2024
Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains
Zhu B, Park J, Coffey S, Russo A, Hsu I, Wang J, Su C, Chang R, Lam T, Gopal P, Ginsberg S, Zhao H, Hafler D, Chandra S, Zhang L. Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains. Science Translational Medicine 2024, 16: eabo1997. PMID: 39475571, DOI: 10.1126/scitranslmed.abo1997.Peer-Reviewed Original ResearchConceptsProteomic analysisAlzheimer's diseasePrefrontal cortexBrain cell typesGenetics of PDParkinson's diseaseCell-cell interactionsChaperone expressionSingle-nucleus transcriptomesExpressed genesTranscriptional changesPostmortem human brainPostmortem brain tissueDiseased brainSynaptic proteinsSingle-cellDown-regulationBrain cell populationsBrain regionsCell typesNeurodegenerative disordersLate-stage PDParkinson's disease brainsDisease etiologyNeuronal vulnerabilityAtaxin-2 polyglutamine expansions aberrantly sequester TDP-43 ribonucleoprotein condensates disrupting mRNA transport and local translation in neurons
Wijegunawardana D, Nayak A, Vishal S, Venkatesh N, Gopal P. Ataxin-2 polyglutamine expansions aberrantly sequester TDP-43 ribonucleoprotein condensates disrupting mRNA transport and local translation in neurons. Developmental Cell 2024 PMID: 39419034, DOI: 10.1016/j.devcel.2024.09.023.Peer-Reviewed Original ResearchRNA-binding proteinsAtaxin-2PolyQ expansionTDP-43Like-SmLocal translationAmyotrophic lateral sclerosisDNA-binding proteinsTransactive response DNA-binding proteinLocalization of mRNAAssociated with increased riskRNA metabolismCytoskeletal mRNAsMRNA transportPolyglutamine expansionRNP condensatesMotor neuron axonsRegulatory functionsRibonucleoproteinMotor neuron integrityNeuronal integrityCortical neuronsLiquid-like propertiesNeuronal axonsMotilityRational Design of TDP-43 Derived α‑Helical Peptide Inhibitors: An In Silico Strategy to Prevent TDP-43 Aggregation in Neurodegenerative Disorders
Salaikumaran M, Gopal P. Rational Design of TDP-43 Derived α‑Helical Peptide Inhibitors: An In Silico Strategy to Prevent TDP-43 Aggregation in Neurodegenerative Disorders. ACS Chemical Neuroscience 2024, 15: 1096-1109. PMID: 38466778, PMCID: PMC10959110, DOI: 10.1021/acschemneuro.3c00659.Peer-Reviewed Original ResearchConceptsMolecular dynamics simulationsTDP-43 aggregationTDP-43Disordered C-terminal regionDynamics simulationsIntramolecular hydrogen bondsAmyloid-like filamentsPeptide inhibitorRNA/DNA-binding proteinC-terminal regionPathology of neurodegenerative diseasesNeurodegenerative diseasesAggregation of TDP-43Binding affinityStructure-based computational approachDesign of peptide inhibitorsRNA/DNA-bindingLow root-mean-square deviationRNA splicingMRNA transportPeptide-based therapeuticsRoot-mean-square deviationDevelopment of novel therapeuticsFree energy landscapeStructure predictionTDP-43 derived α-helical peptides: A novel strategy to prevent TDP-43 aggregation in neurodegenerative disorders
Salaikumaran M, Gopal P. TDP-43 derived α-helical peptides: A novel strategy to prevent TDP-43 aggregation in neurodegenerative disorders. Biophysical Journal 2024, 123: 169a. DOI: 10.1016/j.bpj.2023.11.1123.Peer-Reviewed Original Research
2023
Phase separation and pathologic transitions of RNP condensates in neurons: implications for amyotrophic lateral sclerosis, frontotemporal dementia and other neurodegenerative disorders
