Research Interests :
Neurogenesis, which persists in the adult mammalian brain, may provide a basis for neuronal replacement therapy in neurodegenerative disease (NDD), like Alzheimer disease (AD). Despite intense investigations, no effective therapy is currently available to prevent the onset or to halt the progression of the neuronal cell loss. Therefore, in recent years research has mainly been focused on the mechanisms of endogenous repair processes occurring in the adult brain. Our research interest however is to unravel the molecular basis of neurogenesis underlying the pathogenesis of the AD, particularly for microRNAs (miRNAs). miRNAs are the single-strand non-coding RNA that target 3'UTR of mRNAs for transcriptional repression or/and translational degradation. It has emerged as a powerful therapeutic tool for gene regulation due to its size, abundance, tissue specificity, and relative stability in plasma. Dysfunctional miRNA-mediated regulation has been associated with the pathogenesis of AD. Our ultimate goal is to identify miRNA and its target gene in mediating neurogenesis, and to help understand the basis for impaired neurogenesis that may contribute to the cognitive dysfunction observed in the diseased brain. The precise understanding of APP-miRNA-mRNA target relationships will be an absolute requirement for therapeutic effectiveness of the miRNA, and they might serve as the future therapeutic targets for the treatment of NDD.
More recently, we have been collaborating with Dr. Eng King Tan, a Clinician Scientist at the Department of Neurology, NNI, to incorporate genetically modified mice model of PD and CNS stem cell cultures into our analysis to identify any potential pathogenic factors, substrates, miRNAs and their regulatory pathways at the molecular, cellular, network, and behavioral level. Mouse models are also being used to develop and evaluate novel treatment strategies. Their relevance is assessed through the comparative studies of humans and postmortem tissues to establish prospective collaboration with clinical programs.