Neural Stem Cell Research Laboratory

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hidden"> </div> <div class="clear-15"></div> <div class="section_main-content"> <div class="content"> <span class="font-size-content"><div id="ctl00_PlaceHolderMain_ctl03_label" style='display:none'>Page Content</div><div id="ctl00_PlaceHolderMain_ctl03__ControlWrapper_RichHtmlField" class="ms-rtestate-field" style="display:inline" aria-labelledby="ctl00_PlaceHolderMain_ctl03_label"><p> <strong></strong> <img src="/research-innovation/PublishingImages/NNI%20Researcher%20Zeng%20Li.jpg" alt="" style="margin:5px;width:200px;height:239px;" /> <br></p><p> <strong></strong></p><p> <strong>ZENG Li, Ph.D.</strong><br></p><p> <strong></strong> <strong>Principal Investigator,</strong> Research, National Neuroscience Institute (NNI)<br><strong>Associate Professor,</strong> Neuroscience and Behavioral Disorders Programme, Duke-NUS Medical School<br><strong>Adjunct Associate Professor,</strong> Lee Kong Chian School of Medicine, Nanyang Technological University</p><p> </p><p> <strong></strong></p><p> <strong>Contact Information</strong></p><p></p><p>Neural Stem Cell Research Laboratory<br>Research Department<br>National Neuroscience Institute<br>11 Jalan Tan Tock Seng, Singapore 308433 <br>Tel: (65) 6357 7515 (Office) / (65) 6357 7505 (Lab) <br>Email: <a href="mailto:Li_ZENG@nni.com.sg" target="_blank"><span class="__cf_email__" data-cfemail="367a5f696c7378717658585f1855595b184551">[email protected]</span></a></p><p> </p><p> <strong></strong></p><p> <strong>The Team</strong></p><ul><li>TU Haitao, Ph.D. (Research Fellow)</li><li>CHI Li, Ph.D. (Visiting Research Fellow)</li><li>HANG Zhi Wei, B.Sc. (Senior Research Officer) </li><li>Sarivin VANAN, B.Sc. (Ph.D. student)</li><li>Jolene LEE Wei Ling, B.Sc. (Ph.D. student)</li><li>CHIA Sook Yoong, B.Sc. (Laboratory Manager)</li></ul><p> <img src="/research-innovation/our-laboratories/PublishingImages/NSCRL_2022.png" alt="" style="width:350px;height:262px;" /> </p><p> <strong> </strong></p><p> <strong>Overview</strong><br></p><p></p><p>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.</p><p>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.</p><p>In addition, we have been collaborating with Professor Tan Eng King, a Clinician Scientist at the Department of Neurology, NNI@SGH, 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.</p><p>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).</p><p>Our goal is to</p><ol><li>Elucidate the molecular pathology of NNI dementia patient iPSC-derived cerebral organoids</li><li>Characterise the differential spatiotemporal cellular expression of molecular markers</li><li>Identify aberrant neuronal signaling of the diseased lines in hopes to better define cellular hallmarks in early disease progression.</li></ol><p>Our study would value-add to the development of drug screening applications and personalised medicine strategy that targets dementia patients in early phase diagnosis.</p><p> <img src="/research-innovation/our-laboratories/PublishingImages/NSCRL_Neurons_2022.png" alt="" style="margin:5px;width:300px;height:301px;" /> </p><p> <span class="ms-rteFontSize-1">iPSC-derived human dopaminergic neurons stained with TH (<span class="ms-rteForeColor-2">red</span>) and neuronal marker Tuj1 (<span class="ms-rteForeColor-6">green</span>) at day 36 after neuronal differentiation.</span></p><p> <span class="ms-rteFontSize-1"> <img src="/research-innovation/our-laboratories/PublishingImages/NSCRL_Neurons_2022_B.png" alt="" style="margin:5px;width:300px;height:300px;" /></span></p><p> <span class="ms-rteFontSize-1">The image shows staining for markers of autophagy (<span class="ms-rteForeColor-6">green</span>) and dopaminergic neurons (<span class="ms-rteForeColor-2">red</span>) in brain tissue from LRRK2-mutant mice.