2024
Methylarginine targeting chimeras for lysosomal degradation of intracellular proteins
Seabrook L, Franco C, Loy C, Osman J, Fredlender C, Zimak J, Campos M, Nguyen S, Watson R, Levine S, Khalil M, Sumigray K, Trader D, Albrecht L. Methylarginine targeting chimeras for lysosomal degradation of intracellular proteins. Nature Chemical Biology 2024, 20: 1566-1576. PMID: 39414979, DOI: 10.1038/s41589-024-01741-y.Peer-Reviewed Original ResearchProtein arginine methyltransferasesTarget proteinsLoss-of-function phenotypesDegradation of intracellular proteinsUbiquitin-proteasome pathwayHistone deacetylase 6Bromodomain-containing protein 4Discovery of small moleculesTargeted protein degradationDegrade target proteinsTargeting chimerasArginine methylationArginine methyltransferasesProtein methylationPathogenic proteinsLysosomal deliveryLysosomal pathwayIntracellular proteinsLysosomal degradationHeterobifunctional small moleculesProtein degradationSmall-molecule degradersLysosomal proteolysisSubstrate degradationSmall molecules313 BEST4+ CFTR high expresser cells in normal rat are neuropods that sense and respond to luminal pH and are altered in dF508 CF intestine
Jin J, dos Reis D, Muiler C, Zagoren E, Donnelley M, Parsons D, Sumigray K, Ameen N. 313 BEST4+ CFTR high expresser cells in normal rat are neuropods that sense and respond to luminal pH and are altered in dF508 CF intestine. Journal Of Cystic Fibrosis 2024, 23: s167. DOI: 10.1016/s1569-1993(24)01153-6.Peer-Reviewed Original ResearchRedefining intestinal stemness: The emergence of a new ISC population
Li M, Sumigray K. Redefining intestinal stemness: The emergence of a new ISC population. Cell 2024, 187: 2900-2902. PMID: 38848673, DOI: 10.1016/j.cell.2024.04.021.Peer-Reviewed Original ResearchA Coculture System for Modeling Intestinal Epithelial-Fibroblast Crosstalk
Lee R, Li M, Figetakis M, Sumigray K. A Coculture System for Modeling Intestinal Epithelial-Fibroblast Crosstalk. Methods In Molecular Biology 2024, 1-16. PMID: 38700834, DOI: 10.1007/7651_2024_544.Peer-Reviewed Original Research978 CFTR HIGH EXPRESSER CELLS EXPRESS NEUROPOD GENES AND RESPOND TO ENVIRONMENTAL CUES IN THE INTESTINE
Jin J, Reis D, Muiler C, Sumigray K, Ameen N. 978 CFTR HIGH EXPRESSER CELLS EXPRESS NEUROPOD GENES AND RESPOND TO ENVIRONMENTAL CUES IN THE INTESTINE. Gastroenterology 2024, 166: s-236. DOI: 10.1016/s0016-5085(24)01027-8.Peer-Reviewed Original Research
2023
Generation and Manipulation of Rat Intestinal Organoids.
Zagoren E, Santos A, Ameen N, Sumigray K. Generation and Manipulation of Rat Intestinal Organoids. Journal Of Visualized Experiments 2023 PMID: 37427951, DOI: 10.3791/65343.Peer-Reviewed Original ResearchAntibiotic-induced microbial depletion enhances murine small intestinal epithelial growth in a serotonin-dependent manner
Salvi P, Shaughnessy M, Sumigray K, Cowles R. Antibiotic-induced microbial depletion enhances murine small intestinal epithelial growth in a serotonin-dependent manner. AJP Gastrointestinal And Liver Physiology 2023, 325: g80-g91. PMID: 37158470, DOI: 10.1152/ajpgi.00113.2022.Peer-Reviewed Original ResearchConceptsSerotonin activitySERT protein expressionSerotonin potentiationEpithelial proliferationSerotonin transporterEndogenous serotoninVillus heightMicrobial depletionIntestinal epithelial growthProtein expressionEpithelial growthSerotonin-dependent mechanismIntestinal villus heightSmall intestine resultsIntestinal surface areaSmall intestinal villiSmall intestinal cryptsIntestinal pathologyPara-chlorophenylalanineISC numbersSerotonin synthesisIntestinal homeostasisEpithelial expressionMouse modelAnimal modelsSa1225 BIFUNCTIONALITY OF UNCONVENTIONAL MYOSIN 5B (MYO5B) IN INTESTINAL PHYSIOLOGY: ROLE IN MVID AND GENERATION OF CFTR HIGH EXPRESSER (CHE) CELLS IN MICE.
