Michael Stankewich, PhD
Associate Research Scientist in PathologyDownloadHi-Res Photo
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Associate Research Scientist in Pathology
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Pathology
Associate Research ScientistPrimary
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Education & Training
- PhD
- University of Massachusetts (1997)
Research
Overview
A major player of the neuronal cortical cytoskeleton is spectrin, a large and abundant scaffolding protein. The spectrin gene family is comprised of seven genes encoding two alpha and five beta subunits. To add to the complexity, many pre-mRNA splice variants have been identified. The ascribed function for spectrin is stabilizing membranes and organizing protein and lipid micro domains on both the plasma membrane and intracellular organelles. Not only is spectrin important in maintaining membrane micro domains, but also is likely involved in their targeting and transport. Salient characteristics of the spectrin gene family include: 1) a diverse neuronal compartmentalization, 2) Ca2+ /calmodulin mediated regulation, 3) calpain/caspase mediated proteolysis, and 4) tyrosine phosphorylation and ubiquination. My interest is to better elucidate the roles for such sub cellular compartmentalization and posttranslational modifications of the spectrin cytoskeleton and how spectrin affects receptor targeting, trafficking (exocytosis and endocytosis) and stabilization at pre/postsynaptic membranes.
Research at a Glance
Yale Co-Authors
Frequent collaborators of Michael Stankewich's published research.
Publications Timeline
A big-picture view of Michael Stankewich's research output by year.
Jon Morrow, PhD, MD
Michael Kashgarian, MD, FASN
Paul Stabach
Thomas Ardito, BS
13Publications
1,300Citations
Publications
2024
The loss of βΙ spectrin alters synaptic size and composition in the ja/ja mouse
Stankewich M, Peters L, Morrow J. The loss of βΙ spectrin alters synaptic size and composition in the ja/ja mouse. Frontiers In Neuroscience 2024, 18: 1415115. PMID: 39165342, PMCID: PMC11333264, DOI: 10.3389/fnins.2024.1415115.Peer-Reviewed Original ResearchConceptsJa/ja miceGranule layerCerebellar granule layerPostnatal day 8Cortical layers 2Cerebellar granule neuronsPostsynaptic density sizeSpectrin gene familyJaundiced miceMature mouse brainExchange transfusionHemolytic anemiaHemolytic pathologiesHematological consequencesMedial habenulaGranule neuronsFatal hemolytic anemiaDay 8Dentate gyrusNeuropsychiatric disordersSpectrin deficiencyWhite matterJa/jaMiceMouse brain
2021
Age-dependent ataxia and neurodegeneration caused by an αII spectrin mutation with impaired regulation of its calpain sensitivity
Miazek A, Zalas M, Skrzymowska J, Bogin BA, Grzymajło K, Goszczynski TM, Levine ZA, Morrow JS, Stankewich MC. Age-dependent ataxia and neurodegeneration caused by an αII spectrin mutation with impaired regulation of its calpain sensitivity. Scientific Reports 2021, 11: 7312. PMID: 33790315, PMCID: PMC8012654, DOI: 10.1038/s41598-021-86470-1.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsSpectrin cleavageCalpain cleavage sitesCalcium-activated proteaseGlobal neurodegenerationTraumatic encephalopathyC57BL/6J miceDendritic integrityExcessive activationNeuronal integrityProgressive ataxiaImpaired regulationCalpain activationCalpain sensitivityPhysiologic significanceNeurodegenerative diseasesNeuronal developmentCalpain proteolysisCalpain proteasesCalcium-dependent bindingAtaxiaNeurodegenerationCalpainActivated calpainSubstrate-level regulationCaM affinity
2017
βIII Spectrin Is Necessary for Formation of the Constricted Neck of Dendritic Spines and Regulation of Synaptic Activity in Neurons
Efimova N, Korobova F, Stankewich MC, Moberly AH, Stolz DB, Wang J, Kashina A, Ma M, Svitkina T. βIII Spectrin Is Necessary for Formation of the Constricted Neck of Dendritic Spines and Regulation of Synaptic Activity in Neurons. Journal Of Neuroscience 2017, 37: 6442-6459. PMID: 28576936, PMCID: PMC5511878, DOI: 10.1523/jneurosci.3520-16.2017.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsDendritic spinesSynaptic activitySpinocerebellar ataxia type 5Spine neckAberrant spine morphologyMushroom-shaped spinesType 5Autosomal recessive cerebellar ataxia type 1Spiny synapsesPostsynaptic excitationMiniature EPSCsShaft synapsesDamage neuronsNeuronal pathologyCortical neuronsSomatodendritic compartmentPresynaptic terminalsNeurodegenerative syndromePostsynaptic structuresSpine headsNeuropsychiatric disordersSynaptic strengthType 1Spine morphologyBrain function
2014
A hierarchy of ankyrin-spectrin complexes clusters sodium channels at nodes of Ranvier