Naskar A, Nayak A, Salaikumaran M, Vishal S, Gopal P. Phase separation and pathologic transitions of RNP condensates in neurons: implications for amyotrophic lateral sclerosis, frontotemporal dementia and other neurodegenerative disorders. Frontiers In Molecular Neuroscience 2023, 16: 1242925. PMID: 37720552, PMCID: PMC10502346, DOI: 10.3389/fnmol.2023.1242925.Peer-Reviewed Original ResearchAberrant phase transitionsMRNA transportFormation of ribonucleoproteinMembrane-less organellesPathogenic protein aggregationStress granule assemblyALS/frontotemporal dementiaSynaptic functionNeurodegenerative diseasesProcessing bodiesCajal bodiesRNA processingHigher-order structureSpatiotemporal regulationStress granulesTransport granulesAmyotrophic lateral sclerosisGranule assemblyProtein aggregationBiomolecular condensatesMRNA stabilityGene expressionLocal translationPhysiological functionsRBPsEpstein-Barr virus–associated primary intracranial leiomyosarcoma in an immunocompetent patient: illustrative case
Tabor J, Lei H, Morales-Valero S, O’Brien J, Gopal P, Erson-Omay E, Fulbright R, Moliterno J. Epstein-Barr virus–associated primary intracranial leiomyosarcoma in an immunocompetent patient: illustrative case. Journal Of Neurosurgery Case Lessons 2023, 5: case22532. PMID: 36692065, PMCID: PMC10550697, DOI: 10.3171/case22532.Peer-Reviewed Original ResearchEpstein-Barr virusPrimary intracranial leiomyosarcomaHuman immunodeficiency virusImmunocompetent statusImmunocompetent patientsIntracranial leiomyosarcomaMainstay of treatmentGross total resectionLeft-sided headacheSmooth muscle tumorsLeft middle cranial fossaMagnetic resonance imagingMiddle cranial fossaDura-based massUncomplicated resectionPrompt diagnosisTotal resectionAssociated edemaImmunodeficiency virusPoor prognosisMuscle tumorsRare diagnosisRare tumorImmunocompromised individualsPatientsClinical utility of whole-genome DNA methylation profiling as a primary molecular diagnostic assay for central nervous system tumors—A prospective study and guidelines for clinical testing
Galbraith K, Vasudevaraja V, Serrano J, Shen G, Tran I, Abdallat N, Wen M, Patel S, Movahed-Ezazi M, Faustin A, Spino-Keeton M, Roberts L, Maloku E, Drexler S, Liechty B, Pisapia D, Krasnozhen-Ratush O, Rosenblum M, Shroff S, Boué D, Davidson C, Mao Q, Suchi M, North P, Hopp A, Segura A, Jarzembowski J, Parsons L, Johnson M, Mobley B, Samore W, McGuone D, Gopal P, Canoll P, Horbinski C, Fullmer J, Farooqi M, Gokden M, Wadhwani N, Richardson T, Umphlett M, Tsankova N, DeWitt J, Sen C, Placantonakis D, Pacione D, Wisoff J, Hidalgo E, Harter D, William C, Cordova C, Kurz S, Barbaro M, Orringer D, Karajannis M, Sulman E, Gardner S, Zagzag D, Tsirigos A, Allen J, Golfinos J, Snuderl M. Clinical utility of whole-genome DNA methylation profiling as a primary molecular diagnostic assay for central nervous system tumors—A prospective study and guidelines for clinical testing. Neuro-Oncology Advances 2023, 5: vdad076. PMID: 37476329, PMCID: PMC10355794, DOI: 10.1093/noajnl/vdad076.Peer-Reviewed Original ResearchCNS tumorsProspective studyHistologic diagnosisCentral nervous system tumorsDiagnostic accuracyCentral nervous system cancerPrimary CNS tumorsNervous system tumorsNervous system cancersCancer-associated deathsClinical trial designDiagnostic errorsPrimary diagnostic methodDNA methylation profilingMolecular diagnostic testsPrognostic subclassificationPediatric patientsHistologic subtypeWhole genome DNA methylation profilingDefinitive diagnosisPrognostic informationSystem tumorsSystem cancersPatient managementClinical utility
2022
Sequence Determinants of TDP-43 Ribonucleoprotein Condensate Formation and Axonal Transport in Neurons
