I have always been fascinated by the advent of stem cell technologies which allow us to manipulate cell fate and its proliferation, leading to the possibility of cellular therapies. Since 2007, the generation of induced pluripotent stem cells (iPSC) from somatic cells further expand the scope of stem cell application to include patient-specific disease modelling, drug screening etc. The world is ageing rapidly with ever-increasing life expectancies and dwindling birth rates in many developed and developing countries. This results in greater vulnerability towards age-related diseases like Alzheimer’s disease (AD), especially sporadic form of AD that comprises of the majority of patients.
The aim of my DPhil project on AD is to first recapitulate in models of human neuronal pathology the interaction between the Ab and Tau proteins that has been previously shown in mice. This will be carried out in a Tau knockout iPSC line and then extended to modelling Ab-Tau interaction in sporadic AD patients. We will compare the cellular phenotypes observed in patient-specific iPSC-derived neurons with the individual clinical data from the same patients. Specifically, we will take advantage of the NIHR-MRC Deep and Frequent Phenotype cohort where iPSCs have been generated from 20 patients who have all been extensively phenotyped in clinic. This will allow us to investigate the feasibility and reliability of disease modelling in sporadic AD patients, advancing from the current limitation where most preclinical studies have been carried out in familial AD mutation backgrounds. Overall, the capability to accurately model sporadic AD patients’ individual clinical and pathological state provides a more realistic platform for disease simulation, drug discovery and potential therapeutic intervention.
I graduated from National University of Singapore (NUS) with a major in molecular and cell biology and minor in biophysics. During my time at NUS, I explored basic stem cell biology in two different labs headed by Dr Baeg Gyeong Hun and Dr Wu Qiang working on Drosophila germline stem cell and mouse embryonic stem cell respectively. I had also travelled to King’s College London working on a biophysics project supervised by Prof Sasi Conte, before spending a few months working on human embryonic stem cell model of paediatric glioblastoma at Sloan Kettering Institute, New York City, under Prof Viviane Tabar.
After receiving PhD scholarship from Agency of Science, Technology and Research (A*STAR) in Singapore, I joined Dr Mahmoud Pouladi’s lab at Translational Lab in Genetic Medicine conducting research in iPSC models of Huntington Diseases specifically on the serine-421 phosphorylation site. Thereafter, I joined Prof Richard Wade-Martins’ lab in Oxford as a postgraduate student working on iPSC models of sporadic AD.