why people with chronic airways diseases are more susceptible to virus infections with elevated mortality. Current therapies have limited effects and the lack of knowledge of disease mechanisms has resulted in little progress toward rational therapeutic intervention. The prevalence of chronic airways diseases is increasing, research and development of novel therapeutic targets is urgently needed.

What have you discovered so far?

We have discovered that an important antiviral protein called interferon-beta (IFN-b), instead of being produced only after influenza virus infections in the airway epithelial cells (AECs), is constantly been produced at low levels by AECs at normal state, so the cells can initiate immune response immediately upon viral invasion.

Despite the importance of IFN-b and antiviral responses against virus infections, human influenza viruses produce a protein known as the non-structural (NS) 1, that effectively suppresses human antiviral immunity and promotes virus replication and spread.

More importantly high pathogenic avian influenza NS1 has the ability to completely abolish our antiviral responses, therefore leading to high death rate. The co-evolution of mammals and ever-mutating influenza viruses really shows that the survival of the fittest is clearly true here.

We have recently discovered mechanisms that make those with chronic obstructive pulmonary disease (COPD) highly vulnerable to influenza virus infections. People with COPD have chronically heightened airway inflammation, and influenza virus infections frequently cause acute exacerbations of their symptoms, leading to lengthened recovery with increased mortality.

The underpinning mechanisms are not well understood. We found that influenza viruses enter AECs from people with COPD more efficiently, and in combination with exaggerated inflammation and impaired antiviral immunity, this leads to increased virus replication compared with AECs from healthy subjects.

These phenomena in COPD centralises on abnormal activation of an important immune signalling protein called PI3K. Inhibition of PI3K suppresses influenza virus entry and infection, and enhanced antiviral responses in COPD. PI3K therefore is a potential therapeutic targets against influenza virus infections, and for those with COPD.

What’s been your biggest hurdle?

While we become the veteran of a scientific field and constant manuscript rejections, I believe the hurdles in my path is probably also the same as any other laboratory scientists, we never solve one problem without creating or observing ten more. Nevertheless, I truly believe that only by understanding the fundamental and complicated nature of immunology, and with constant training in advanced molecular biological technologies will then allow us to explore the frontiers in immunology and to design and develop next generations of therapeutic strategies.

Another hurdle would be funding opportunities. The problem with today’s national funding scheme is somewhat short-sighted. Instead of arguing how to cut the pie smaller and smaller, we should aim to create a bigger pie to fund research of national importance and unavoidable global diseases such as infectious diseases.

How far is your work from impacting patient care?

As a scientist in the field of infection and immunity, I am not certain when my work will have an impact to patient care, but I would like to share this quote by Nikola Tesla.

“The scientific man does not aim at immediate results. He does not expect his advanced ideas will be readily taken up. His duty is to lay the foundation for those who are to come, and point the way.”

As mentioned, unravelling the complexity of human immune system will not only benefit those with airways diseases, but will pave the wave for new treatment options for other diseases such as arthritis and cancer.

If you could discover one thing in your research, what would it be? (e.g what’s your holy grail?)

I don’t think it is going to one “thing”, but a category of things in my research that I hope to achieve and contribute to our society. Discovery of new strategies that can be used to prevent and treat infectious diseases such as influenza, ebola, and zika virus. Another area of discovery that I would like to contribute to is the understanding of the immune-pathogenesis of chronic airways diseases so that novel intervention treatments can be identified and developed.

If you could take two things to a desert island what would they be?

A mega yacht, that has everything that I need to not only survive on the island, but also go back to civilisation whenever I needed to. I am sure the second thing would be somewhere on the yacht. Is it too greedy!?…

What are the two food items you couldn’t live without?

Grass-Fed ribeye and bourbon. Oh wait, is that a food?

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