Vishal SS, Wijegunawardana D, Salaikumaran MR, Gopal PP. Sequence Determinants of TDP-43 Ribonucleoprotein Condensate Formation and Axonal Transport in Neurons. Frontiers In Cell And Developmental Biology 2022, 10: 876893. PMID: 35646935, PMCID: PMC9133736, DOI: 10.3389/fcell.2022.876893.Peer-Reviewed Original ResearchAmyotrophic lateral sclerosisTDP-43A315TAxonal transportTDP-43 variantsMotor neuron degenerationTDP-43 mutationsNeuron degenerationLateral sclerosisTransport deficitsAnterograde transportNeuronsK mutationDisease-linked mutationsMotilityKey determinantPossible mechanismMutationsPrevious findingsRetrograde motilityTransport granulesAdaptor proteinSclerosisDeterminantsGranule transport
2021
Comprehensive Genomic Characterization of A Case of Granular Cell Tumor of the Posterior Pituitary Gland: A Case Report
Hong CS, Elsamadicy AA, Fisayo A, Inzucchi SE, Gopal PP, Vining EM, Erson-Omay EZ, Omay S. Comprehensive Genomic Characterization of A Case of Granular Cell Tumor of the Posterior Pituitary Gland: A Case Report. Frontiers In Endocrinology 2021, 12: 762095. PMID: 34925233, PMCID: PMC8671743, DOI: 10.3389/fendo.2021.762095.Peer-Reviewed Original ResearchConceptsGranular cell tumorPosterior pituitary glandCell tumorsPituitary glandComprehensive genomic characterizationWhole-exome sequencingImmune checkpoint inhibitorsPoor clinical outcomePituitary gland tumorsHistone deacetylase inhibitorsInstitutional review boardRadiographic compressionUnderwent resectionCheckpoint inhibitorsMedical therapyPituitary massClinical outcomesOptic nerveSignificant morbidityResidual diseaseCase reportCentral hypothyroidismPharmacologic agentsGland tumorsTherapeutic targeting
2020
Genetic characterization of an aggressive optic nerve pilocytic glioma
Hong CS, Fliney G, Fisayo A, An Y, Gopal PP, Omuro A, Pointdujour-Lim R, Erson-Omay EZ, Omay SB. Genetic characterization of an aggressive optic nerve pilocytic glioma. Brain Tumor Pathology 2020, 38: 59-63. PMID: 33098465, PMCID: PMC7585354, DOI: 10.1007/s10014-020-00383-x.Peer-Reviewed Original ResearchConceptsOptic nerve gliomaLeft optic nerve sheathLeft-sided visual lossSporadic adult casesOptic nerve sheathNeurofibromatosis type 1 syndromeType 1 syndromeWhole-exome sequencingEmpiric managementVisual lossFocal radiotherapyOptic nervePediatric populationNerve sheathOpen biopsyAdult casesBiopsy specimenBenign histopathologyClinical prognosticationPilocytic astrocytomaComplex tumorsActionable targetsVisual pathwayAdult populationTumor progressionRNA-binding proteins in neurological development and disease
Prashad S, Gopal PP. RNA-binding proteins in neurological development and disease. RNA Biology 2020, 18: 972-987. PMID: 32865115, PMCID: PMC8216196, DOI: 10.1080/15476286.2020.1809186.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRNA-binding proteinGene expressionDisease-linked RNA-binding proteinsHigh-throughput transcriptomic analysisRNA processing stepsAberrant RNA metabolismAberrant RNA processingRecent exciting studiesRNA processingRNA metabolismMRNA traffickingAlternative splicingMultifunctional proteinTranscriptomic analysisSplicing misregulationMRNA stabilityMolecular mechanismsProtein resultsNeuronal homeostasisNeurodevelopmental defectsNeuronal proteinsFunctional consequencesPleiotropic effectsSpatiotemporal controlProtein
2019
Expression of WIPI2B counteracts age-related decline in autophagosome biogenesis in neurons
Stavoe A, Gopal P, Gubas A, Tooze S, Holzbaur E. Expression of WIPI2B counteracts age-related decline in autophagosome biogenesis in neurons. ELife 2019, 8: e44219. PMID: 31309927, PMCID: PMC6634969, DOI: 10.7554/elife.44219.Peer-Reviewed Original ResearchConceptsAmyotrophic lateral sclerosisAged miceNovel therapeutic targetLate-onset neurodegenerative diseasesAge-associated neurodegenerationAge-related declineAged neuronsRisk factorsLateral sclerosisParkinson's diseaseTherapeutic targetLC3B-positive autophagosomesNeurodegenerative diseasesMammalian neuronsNeuronsSignificant decreaseDiseaseRate of autophagy