Santos A, dos Reis D, Sumigray K, Ameen N. Sa1225 BIFUNCTIONALITY OF UNCONVENTIONAL MYOSIN 5B (MYO5B) IN INTESTINAL PHYSIOLOGY: ROLE IN MVID AND GENERATION OF CFTR HIGH EXPRESSER (CHE) CELLS IN MICE. Gastroenterology 2023, 164: s-331. DOI: 10.1016/s0016-5085(23)01758-4.Peer-Reviewed Original ResearchVibrio cholerae biofilms use modular adhesins with glycan-targeting and nonspecific surface binding domains for colonization
Huang X, Nero T, Weerasekera R, Matej K, Hinbest A, Jiang Z, Lee R, Wu L, Chak C, Nijjer J, Gibaldi I, Yang H, Gamble N, Ng W, Malaker S, Sumigray K, Olson R, Yan J. Vibrio cholerae biofilms use modular adhesins with glycan-targeting and nonspecific surface binding domains for colonization. Nature Communications 2023, 14: 2104. PMID: 37055389, PMCID: PMC10102183, DOI: 10.1038/s41467-023-37660-0.Peer-Reviewed Original ResearchConceptsBiofilm matrix exopolysaccharideFacilitate host colonizationVibrio cholerae biofilmsΒ-propeller domainMatrix exopolysaccharideModular domainsHost colonizationRedundant rolesDistinct functionsAbiotic surfacesAdhesive proteinsHost surfaceHuman pathogensVibrio choleraeAdhesinsBacterial biofilmsHost tissuesColonization modelColonizationBAP1BiofilmsPathogensAntibiotic resistanceRBMCDomainCFTR High Expresser Cells in cystic fibrosis and intestinal diseases
dos Reis D, Dastoor P, Santos A, Sumigray K, Ameen N. CFTR High Expresser Cells in cystic fibrosis and intestinal diseases. Heliyon 2023, 9: e14568. PMID: 36967909, PMCID: PMC10031467, DOI: 10.1016/j.heliyon.2023.e14568.Peer-Reviewed Original ResearchCystic fibrosisIntestinal diseaseCystic fibrosis transmembrane conductance regulatorQuality of lifeIntestinal dysfunctionGastrointestinal diseasesIntestinal physiologyFibrosisDiseasePathophysiologyFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorCFTR leadConductance regulator
2022
Maf family transcription factors are required for nutrient uptake in the mouse neonatal gut
Bara A, Chen L, Ma C, Underwood J, Moreci R, Sumigray K, Sun T, Diao Y, Verzi M, Lechler T. Maf family transcription factors are required for nutrient uptake in the mouse neonatal gut. Development 2022, 149 PMID: 36504079, PMCID: PMC10112929, DOI: 10.1242/dev.201251.Peer-Reviewed Original ResearchConceptsNutrient uptakeTranscription factorsMaf family transcription factorsMajor transcriptional changesFamily transcription factorsLoss of Blimp1Transcription factor MafBMaf proteinsCell fateTranscriptional regulatorsTranscriptional changesRNA-seqMaster regulatorEnterocyte genesFatty acid oxidationGene expressionPeroxisome numberAdult intestineMetabolic pathwaysMolecular componentsSubsequent degradationMaf factorsC-MafSimilar defectsIntestinal enterocytesLoss of Serum Glucocorticoid-Inducible Kinase 1 SGK1 Worsens Malabsorption and Diarrhea in Microvillus Inclusion Disease (MVID)
Ahsan K, dos Reis DC, Barbieri A, Sumigray KD, Nottoli T, Salas PJ, Ameen NA. Loss of Serum Glucocorticoid-Inducible Kinase 1 SGK1 Worsens Malabsorption and Diarrhea in Microvillus Inclusion Disease (MVID). Journal Of Clinical Medicine 2022, 11: 4179. PMID: 35887942, PMCID: PMC9319011, DOI: 10.3390/jcm11144179.Peer-Reviewed Original ResearchMicrovillus inclusion diseaseSevere diarrheaInclusion diseaseFluid secretionCystic fibrosis transmembrane conductance regulatorDouble knockout miceMicrovillus inclusionsGlucocorticoid-inducible kinase 1Carbohydrate malabsorptionKnockout miceIntestinal carbohydrateDiarrheaDiarrheal diseaseMalabsorptionMiceVillus enterocytesDiseaseLoss of MYO5BFunction mutationsApical cystic fibrosis transmembrane conductance regulatorFibrosis transmembrane conductance regulatorKinase 1SecretionIntestineTransmembrane conductance regulatorSerum and Glucocorticoid‐Inducible Kinase 1 (SGK1): An Important Contributor to Diarrhea and Malabsorption in Microvillus Inclusion Disease (MVID)
