RESEARCH (What we do)
The primary goal of my lab is to elucidate the molecular events underlying Parkinson’s and related neurodegenerative diseases, with the view to develop novel diagnostics and therapies aimed at effectively managing these debilitating disorders. To realize this goal, our research work focuses on achieving the following inter-related objectives targeting at the entire disease continuum.
DETECTION – To detect the disease earlier and identify at-risk individuals
PROTECTION – To offer neuroprotective strategies for patients in early disease stages
RESTORATION - To offer cell replacement therapy for patients in advanced disease stages
We adopt a multi-pronged approach, including the use of different disease models such as Drosophila, mouse and patient-derived human neurons and brain organoids, as well as marmosets (work in progress) to achieve our objectives.
DROSOPHILA WORK
Drosophila melanogaster is a simple yet versatile animal model to approach outstanding questions regarding Parkinson's disease. Our laboratory utilises genetically modified flies that express genes implicated in the pathogenesis of Parkinson's disease. Using the UAS-Gal4 system, flies can be crossed to drive cell and tissue-specific genetic expression in its progeny. Thereafter, drug treatments are carried out in these flies to help us identify drugs with neuroprotective potential.
CELL CULTURE
Aberration in the ubiquitin-proteosome system and mitochondrial quality control has been implicated in the pathogenesis of Parkinson's disease. Faulty mitochondria are removed via a tightly regulated autophagy process known as mitophagy. In cell culture, we are able to study the physiological role of proteins involved in mitophagy and employ various imaging, genetic and molecular approaches to explore and verify our experiments.
REGENERATIVE MEDICINE
The advent of the induced pluripotent stem cell (iPSC) technology in a new era looks set to revolutionize not only regenerative medicine, but also the way we study disease pathogenesis. In 2015, our lab reported the successful generation of dopaminergic neurons from cord lining-derived induced pluripotent stem cells (CLiPS). Implantation of reprogrammed dopaminergic neurons in Parkinson's disease mouse models alleviated the phenotypic characteristics of Parkinson's disease effectively. We are currently in collaboration with CellResearch Corporation and Professor Balazs Gulyas from LKC School of Medicine, NTU, towards translation for human therapy.