</span></p><p> <strong> </strong></p><p> <strong>Selected Publications</strong></p><font face="Calibri" size="3"><font face="Calibri" size="3"><span lang="EN-GB"><p align="JUSTIFY" dir="LTR"></p></span></font></font><p></p><strong class="ms-rteThemeFontFace-1"><font color="#212121" size="1"><font color="#212121" size="1"><font color="#212121" size="1"><p align="JUSTIFY" dir="LTR"></p> </font></font></font></strong><font class="ms-rteThemeFontFace-1" size="3"><font size="3"><p align="JUSTIFY" dir="LTR"></p> <ol dir="ltr"><li><div align="JUSTIFY">Jiang M, Jang SE, <strong style="text-decoration:underline;">Zeng L</strong>. The Effects of Extrinsic and Intrinsic Factors on Neurogenesis. Cells　2023. doi:10.3390/cells12091285</div></li><li><div align="JUSTIFY">Long YH, Ang KS, Li M, Kelvin Chong KL, Sethi R, Zhong C, Xu H, Ong ZW, Sachaphibulkij K, Chen A, <strong style="text-decoration:underline;">Zeng L</strong>, Fu H, Wu M, Lina Lim HK, Liu L, Chen J. Spatially informed clustering, integration, and deconvolution of spatial transcriptomics with GraphST. <strong>Nature Communicatio</strong><strong>n </strong>2023. Doi: 10.1038/s41467-023-36796-3</div></li><li><div align="JUSTIFY">Kumar P, Lim A, Hazirah SN, Chua CJH, Ngoh A, Poh SL, Yeo TH, Lim J, Ling S, Sutamam NB, Petretto E, Low DCY, <strong style="text-decoration:underline;">Zeng L</strong>, Tan EK, Arkachaisri T, Yeo JG, Ginhoux F, Chan D, Albani S. Single-cell transcriptomics and surface epitope detection in human brain epileptic lesions identifies pro-inflammatory signaling. Nat Neurosci. 2022 Jul;25(7):956-966.</div></li><li><div align="JUSTIFY">Zhang ZWⴕ, Tu HTⴕ, Jiang M, Vanan S, Chia SY, Jang SE, Saw WT, Ong ZW, Ma DR, Zhou ZD, Xu J, Guo KW, Yu WP, Ling SC, Margolin RA, Chain DG, <strong style="text-decoration:underline;">Zeng L</strong>*, Tan EK*. APP Intracellular Domain Promotes Expression of LRRK2 Enabling a Feed-Forward Loop of Neurodegeneration in Parkinson’s Disease. <strong>Science Signaling </strong>2022. DOI: 10.1126/scisignal.abk3411. *co-senior authors</div></li><li><div align="JUSTIFY">Chia SYⴕ, Vipin Aⴕ, Ng KP, Tu HT, Bommakanti A, Wang BZ, Tan YJ, Zailan FZ, Ng ASL, Ling SC, Okamura K, Tan EK, Kandiah N*, <strong style="text-decoration:underline;">Zeng L</strong>*. Upregulated Blood miR-150-5p in Alzheimer’s Disease Dementia Is Associated with Cognition, Cerebrospinal Fluid Amyloid, and Cerebral Atrophy. <strong>Journal of Alzheimer’s Disease</strong> 2022. DOI: 10.3233/JAD-220116. *co-senior authors</div></li><li><div align="JUSTIFY">Tu H, Zhang ZW, Qiu L, Lin Y, Jiang M, Chia SY, Wei YF, Ng ASL, Reynolds R, Tan EK, <strong style="text-decoration:underline;">Zeng L</strong>. Increased expression of pathological markers in Parkinson’s disease dementia post-mortem brains compared to dementia with Lewy bodies.<strong> BMC neuroscience </strong>2022. DOI:10.1186/s12868-021-00687-4</div></li><li><div align="JUSTIFY">Jang SEⴕ, Qiu Lⴕ, Cai X, Lee JWL, Zhang W, Tan EK, Liu Bin, <strong style="text-decoration:underline;">Zeng L</strong>. Aggregation-induced Emission (AIE) Nanoparticles Labeled Human Embryonic Stem Cells (hESCs)-derived Neurons for Transplantation. <strong>Biomaterials</strong> 2021. DOI:10.1016/j.actbio.2018.07.051</div></li><li><div align="JUSTIFY">Jiang M, Tu HT, Zhang K, Zhang W, Yu WP, Xu J, Tan EK, Guo KH, <strong style="text-decoration:underline;">Zeng L</strong>. Impaired neurogenesis in the hippocampus of an adult VPS35 mutant mouse model of Parkinson’s disease through interaction with APP. <strong>Neurobiology of Disease </strong>2021. DOI: 10.1016/j.nbd.2021.105313</div></li><li><div align="JUSTIFY">Jiang M, Vanan S, Tu HT, Zhang W, Zhang ZW, Chia SY, Jang SE, Zeng XX, Yu WP, Xu J, Guo KH, <strong style="text-decoration:underline;">Zeng L</strong>. APP Intracellular Domain (AICD)-dependent regulation of FOXO3a Inhibits Adult Hippocampal Neurogenesis, <strong>Neurobiology of Aging</strong> 2020. DOI: 10.1016/j.neurobiolaging.2020.07.031.