I live with three lovely cats and my dear wife. I love to sing while I am driving.

I started off my postdoctoral training in studying oligodendrocytes in sporadic Alzheimer's disease. Oligodendrocyte is the only cell type to make myelination in the central nervous system, and I am specialised in studying the cell biology underlying myelin degradation in the ageing brain. We hypothesised that the oligodendrocytes are highly vulnerable to the DNA damage accumulated during the ageing process. With the success of disease modifying therapies (DMTs), MS patients are expected to live a full lifespan, and the MS population is now ageing. I am inspired to provide a better understanding of age-related changes in oligodendrocytes in the multiple sclerosis (MS) population, and hopefully we can find a way to slow down or even prevent the transition into the progressive state.

There are three exciting developments for MS research recently. First, it is the identification of Epstein-Barr virus (EBV) infection as a strong risk factor for MS. Second, it is the advancement of chemical exchange saturation transfer (CEST) technique in magnetic resonance imaging (MRI), which is an important tool for monitoring brain-specific molecular and metabolic changes for the patients. Finally, the recognition of myelination as an activity-dependent process mediated by the oligodendrocytes is likely to make a difference in the remyelination strategies for the future.

In this project, we hypothesise that the build-up of tau, a small structural protein in brain cells, is caused by excessive demyelination in progressive MS. In particular, we proposed that the myelinating cells, oligodendrocytes, play a role in regulating tau protein transport by expressing a cell-type specific adaptor molecule, BIN1 (Bridging integrator 1). When oligodendrocytes are compromised during demyelination, such BIN1-mediated tau regulation becomes dysfunctional and leads to tauopathy in progressive MS. By using a high-throughput digital pathology approach, we will look into the archival tissue slides in the MS Australia Brain Bank and unlock the valuable information towards these hypotheses. By cross examining these observations in cell culture and in vivo models, we would like to address whether oligodendrocyte-specific BIN1 function is associated with tauopathy at the early stage of RRMS-to-SPMS transition.

For individuals with MS, the shift from relapsing-remitting MS (RRMS) to secondary progressive MS (SPMS) represents a crucial stage that is linked to increased disability. While DMTs have successfully enhanced care and extended the lives of RRMS patients, it also contributed to a notable shift in MS epidemiology, resulting in an ageing MS population. With older age and longer disease duration the two major risk factors for SPMS transition, the increased longevity will come with a growing number of patients entering this progressive disease phase. By clarifying whether tau protein is accumulating early on during SPMS transition, and if such aggregation is associated with BIN1 loss in the oligodendrocyte lineage, this project will address the underlying cellular mechanism and provide insights of whether tau could be an early biomarker of SPMS transition.

As a basic scientist, the most enjoyable thing about working in the lab is having your novel hypothesis tested with the latest technologies and talents across different walks of professions. The excitement is no less than exploring an uncharted deep space as the Captain of the Starship Enterprise. As a researcher working on MS and other neurodegenerative diseases, this excitement comes with great responsibility because our exploration may eventually be able to help the patients and their families one day. These excitements and responsibilities come with many difficulties. Funding, staffing and having our discovery translate into meaningful outcomes for the patients are all part of the challenges. By inspiring more young minds into scientific research and advocating the public on the importance of our work are pivotal for us to make a difference.