Ahsan K, dos Reis D, Barbieri A, Sumigray K, Nottoli T, Salas P, Ameen N. Serum and Glucocorticoid‐Inducible Kinase 1 (SGK1): An Important Contributor to Diarrhea and Malabsorption in Microvillus Inclusion Disease (MVID). The FASEB Journal 2022, 36 DOI: 10.1096/fasebj.2022.36.s1.r5730.Peer-Reviewed Original ResearchMicrovillus inclusion diseaseGlucocorticoid-inducible kinase 1Severe diarrheaF miceInclusion diseaseCystic fibrosis transmembrane conductance regulatorFluid secretionWorsening of diarrheaMicrovillus inclusionsPhosphorylation of PDK1Kinase 1Intestinal lysatesSGK1 pathwayCarbohydrate malabsorptionER miceTamoxifen inductionBeta-ENaCDiarrheaDiarrheal diseaseSmall intestineMalabsorptionMiceDCKO miceGlucose lossPhosphorylation of SGK1
2019
Lysosome-Rich Enterocytes Mediate Protein Absorption in the Vertebrate Gut
Park J, Levic DS, Sumigray KD, Bagwell J, Eroglu O, Block CL, Eroglu C, Barry R, Lickwar CR, Rawls JF, Watts SA, Lechler T, Bagnat M. Lysosome-Rich Enterocytes Mediate Protein Absorption in the Vertebrate Gut. Developmental Cell 2019, 51: 7-20.e6. PMID: 31474562, PMCID: PMC6783362, DOI: 10.1016/j.devcel.2019.08.001.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportAnimalsApoptosis Regulatory ProteinsDietary ProteinsDisease Models, AnimalEnterocytesFemaleGastrointestinal MicrobiomeGene DeletionGene Expression Regulation, DevelopmentalIleumIntestinal AbsorptionIntestinesKwashiorkorLigandsLysosomesMaleMembrane ProteinsMiceReceptors, Cell SurfaceZebrafishZebrafish ProteinsConceptsFluid-phase endocytosisEndocytic machineryTrans-cellular transportLuminal protein digestionVertebrate gutLarval zebrafishCritical developmental stagesStomachless fishMolecular mechanismsVertebrate growthProtein uptakeDevelopmental stagesIntracellular digestionProtein digestionConditional deletionStunted growthIntestinal cellsOral acquisitionDab2Dietary proteinSevere protein malnutritionDigestive functionNeonatal mammalsProteinMalnutrition syndrome
2018
Cellular Dynamics Driving Elongation of the Gut
Sumigray K, Lechler T. Cellular Dynamics Driving Elongation of the Gut. Developmental Cell 2018, 46: 127-128. PMID: 30016614, DOI: 10.1016/j.devcel.2018.06.027.Peer-Reviewed Original ResearchMorphogenesis and Compartmentalization of the Intestinal Crypt
Sumigray KD, Terwilliger M, Lechler T. Morphogenesis and Compartmentalization of the Intestinal Crypt. Developmental Cell 2018, 45: 183-197.e5. PMID: 29689194, PMCID: PMC5987226, DOI: 10.1016/j.devcel.2018.03.024.Peer-Reviewed Original ResearchConceptsRac1 null miceAdult mammalian intestineCell shape changesProgenitor cellsStem cell nicheGene networksCrypt morphogenesisCrypt progenitor cellsEssential regulatorMammalian intestineCell nicheGenetic analysisUnexpected roleApical constrictionNiche formationHemidesmosomal adhesionCrypt developmentTissue architectureMouse cryptsMorphogenesisAbsorptive villiNull miceIntestinal cryptsQuantitative morphometricsShape changesSpine Patterning Is Guided by Segmentation of the Notochord Sheath
