Shun Fat (Kevin) Lau, PhD
Postdoctoral FellowAbout
Research
Publications
Featured Publications
The VCAM1–ApoE pathway directs microglial chemotaxis and alleviates Alzheimer’s disease pathology
Lau S, Wu W, Wong H, Ouyang L, Qiao Y, Xu J, Lau J, Wong C, Jiang Y, Holtzman D, Fu A, Ip N. The VCAM1–ApoE pathway directs microglial chemotaxis and alleviates Alzheimer’s disease pathology. Nature Aging 2023, 3: 1219-1236. PMID: 37735240, PMCID: PMC10570140, DOI: 10.1038/s43587-023-00491-1.Peer-Reviewed Original ResearchConceptsDanger-associated molecular patternsAlzheimer's diseaseMicroglial chemotaxisAmeliorate AD pathologyDisease pathologyAlzheimer's disease pathologyAmyloid-betaFunctional screeningPlaque-associatedMicroglial clearanceAD pathologyExtrinsic signalsPhagocytic clearanceExacerbate disease pathologyMolecular patternsIL-33ChemotaxisMicroglial functionAlzheimerVCAM1Interleukin-33Higher cerebrospinal fluid levelsApoPathwayMicrogliaSingle-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer’s disease
Lau S, Cao H, Fu A, Ip N. Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer’s disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 25800-25809. PMID: 32989152, PMCID: PMC7568283, DOI: 10.1073/pnas.2008762117.Peer-Reviewed Original ResearchConceptsSingle-nucleus transcriptome analysisAngiogenic endothelial cellsAlzheimer's diseaseTranscriptome analysisEndothelial cellsCell type-specific responsesCellular targetsCell type-specific transcriptomic changesNormal controlsIncreased expression of angiogenic growth factorsType-specific responsesTherapeutic developmentAntigen presentation machineryComprehensive molecular profilingSamples of AD patientsAD brainAD pathogenesisDysregulation of endothelial cellsExpression of angiogenic growth factorsDisruption of biological processesTranscriptomic changesPrefrontal cortical samplesBiological processesCellular heterogeneityAngiogenic growth factorsAn IL1RL1 genetic variant lowers soluble ST2 levels and the risk effects of APOE‐ε4 in Alzheimer’s disease
JIANG Y, Zhou X, Wong H, Li O, Ip F, Chau V, Lau S, Wu W, Wong D, Seo H, Fu W, Lai N, Chen Y, Chen Y, Tong E, Mok V, Kwok T, Mok K, Shoai M, Lehallier B, Moran‐Losada P, O’Brien E, Porter T, Laws S, Hardy J, Wyss‐Coray T, Masters C, Fu A, Ip N, Initiative A. An IL1RL1 genetic variant lowers soluble ST2 levels and the risk effects of APOE‐ε4 in Alzheimer’s disease. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.064428.Peer-Reviewed Original ResearchGenome-wide association studiesGenetic regulationAlzheimer's diseaseGenome-wide association study analysisGenetic variantsPathogenesis of Alzheimer's diseaseAD risk genesDisease-causing roleAPOE-e4 carriersAssociation studiesGenetic variationAmyloid-betaRisk genesMicroglial clearanceBrains of patientsBackground genetic factorsAD therapySevere neurodegenerationMicroglial dysfunctionAb accumulationMicroglial functionDecoy receptorGenetic factorsAPOE-e4IL1RL1IL-33-PU.1 Transcriptome Reprogramming Drives Functional State Transition and Clearance Activity of Microglia in Alzheimer’s Disease
Lau S, Chen C, Fu W, Qu J, Cheung T, Fu A, Ip N. IL-33-PU.1 Transcriptome Reprogramming Drives Functional State Transition and Clearance Activity of Microglia in Alzheimer’s Disease. Cell Reports 2020, 31: 107530. PMID: 32320664, DOI: 10.1016/j.celrep.2020.107530.Peer-Reviewed Original ResearchConceptsTranscriptome profilingAlzheimer's diseaseTranscription factor bindingSignature genesMicroglial state transitionChromatin accessibilityFactor bindingTranscriptome reprogrammingClearance activityBeta-amyloidTranscriptomeAD pathologyMicroglial transcriptomeTranscriptional pathwaysMajor histocompatibility complex classMicroglial subpopulationsTranscriptomic signaturesEnhanced phagocytic activityMicroglial functionHistocompatibility complex classPhagocytic activityAlzheimerInterleukin (IL)-33Activation of microgliaChromatin
2023
Receptor–ligand interaction controls microglial chemotaxis and amelioration of Alzheimer's disease pathology
Lau S, Fu A, Ip N. Receptor–ligand interaction controls microglial chemotaxis and amelioration of Alzheimer's disease pathology. Journal Of Neurochemistry 2023, 166: 891-903. PMID: 37603311, DOI: 10.1111/jnc.15933.Peer-Reviewed Original ResearchConceptsDanger-associated molecular patternsMicroglial chemotaxisAD pathogenesisAlzheimer's diseaseMicroglial functionRepertoire of surface receptorsHyperphosphorylated tauAlzheimer's disease pathologyAmyloid-betaMolecular machineryMicroglial receptorsReceptor-ligand interactionsPhagocytic clearanceReceptor-ligand axisMolecular patternsSurface receptorsFunctional transitionDisease pathologyChemotaxisBrain homeostasisAberrant synaptic pruningClearance activityCritical stepsReceptorsAmyloid
