The Meyer Lab, led by Jason Meyer, PhD, focuses on mechanisms of neural development and neurodegeneration using human pluripotent stem cell-derived neurons. Fundamentally, the research emphasizes the in vitro three dimensional organization and differentiation of these stem cells into organoids which serve as a model of the temporal and spatial organization of neural tissue. From these organoids, different individual cell types are isolated and utilized for studies of neurodegeneration.
Meyer Lab
Research Updates
Genetic determinants of neurodegenerative diseases are created through either the derivation of stem cells directly from patient samples, or through the introduction of the mutation with gene editing approaches. Once harboring these mutations and differentiated into the affected cell types, these cells serve as a powerful in vitro model of neurodegenerative mechanisms in a human cell model.
Currently, major emphases in the lab focus upon both the intrinsic mechanisms of disease leading to the loss of neurons, as well as those extrinsic mechanisms resulting from adversely affected interactions between neurons and glia.
Current Research Funding
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Targeting the diversity of retinal ganglion cells for replacement therapy
NIH/NEI 1R21EY031120-01 , Meyer (PI), 08/01/19–07/31/21
The overall goal of this project is to test the ability of stem cell-derived retinal ganglion cells to integrate into and repair the retina of a macaque model of glaucoma.
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Complement pathway-mediated neurotoxicity of reactive astrocytes in a stem cell model of glaucoma
Glaucoma Research Foundation, Shaffer Grant, Meyer (PI), Fortune (Co-PI), 8/03/01/21–02/28/22
The overall goal of this project is to facilitate the development of novel therapeutic approaches to glaucomatous phenotypes characterized by the presence of A1 astrocytes.
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Astrocyte modulation of retinal ganglion cells in a stem cell model of glaucomatous neurodegeneration
Brightfocus Foundation, Meyer (PI), 09/01/20–08/31/22
The overall goal of this project is to (1) assay for glaucomatous phenotype in OPTN patient-derived retinal ganglion cells; and (2) examine the role of retinal astrocytes in the progression of a glaucomatous phenotype.
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Deciphering the role of CX3CR1 in Modulating Mechanisms of Amyloid driven Neurodegeneration in Alzheimer’s Disease
NIH 1RF1AG069425-01, Lamb (PI), Meyer (Co-PI), 09/15/20–08/31/25
The overall goal of this project is to test the unique hypothesis that downregulation/loss of CX3CR1 signaling alters microglial activation and results in impaired clearance and/or increased accumulation of neurotoxic soluble Aβ oligomers. Enrichment of toxic Aβ in the micro-environment triggers a cascade of neurodegenerative signaling including the generation and spread of neurotoxic species of pTau.
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National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)
NIA/NIH, U24AG021886, Foroud (PI), Meyer (Co-I), 07/15/2002–05/31/2021
Cell repository to collect and maintain information and biological specimens on individuals with Alzheimer’s disease and other dementias.
Recent Publications
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2020
VanderWall KB, Lu B, Alfaro JS, Allsop AR, Carr AS, Wang S, and Meyer JS (2020), Differential susceptibility of retinal ganglion cell subtypes in acute and chronic models of injury and disease, Sci Reports, 10(1): 17359.
Fligor CM, Huang KC, Lavekar SS, VanderWall KB, and Meyer JS (2020), Differentiation of Retinal Organoids from Human Pluripotent Stem Cells, Methods Cell Biol, 159:279-302.
VanderWall KB, Huang KC, Pan Y, Lavekar SS, Fligor CM, Allsop AR, Lentsch KA, Dang P, Zhang C, Tseng HC, Cummins TR, and Meyer JS (2020), Retinal Ganglion Cells with a Glaucoma OPTN(E50K) Mutation Exhibit Neurodegenerative Phenotypes when Derived from Three-Dimensional Retinal Organoids, Stem Cell Reports, 15(1):52-66.
Artero-Castro A, Rodriguez-Jimenez FJ, Jendelova P, VanderWall KB, Meyer JS, and Erceg S (2020), Glaucoma as a Neurodegenerative Disease Caused by Intrinsic Vulnerability Factors, Prog Neurobiol, 193:101817.
Wang Q, Zhuang P, Huang H, Li L, Liu L, Webber HC, Dalal R, Siew L, Fligor CM, Chang KC, Nahmou M, Kreymerman A, Sun Y, Meyer JS, Goldberg JL, and Hu Y (2020), Mouse g-Synuclein Promoter-Mediated Gene Expression and Editing in Mammalian Retinal Ganglion Cells, J Neurosci, 40(20):3896-3914.
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2019
VanderWall KB, Vij R, Ohlemacher SK, Sridhar A, Fligor CM, Feder EM, Edler MC, Baucum AJ, Cummins TR, Meyer JS (2019), Astrocytes Regulate the Development and Maturation of Retinal Ganglion Cells Derived from Human Pluripotent Stem Cells, Stem Cell Reports, 12(2), 201-212. PMID 30639213.
Ohlemacher SK, Langer KB, Fligor CM, Feder EM, Edler MC, and Meyer JS (2019), Advances in the Differentiation of Retinal Ganglion Cells from Human Pluripotent Stem Cells, Adv Exp Med Biol, 1186:121-140.
Hamilton J, Brustovetsky T, Sridhar A, Pan Y, Cummins TR, Meyer JS, and Brustovetsky N (2019), Energy Metabolism and Mitochondrial Superoxide Anion Production in Pre-Symptomatic Striatal Neurons Derived from Human Induced Pluripotent Stem Cells Expressing Mutant Huntingtin, Molecular Neurobiology 57(2): 668-684.
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2018Langer KB, Ohlemacher SK, Phillips MJ, Fligor CM, Jiang P, Gamm DM, Meyer JS (2018) Retinal Ganglion Cell Diversity and Subtype Specification from Human Pluripotent Stem Cells, Stem Cell Reports 10(4), 1282-1293. PMID 29576537.
Fligor CM, Langer KB, Sridhar A, Ren Y, Shields PK, Edler MC, Ohlemacher SK, Sluch VM, Zack DJ, Zhang C, Suter DM, Meyer JS (2018) Three-Dimensional Retinal Organoids Facilitate the Investigation of Retinal Ganglion Cell Development, Organization, and Neurite Outgrowth from Human Pluripotent Stem Cells, Scientific Reports, 8(1), 14520. PMID 30266927.
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2016Ohlemacher SK, Sridhar A, Xiao Y, Hochstetler AE, Sarfarazi M, Cummins TR, and Meyer JS (2016) Stepwise Differentiation of Retinal Ganglion Cells from Human Pluripotent Stem Cells Enables Analysis of Glaucomatous Neurodegeneration. Stem Cells 34(6), 1553-62.
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2011Meyer JS, Howden SE, Wallace KA, Verhoeven AD, Wright LS, Capowski EE, Pinilla I, Martin JM, Tian S, Stewart R, Pattnaik B, Thomson JA, and Gamm DM (2011), Optic Vesicle-Like Structures Derived from Human Pluripotent Stem Cells Facilitate a Customized Approach to Retinal Disease Treatment. Stem Cells 29(8), 1206-18. PMID 21678528.
Research Team
Catia Gomes, PhD
Postdoctoral Research Associate
Kirstin VanderWall
PhD Student
Clarisse Fligor
PhD Student
Sailee Lavekar
PhD Student
Kang-Chieh Huang
PhD Student