2017
Amyotrophic lateral sclerosis-linked mutations increase the viscosity of liquid-like TDP-43 RNP granules in neurons
Gopal PP, Nirschl JJ, Klinman E, Holzbaur EL. Amyotrophic lateral sclerosis-linked mutations increase the viscosity of liquid-like TDP-43 RNP granules in neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e2466-e2475. PMID: 28265061, PMCID: PMC5373408, DOI: 10.1073/pnas.1614462114.Peer-Reviewed Original ResearchConceptsRNA-binding proteinRNP granulesAmyotrophic lateral sclerosis-linked mutationsCritical cellular processesRapid fluorescence recoveryAmyotrophic lateral sclerosisBiophysical propertiesDistinct biophysical propertiesRibonucleoprotein granulesSubcellular contextCellular processesSpecific RNAToxic gainTAR-DNA binding protein 43Superresolution microscopyFluorescence recoveryLiquid-liquid phase separationMutant TDP-43Primary cortical neuronsLiquid-like propertiesTDP-43RNAProteinMutationsAxonal location
2014
MicroRNA-124 expression counteracts pro-survival stress responses in glioblastoma
Mucaj V, Lee S, Skuli N, Giannoukos D, Qiu B, Eisinger-Mathason T, Nakazawa M, Shay J, Gopal P, Venneti S, Lal P, Minn A, Simon M, Mathew L. MicroRNA-124 expression counteracts pro-survival stress responses in glioblastoma. Oncogene 2014, 34: 2204-2214. PMID: 24954504, PMCID: PMC4275412, DOI: 10.1038/onc.2014.168.Peer-Reviewed Original ResearchConceptsMiR-124 expressionMiR-124 levelsGlioblastoma patient samplesTumor cell survivalPatient samplesAggressive adult brain tumorCell survivalCell deathSurvival of miceAdult brain tumorsHypoxic gene signaturePoor patient outcomesIntracranial xenograft tumorsHypoxic cell deathIncreases cell deathPatient outcomesTumor ischemiaXenograft tumorsBrain tumorsGlioblastoma patientsIschemic regionTherapeutic resistanceTumor progressionCancer typesGene signature
2013
Advanced neuroimaging findings of pseudotumoral hemicerebellitis in an elderly male requiring surgical decompression.
Gupta R, Maralani P, Chawla S, Gopal P, Mohan S. Advanced neuroimaging findings of pseudotumoral hemicerebellitis in an elderly male requiring surgical decompression. Journal Of Neurosurgery 2013, 120: 522-7. PMID: 24329022, DOI: 10.3171/2013.11.jns13980.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnti-Bacterial AgentsCerebellar DiseasesC-Reactive ProteinDecompression, SurgicalHumansImage Processing, Computer-AssistedImmunohistochemistryInfluenza VaccinesLeukocytosisMagnetic Resonance ImagingMaleNeuroimagingNeurosurgical ProceduresPseudotumor CerebriTomography, X-Ray ComputedVaccinationVentriculostomyConceptsPseudotumoral hemicerebellitisSurgical decompressionBilateral cerebellar hemispheresSignificant mass effectAcute cerebellitisT2 hyperintensityCerebellar swellingPediatric populationRare presentationSurgical interventionElderly malesInflammatory processPial enhancementAdvanced neuroimagingCerebellar hemisphereNeuroimaging findingsMR perfusionHemicerebellitisMR spectroscopyMass effectCerebellitisDecompressionMagnetic resonance
2005
Suppression of laminin-5 expression leads to increased motility, tumorigenicity, and invasion
Yuen H, Ziober A, Gopal P, Nasrallah I, Falls E, Meneguzzi G, Ang H, Ziober B. Suppression of laminin-5 expression leads to increased motility, tumorigenicity, and invasion. Experimental Cell Research 2005, 309: 198-210. PMID: 15963983, DOI: 10.1016/j.yexcr.2005.05.013.Peer-Reviewed Original Research