Post-stroke immunosuppression dampens inflammatory processes but increases the risk of serious infections. Describe how your research aims to find the balance.
Inflammation is part of our body’s response to injury and it is a very important process for tissue repair. However, brain inflammation following a stroke can present with further deleterious consequences. It is an on-going hypothesis within the field that the brain sends out signals to dampen the immune system to reduce inflammation following a brain injury and save viable tissue, but an undesirable side-effect is that the reduced immune defence render patients with stroke with increased risk to infections. Our research aims to work out the signalling pathways involved in this communication between the brain and the immune system after stroke, and find new therapeutic targets that will be useful in reviving the immune defence against infections without causing additional inflammatory damage to the brain.
What have you and your team discovered in this area so far?
One of the mysteries of post-stroke immunosuppression is how the brain communicates with the immune system. During my postdoctoral training in Canada, I learned that immune cells readily respond to neurotransmitters and alter their behaviour and function. Indeed, I discovered that the release of sympathetic neurotransmitters following a stroke contributes significantly in impairing the antibacterial functions of immune cells. In addition, we have known for many years that patients with stroke are prone to infections, but we know very little about why, and where these infections come from. In 2016, I led a multidisciplinary team to reveal for the first time that stroke not only damages the brain but also weakens the immune system in such a way that the bacteria in our gut have the opportunity to travel to other organs of our body, including the lung, and cause pneumonia and other infections.
Gut barrier integrity is one piece of the puzzle. What do we need to understand?
The gut is a very interesting and complicated organ. In addition to its well-known digestive functions, the gut forms an important barrier that constantly interacts and protects us from potential foreign pathogens. This barrier is also highly innervated, dynamic and commonly known as the “second brain”. Due to all of these abovementioned properties, what we currently know about the gut is actually very little. We need to go back to the drawing board and understand some of the fundamental biology and signalling mechanisms, and identify potential new targets to better tailor treatments for patients, improve their outcomes and save lives.
What aspect of this research excites you the most?
I have always been fascinated by the complexity of our bodies and the intricate crosstalk between the biological systems. Specifically, I am intrigued by why and how an injury in the brain, such as stroke, can cause devastating infectious complications. Through my research, I am beginning to appreciate that nothing happens in isolation within our body, and unwinding this intertwining intricacy that leads to therapeutic discovery is what excites me.
How long before your work might impact patient care?
I would like to think that our work is starting to impact on patient care. I value the opportunities to communicate and discuss our experimental findings with stroke clinicians. This communication channel not only allows for open discussion of our research findings, but a fantastic pathway for us to be aware of the unmet clinical needs.
What’s your Holy Grail – the one thing you’d like to achieve in your research career?
My ultimate career goal is to make a difference in the current management of patients with stroke. It would be terrific to develop a diagnostic kit to identify patients at risk of gut-derived infection. The identification of these patients to stroke clinicians will refine patient management, improve their decision-making and potentially avoid the overuse of ineffective antibiotics. In addition, now that we discovered the gut actually has a lot to answer for in post-stroke infection, I would like to develop novel therapeutics to target and restore the gut barrier integrity as a form of alternative treatment.
Immune cells or cytokines: which do you find most fascinating?
This is a difficult question – how I see it is that immune cells are the guardians in our body defending and protecting us against harmful pathogens and dangers; whilst cytokines are a group of mediators that are vital for the immune cells to communicate and know what to do. Together, they form an effective and important defence team to detect and eliminate ‘danger’ within our bodies.
What is your biggest research hurdle?
I am a basic science researcher working on ways to improve human health. So naturally, one of the biggest hurdles I face is how to make sense of our experimental findings in the real world – that is, the dreaded word of “translation”. Despite this, I believe there is a lot of value in basic research, as clearly there are unmet clinical needs that rely on discovery through fundamental biology.
Who has inspired you in work or life?
During my postdoctoral training, I had an invaluable opportunity to speak at a charitable function attended by volunteers and family members of patients with stroke. I left the event being reminded that everything we do every day is for actual people, and I am humbled and honoured to have a job that can make a real difference in someone’s life. Also, seeing my nieces and nephew grow up is a constant reminder of how complicated and amazing the human body is.