2022
An IL1RL1 genetic variant lowers soluble ST2 levels and the risk effects of APOE-ε4 in female patients with Alzheimer’s disease
Jiang Y, Zhou X, Wong H, Ouyang L, Ip F, Chau V, Lau S, Wu W, Wong D, Seo H, Fu W, Lai N, Chen Y, Chen Y, Tong E, Mok V, Kwok T, Mok K, Shoai M, Lehallier B, Losada P, O’Brien E, Porter T, Laws S, Hardy J, Wyss-Coray T, Masters C, Fu A, Ip N. An IL1RL1 genetic variant lowers soluble ST2 levels and the risk effects of APOE-ε4 in female patients with Alzheimer’s disease. Nature Aging 2022, 2: 616-634. PMID: 37117777, PMCID: PMC10154240, DOI: 10.1038/s43587-022-00241-9.Peer-Reviewed Original ResearchConceptsAssociated with Alzheimer's diseaseGenetic variantsGenome-wide association analysisDisease-causing roleCRISPR-Cas9 genome editingEuropean-descent populationsAlzheimer's diseaseMouse transcriptomeDisease-causing factorsGenetic variationAmyloid-betaEnhancer elementsAssociation analysisDownregulated genesAD riskGenome editingMendelian randomization analysisLower AD riskDecoy receptorProtein levelsAPOE-e4Female individualsProteinVariantsModulation of microglial activation
2021
Rhynchophylline Administration Ameliorates Amyloid‑β Pathology and Inflammation in an Alzheimer’s Disease Transgenic Mouse Model
Fu W, Hung K, Lau S, Butt B, Yuen V, Fu G, Chan I, Ip F, Fu A, Ip N. Rhynchophylline Administration Ameliorates Amyloid‑β Pathology and Inflammation in an Alzheimer’s Disease Transgenic Mouse Model. ACS Chemical Neuroscience 2021, 12: 4249-4256. PMID: 34738783, DOI: 10.1021/acschemneuro.1c00600.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAPP/PS1 miceAD transgenic mouse modelAlzheimer's disease transgenic mouse modelTransgenic mouse modelUbiquitin-proteasome systemMolecular pathwaysAmyloid plaque burdenProteasome systemTranscriptome analysisAmyloid metabolismRegulating multiple molecular pathwaysDisease-associated pathologyMicroglial functional stateAmyloid pathologyMouse modelNeurodegenerative diseasesAPP/PS1Multiple molecular pathwaysImpaired hippocampal synaptic plasticityPathwayAlzheimerSynaptic plasticityTranscriptomeUbiquitinHigh-resolution two-photon transcranial imaging of brain using direct wavefront sensing
Chen C, Qin Z, He S, Liu S, Lau S, Wu W, Zhu D, Ip N, Qu J. High-resolution two-photon transcranial imaging of brain using direct wavefront sensing. Photonics Research 2021, 9: 1144. DOI: 10.1364/prj.420220.Peer-Reviewed Original ResearchTwo-photon microscope systemLiving brain of Alzheimer’s diseaseWavefront sensing algorithmSpatial resolutionThinned-skullImage contrastTwo-photon microscopyMicroscope systemOptical heterogeneitySkull techniqueAccurate correctionImaging depthLayer 5 pyramidal neuronsCortex of miceActive immune responseResolutionMinimally invasive toolSkull windowImaging of brainImmune responseCytokine signaling convergence regulates the microglial state transition in Alzheimer’s disease
Lau S, Fu A, Ip N. Cytokine signaling convergence regulates the microglial state transition in Alzheimer’s disease. Cellular And Molecular Life Sciences 2021, 78: 4703-4712. PMID: 33847763, PMCID: PMC8195901, DOI: 10.1007/s00018-021-03810-0.Peer-Reviewed Original ResearchConceptsMicroglial state transitionCytokine signaling pathwaysDanger-associated molecular patternsAlzheimer's diseaseSignaling pathwayPathogenesis of Alzheimer's diseaseAD therapeutic developmentTherapeutic developmentHyperphosphorylated tauBeta-amyloidGenetic analysisAD pathologyCytokine signalingMolecular basisAD progressionMolecular patternsMicroglial dysfunctionSignal convergenceMicroglial responseMicroglial functionStimulated microgliaFunctional stateActive statePathwayChronic activationMelanocortin receptor activation alleviates amyloid pathology and glial reactivity in an Alzheimer’s disease transgenic mouse model
Lau J, Tian M, Shen Y, Lau S, Fu W, Fu A, Ip N. Melanocortin receptor activation alleviates amyloid pathology and glial reactivity in an Alzheimer’s disease transgenic mouse model. Scientific Reports 2021, 11: 4359. PMID: 33623128, PMCID: PMC7902646, DOI: 10.1038/s41598-021-83932-4.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAmyloid pathologyAccumulation of amyloid betaMouse model of ADAlzheimer's disease transgenic mouse modelModel of ADAPP/PS1 mouse modelAPP/PS1 mouse model of ADAPP/PS1 transgenic miceMelanocortin receptor activationAD pathogenesisAmyloid-betaMelanocortin receptorsNeurofibrillary tanglesAmyloid plaquesTranscriptome analysisMelanocortin receptor signalingHippocampus-dependent synaptic plasticityAD progressionRegulating synaptic plasticityAPP/PS1 miceSynaptic plasticityMCR activitySubtypes of reactive astrocytesFunctional role