</div></li><li><div align="JUSTIFY">Damodar VR Qiu L, Lee JWL, Chen X, Jang SE, Chai C, Lim, KL, Tan EK, Zhang Y, Huang WM, <strong style="text-decoration:underline;">Zeng L</strong>. A microfiber scaffold-based 3D in vitro human neuronal culture model of Alzheimer’s disease. <strong>Biomaterials Science</strong> 2020. DOI: 10.1039/d0bm00833h.</div></li><li><div align="JUSTIFY">Qiu L., Liao M.C. et al., <span style="text-decoration:underline;"><strong>Zeng L</strong></span><strong style="text-decoration:underline;">.</strong>* & Robins E.G.*. Dopamine transporter neuroimaging accurately assesses the maturation of dopamine neurons in a preclinical model of Parkinson’s disease. <strong>Stem Cell Research & Therapy </strong>2020. DOI: 10.1186/s13287-020-01868-4. *co-senior authors</div></li><li><div align="JUSTIFY">Vanan S., Zeng X., Chia S.Y., Varnäs K., Zhang K., Jiang M., Padmanabhan P., Yu W.P., Zhou Z.D., Halldin C., Gulyás B., Tan E.K., <strong style="text-decoration:underline;">Zeng L</strong>. Altered striatal dopamine levels in Parkinson’s disease VPS35 D620N mutant transgenic aged mice. <strong>Molecular Brain </strong>2020. DOI: 10.1186/s13041-020-00704-3</div></li><li><div align="JUSTIFY">Jang SE, Qiu L, Chan LL, Tan EK and <strong style="text-decoration:underline;">Zeng L</strong>. Current status of stem cell-derived therapies for Parkinson’s disease: From Cell Assessment and Imaging Modalities to Clinical Trials. <strong>Frontiers in Neuroscience</strong> 2020. 14, 5585324. DOI: 10.3389/fnins.2020.558532</div></li><li><div align="JUSTIFY">Zhang W,　Tan YW,　Yam WK,　Tu H,　Qiu L,　Tan EK,　Chu JJH,　<strong style="text-decoration:underline;">Zeng L</strong>. In utero infection of Zika virus leads to abnormal central nervous system development in mice. <strong>Sci Rep</strong>.　2019. 13;9(1):7298. DOI: 10.1038/s41598-019-43303-6.</div></li><li><div align="JUSTIFY">Chen Z, Zhang W, Chua LL, Chai C, Li R, Lin L, Cao Z, Angeles D. C, Stanton W. L, Peng J, Zhou ZD, Lim KL, <strong style="text-decoration:underline;">Zeng L</strong>.* Tan EK*. Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson’s disease. <strong>Sci Signal</strong>. 2017. 10(488). pii: eaam6790. DOI: 10.1126/scisignal.aam6790. *co-senior authors.</div></li><li><div align="JUSTIFY">Qiu L, Liao MC, Chen AK, Wei S, Xie S, Reuveny S, Zhou ZD, Hunziker W, Tan EK, Oh SKW, <strong style="text-decoration:underline;">Zeng L</strong>. Immature Midbrain Dopaminergic Neurons Derived from Floor-Plate Method Improve Cell Transplantation Therapy Efficacy for Parkinson's Disease. <strong>Stem Cells Transl Med</strong>. 2017. DOI: 10.1002/sctm.16-0470.</div></li><li><div align="JUSTIFY">Chen Z, Cao Z, Zhang W, Gu M, Zhou ZD, Li B, Li J, Tan EK*, <strong style="text-decoration:underline;">Zeng L</strong>.* LRRK2 Interacts with ATM and Regulates Mdm2-p53 Cell Proliferation Axis in Response to Genotoxic Stress. <strong>Hum Mol Genet </strong>2017. 26(22):4494-4505. DOI: 10.1093/hmg/ddx337. *co-senior authors</div></li><li><div align="JUSTIFY">Zhang W, Kim PJ, Chen Z, Lokman H, Qiu L, Zhang K, Rozen SG, Tan EK, Je HS, <strong style="text-decoration:underline;">Zeng L</strong>. MicroRNA-128 Regulates the Proliferation and Neurogenesis of Neural Precursors by Targeting Pericentriolar Material 1 (PCM1) in the Developing Neocortex. <strong>eLlife</strong> 2016. 5. pii: e11324. DOI: 10.7554/eLife.11324.</div></li><li><div align="JUSTIFY">Qiu, L., Ng, G., Tan, E.K., Liao, P., Kandiah, N., <strong style="text-decoration:underline;">Zeng, L</strong> (2016) Chronic cerebral hypoperfusion enhances Tau hyperphosphorylation and reduces autophagy in Alzheimer’s disease mice. <strong>Sci Rep</strong>. 6:23964. DOI: 10.1038/srep23964.</div></li><li><div align="JUSTIFY">Zhang, W., Thevapriya, S., Kim, P.J., Yu, W., Je, HS., Tan, E.K., <strong style="text-decoration:underline;">Zeng, L</strong> (2014) Amyloid precursor protein regulates neurogenesis by antagonizing miR-574-5p in the developing cerebral cortex. <strong>Nat. Commun</strong>. 5:3330. 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