ZENG Li, Ph.D.
Principal Investigator, Research, National Neuroscience Institute (NNI)Associate Professor, Neuroscience and Behavioral Disorders Programme, Duke-NUS Medical SchoolAdjunct Associate Professor, Lee Kong Chian School of Medicine, Nanyang Technological University
Neural Stem Cell Research Laboratory
Research DepartmentNational Neuroscience Institute11 Jalan Tan Tock Seng, Singapore 308433 Tel: (65) 6357 7515 (Office) / (65) 6357 7505 (Lab) Email: Li_ZENG@nni.com.sg
Image taken 2019
Alzheimer’s disease (AD) is the most common neurodegenerative disease seen in Singapore. Recent evidences suggested that impaired neurogenesis might contribute to cognitive dysfunction observed in AD. Amyloid precursor protein (APP) is a type I transmembrane glycoprotein proteolytically processed to release Aβ (amyloid beta), a pathological hallmark of AD. Although, this protein is expressed throughout the developing and mature brain; the roles of APP in neural development and neural stem cell function are not well established. microRNAs (miRNAs) are small non-coding RNA molecules that function in the transcriptional and post-transcriptional regulation of gene expression in a variety of organisms.
The role of miRNAs in neuronal development and neural stem cell function has been recently identified. Notably, dysregulated miRNAs have been implicated in AD. We aim to unravel the molecular mechanisms underlying APP-dependent miRNA-mediated neuronal differentiation in AD; working with clinician doctors at NNI, we aim to develop miRNAs as biomarkers for AD by detecting miRNAs level changes in cerebrospinal fluid (CSF), and peripheral blood mononuclear cells (PBMCs) from AD subjects, compared to the healthy individuals. Our research will advance the understanding of miRNA regulatory pathway in association with impaired neurogenesis and cognitive dysfunction observed in AD. Importantly, our study will identify miRNAs as novel non-invasive diagnostic biomarkers, and help in developing miRNA-based therapeutics strategy in AD.
In addition, we have been collaborating with Professor Tan Eng King, Director of Research at NNI and a Clinician Scientist at the Department of Neurology, NNI@SGH Campus, to incorporate genetically modified mice model of PD and neural stem cell/neuron cell cultures into our analysis to identify 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 programmes.
Recently, in order to circumvent the caveat in recapitulating the complexity and delicacy of the human brain, we generate 3-dimensional model of the human brain through cerebral organoids using human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs). Our goal is to
Our study would value-add to the development of drug screening applications and personalised medicine strategy that targets dementia patients in early phase diagnosis.
iPSC-derived human dopaminergic neurons stained with TH (red) and neuronal marker Tuj1 (green) at day 36 after neuronal differentiation.
Cerebral organoid at day 120 co-stained with astrocyte marker, GFAP (green), neuronal marker, NeuN (red) and nuclear marker, DAPI.
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