Wopat S, Bagwell J, Sumigray KD, Dickson AL, Huitema LFA, Poss KD, Schulte-Merker S, Bagnat M. Spine Patterning Is Guided by Segmentation of the Notochord Sheath. Cell Reports 2018, 22: 2026-2038. PMID: 29466731, PMCID: PMC5860813, DOI: 10.1016/j.celrep.2018.01.084.Peer-Reviewed Original ResearchConceptsNotochord sheathTissue-specific manipulationActivation of NotchZebrafish notochordCentrum formationVertebral patterningOuter epithelial cell layerSheath cellsSegmentation defectsAxial structuresEpithelial cell layerNotochordPatterningIVD areaZebrafish spineDomainCell layerNotchCentraOsteoblastsSheathCellsActivationRap1 acts via multiple mechanisms to position Canoe and adherens junctions and mediate apical-basal polarity establishment
Bonello TT, Perez-Vale KZ, Sumigray KD, Peifer M. Rap1 acts via multiple mechanisms to position Canoe and adherens junctions and mediate apical-basal polarity establishment. Development 2018, 145: dev157941. PMID: 29361565, PMCID: PMC5825837, DOI: 10.1242/dev.157941.Peer-Reviewed Original ResearchMeSH KeywordsAdherens JunctionsAnimalsAnimals, Genetically ModifiedCell PolarityDrosophila melanogasterDrosophila ProteinsFemaleGastrulationGene Knockdown TechniquesGuanine Nucleotide Exchange FactorsIntracellular Signaling Peptides and ProteinsMaleModels, BiologicalProtein Interaction Domains and MotifsProtein TransportRNA InterferenceShelterin ComplexTelomere-Binding ProteinsConceptsApical-basal polarityPolarity establishmentMembrane localizationEpithelial apical-basal polarityAdherens junction positioningBazooka/Par3Adherens junction assemblyMost animal tissuesSmall GTPase Rap1Polarity initiationApical retentionNascent junctionsRA domainJunction assemblyAdherens junctionsTricellular junctionsPolarized cellsGTPase Rap1Macromolecular assembliesApical activationRap1Spatial organizationAnimal tissuesMultiple mechanismsEstablishment model
2016
Abelson kinase acts as a robust, multifunctional scaffold in regulating embryonic morphogenesis
Rogers EM, Spracklen AJ, Bilancia CG, Sumigray KD, Allred SC, Nowotarski SH, Schaefer KN, Ritchie BJ, Peifer M. Abelson kinase acts as a robust, multifunctional scaffold in regulating embryonic morphogenesis. Molecular Biology Of The Cell 2016, 27: 2613-2631. PMID: 27385341, PMCID: PMC4985262, DOI: 10.1091/mbc.e16-05-0292.Peer-Reviewed Original ResearchConceptsF-actin-binding domainCell biological rolesCell shape changesDifferent protein motifsSeries of mutantsTyrosine kinase domainAbl functionActin regulationDrosophila morphogenesisEmbryonic morphogenesisProtein motifsAbelson familyPXXP motifInteraction domainKinase domainAbelson kinaseLinker regionKey regulatorAbl SH3Biological roleCellular behaviorMorphogenesisCell behaviorNormal developmentSH3
2015
The Arp2/3 complex has essential roles in vesicle trafficking and transcytosis in the mammalian small intestine
Zhou K, Sumigray KD, Lechler T. The Arp2/3 complex has essential roles in vesicle trafficking and transcytosis in the mammalian small intestine. Molecular Biology Of The Cell 2015, 26: 1995-2004. PMID: 25833710, PMCID: PMC4472011, DOI: 10.1091/mbc.e14-10-1481.Peer-Reviewed Original ResearchConceptsArp2/3 complexVesicle traffickingCell type-specific phenotypesCortical F-actinF-actin assemblyEssential roleMammalian small intestineF-actin filamentsCell polarityEndolysosomal systemEssential functionsF-actinCortical poolCell migrationCultured cellsIntestinal developmentTraffickingIntestinal epitheliumPhenotypeWide arrayComplexesComplex functionsTranscytosisLipid absorptionTranscytosis of IgG