In a nutshell, tell us about your research
At the Chan Lab, we study metabolism – the process that breaks down chemical substances like nutrients in the food we eat to provide energy. The brain, being such a complex organ, requires a lot of energy. We want to know at the fundamental level, what provides brains with the energy they need to function and how changes in brain metabolism can lead to various neurological conditions, including epilepsy.
A focus of the lab is rare genetic epilepsies such as tuberous sclerosis complex (TSC) and mitochondrial disease. Through years of research, we have found that these genetic epilepsies often have a strong metabolic component. Amino acids, the building block of proteins, are particularly important for brain energy. However, we want to understand more about which specific amino acids are significant in epilepsy and whether we can supplement or reduce the amount of them to provide the brain with a healthy level of energy. Interestingly, too much or too little energy supplied to the brain can lead to epilepsy – so it’s a delicate balancing act to get that right level for healthy brain function.
What impact do you hope your research will have?
We hope that our research can lead to new treatments for epilepsy. You may have heard about the ketogenic diet – a low-carbohydrate, high fat diet that is effective in treating some forms of epilepsy. The ketogenic diet is a successful example of how targeting brain metabolism by supplying the right level of brain energy, can treat epilepsy. Despite the success we have had with ketogenic diet, there have been no new treatments for epilepsy that target brain metabolism and we want to change that.
We know that a high level of the amino acid, lysine, is broken down in the brains of patients with tuberous sclerosis complex. We think that this breakdown results in the production of a toxic brain compound that causes epilepsy, so we are working with clinical colleagues to develop a dietary treatment which limits the amount of lysine consumed. If successful, this new diet could be tested for patients with tuberous sclerosis complex and perhaps, in the future, epilepsy. We are also working with Professor Wyatt Yue, at Newcastle University, in our current Epilepsy Research Institute-funded project to design a new drug molecule that would block lysine breakdown in the brain. Alongside this, we are exploring whether a gene therapy approach can also be used to target brain metabolism to treat epilepsy.
Overall, we want our research to one day result in meaningful change and new treatments for the many patients still living with drug-resistant epilepsy.
What have you recently been working on as part of the Neurodevelopment research theme?
It has been a great honor to have been selected as one of the Theme Leads for the Neurodevelopment research theme at the Epilepsy Research Institute. Together with my co-theme leads, Professor Sameer Zuberi (Glasgow) and Professor Juan Burrone (King’s College London), we are assembling a Neurodevelopment task force to tackle the big challenges of neurodevelopment and epilepsy. We are pleased to see commitments from UK and international leaders in the field to support our work.
We aim to first define the landscape of neurodevelopment and epilepsy research to identify the challenges, barriers, and obstacles we face in the field. Then, we want to systematically address these challenges to enable and facilitate ground-breaking research into neurodevelopment. To do this, we hope to recruit an intern, who will help us to kickstart some of the project ideas we have and work with the larger Neurodevelopment Task Force to get the ball rolling. I would encourage everyone to make sure they are signed up to The Hub to stay tuned on our progress!
What do you hope the Neurodevelopment theme will achieve for people affected by epilepsy?
I believe the biggest challenge for the Neurodevelopment theme is the gaps in our current understanding of how the brain develops. These knowledge gaps include how disruption in this development process can lead to epilepsy. We are now at a stage where we are identifying more and more genes associated with childhood epilepsy. However, as we identify new genes, we are not understanding or defining how these genes lead to epilepsy. Furthermore, some of these genetic mutations can be ‘ultra-rare’, with some only having been identified in 10-20 people worldwide so far. Additionally, we now also know that changes in the gene structure can also cause epilepsy, so this is a complex area of research.
We really hope that through the Neurodevelopment Theme, we can collaborate and work together to start addressing some of these gaps in our knowledge. If we can come together as a team within the UK and also globally, we can hopefully make some meaningful impact in this field.
What are your hopes for the future of epilepsy research?
I have high hopes for the future of epilepsy research. I think we are at a critical turning point as the UK landscape is dynamically changing and we are seeing many new emerging leaders in the field with fresh ideas and approaches to the challenges we face. We are also seeing many researchers from related fields such as autism or other neurodevelopmental conditions, joining the epilepsy field through collaborations. It really is an exciting time to be involved in epilepsy research!
Finally, I want to finish by saying how inspired I continue to be by people affected by epilepsy, and their positive outlook and enthusiasm to get involved in research. The involvement of people with epilepsy, their families, caregivers, and those bereaved by epilepsy is essential to ensure that our research aligns with the reality of living with epilepsy. I have certainly benefited from interactions with the Epilepsy Research Institute’s Shape Network and hope to continue engaging with the network in my research. Sometimes, the best ideas can come from the conversations we have when we step away from the lab bench for a while and are reminded of why research into epilepsy is needed.