Ho TS, Zollinger DR, Chang KJ, Xu M, Cooper EC, Stankewich MC, Bennett V, Rasband MN. A hierarchy of ankyrin-spectrin complexes clusters sodium channels at nodes of Ranvier. Nature Neuroscience 2014, 17: 1664-1672. PMID: 25362473, PMCID: PMC4271271, DOI: 10.1038/nn.3859.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and Concepts
2012
Intrinsic indicators for specimen degradation
Li J, Kil C, Considine K, Smarkucki B, Stankewich MC, Balgley B, Vortmeyer AO. Intrinsic indicators for specimen degradation. Laboratory Investigation 2012, 93: 242-253. PMID: 23212099, DOI: 10.1038/labinvest.2012.164.Peer-Reviewed Original ResearchCitationsA Distal Axonal Cytoskeleton Forms an Intra-Axonal Boundary that Controls Axon Initial Segment Assembly
Galiano MR, Jha S, Ho TS, Zhang C, Ogawa Y, Chang KJ, Stankewich MC, Mohler PJ, Rasband MN. A Distal Axonal Cytoskeleton Forms an Intra-Axonal Boundary that Controls Axon Initial Segment Assembly. Cell 2012, 149: 1125-1139. PMID: 22632975, PMCID: PMC3361702, DOI: 10.1016/j.cell.2012.03.039.Peer-Reviewed Original ResearchCitationsAltmetric
2011
Cell organization, growth, and neural and cardiac development require αII-spectrin
Stankewich MC, Cianci CD, Stabach PR, Ji L, Nath A, Morrow JS. Cell organization, growth, and neural and cardiac development require αII-spectrin. Journal Of Cell Science 2011, 124: 3956-3966. PMID: 22159418, PMCID: PMC3244980, DOI: 10.1242/jcs.080374.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsMeSH KeywordsActinsAnimalsAnkyrinsAxonsBody PatterningCarrier ProteinsCell MembraneCell PolarityCell ProliferationCraniofacial AbnormalitiesEmbryo, MammalianEmbryonic DevelopmentFemaleFibroblastsGene DeletionHeart Defects, CongenitalMaleMiceMice, Inbred C57BLMicrofilament ProteinsNeural Tube DefectsNeuroepithelial CellsPhenotypeProtein StabilityPseudopodiaSpectrinConceptsΑII-spectrinSteady-state protein levelsΒIII spectrinEmbryonic day 12.5Tissue patterningRenal epithelial cellsEmbryonic lethalCortical actinOrgan developmentAnkyrin BExon trappingEmbryonic fibroblastsTranscriptional levelΒ-spectrinCardiac developmentCell organizationCell spreadingAxon formationNeural tubeHeterozygous animalsTargeted disruptionApical membraneNeuroepithelial cellsDay 12.5Cell morphologySchwann cell spectrins modulate peripheral nerve myelination
Susuki K, Raphael AR, Ogawa Y, Stankewich MC, Peles E, Talbot WS, Rasband MN. Schwann cell spectrins modulate peripheral nerve myelination. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 8009-8014. PMID: 21518878, PMCID: PMC3093478, DOI: 10.1073/pnas.1019600108.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsSchwann cell cytoskeletonCell cytoskeletonΒII spectrinSubmembranous cytoskeletal proteinsNeuron-glia interactionsEfficient action potential propagationSchwann cellsMembrane proteinsCytoskeletal rearrangementsLoss of spectrinCytoskeletal proteinsNectin-like proteinsCell shapeContact sitesF-actinPeripheral nerve myelinationSpectrinPeripheral nerve developmentΑII-spectrinCytoskeletonProteinNerve myelinationNerve developmentMotor nervesCells
2010
Targeted deletion of βIII spectrin impairs synaptogenesis and generates ataxic and seizure phenotypes
Stankewich MC, Gwynn B, Ardito T, Ji L, Kim J, Robledo RF, Lux SE, Peters LL, Morrow JS. Targeted deletion of βIII spectrin impairs synaptogenesis and generates ataxic and seizure phenotypes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 6022-6027. PMID: 20231455, PMCID: PMC2851889, DOI: 10.1073/pnas.1001522107.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsBetaIII spectrinSpinocerebellar ataxia type 5Spectrin membrane skeletonTargeted gene disruptionAmino acid transportersExcitatory amino acid transportersImpairs synaptogenesisProtein traffickingSeizure disorderGene disruptionDark Purkinje cellsMembrane skeletonAlphaII-spectrinAcid transportersMechanistic basisPurkinje cellsMembrane channelsGlutamate receptor deltaIntracellular pathwaysSpectrin bindsSynaptic proteinsSpectrinReceptor deltaProteinGolgi profiles
2005
HSP70 binding modulates detachment of Na-K-ATPase following energy deprivation in renal epithelial cells
Riordan M, Sreedharan R, Wang S, Thulin G, Mann A, Stankewich M, Van Why S, Kashgarian M, Siegel NJ. HSP70 binding modulates detachment of Na-K-ATPase following energy deprivation in renal epithelial cells. American Journal Of Physiology. Renal Physiology 2005, 288: f1236-f1242. PMID: 15701813, DOI: 10.1152/ajprenal.00438.2004.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsRenal epithelial cellsATP depletionMolecular chaperone Hsp70Binding of Hsp70Na-K-ATPaseFundamental cellular mechanismsRenal epithelial polarityCultured renal epithelial cellsEpithelial cellsHeat shock protein 70Protein clathrinEpithelial polarityMolecular chaperonesOverexpression of HSP70Chaperone Hsp70Shock protein 70Energy deprivationLLC-PK1 cellsStress proteinsMolecular mechanismsHSP bindingHSP70Cell lysatesCellular mechanismsATP turnover
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