Timothy Nottoli, PhD
Senior Research Scientist in Comparative MedicineCards
About
Research
Publications
2025
GDF3 promotes adipose tissue macrophage-mediated inflammation via altered chromatin accessibility during aging
Jang I, Carey A, Kruglov V, Nguyen K, Misialek J, Cholensky S, Smith D, Bai S, Nottoli T, Bernlohr D, Lutsey P, Camell C. GDF3 promotes adipose tissue macrophage-mediated inflammation via altered chromatin accessibility during aging. Nature Aging 2025, 1-16. PMID: 41398392, DOI: 10.1038/s43587-025-01034-6.Peer-Reviewed Original ResearchAdipose tissue macrophage phenotypeSusceptibility to endotoxemiaTissue macrophage phenotypeAdipose tissue macrophagesMacrophage-related inflammationMacrophage-mediated inflammationAge-dependent increaseInflammatory phenotypeProinflammatory macrophagesInflammatory stateOld miceSingle-cell RNA sequencingTissue macrophagesMacrophage phenotypePharmacological interventionsInflammationAdipose tissue samplesEndotoxemiaTherapeutic targetMacrophagesTissue samplesTransposase-accessible chromatinAtherosclerosis RiskAgeChromatin accessibilityA versatile cohesion manipulation system probes female reproductive age-related egg aneuploidy
Leem J, Lemonnier T, Khutsaidze A, Tian L, Xing X, Bai S, Nottoli T, Mogessie B. A versatile cohesion manipulation system probes female reproductive age-related egg aneuploidy. Nature Aging 2025, 5: 2215-2227. PMID: 41184483, PMCID: PMC12618256, DOI: 10.1038/s43587-025-00997-w.Peer-Reviewed Original ResearchConceptsAneuploidy rateReproductive agePremature lossChromatid separationOlder reproductive agePremature sister chromatid separationLiving mouse oocytesWoman's reproductive lifespanSister chromatid separationHigh-resolution live imagingChromosomal abnormalitiesFemale reproductive agingMaternal ageMouse oocytesSeparation of chromosomesAneuploidy developmentMeiotic cohesin Rec8Multifactorial mechanismsEgg aneuploidyDose-dependent degradationCentromere dysfunctionCohesion proteinsAneuploidyCytoskeletal defectsCohesin Rec8GDF3 promotes adipose tissue macrophage-mediated inflammation via altered chromatin accessibility during aging 4428
Jang I, Carey A, Kruglov V, Cholensky S, Smith D, Bai S, Nottoli T, Bernlohr D, Camell C. GDF3 promotes adipose tissue macrophage-mediated inflammation via altered chromatin accessibility during aging 4428. The Journal Of Immunology 2025, 214 DOI: 10.1093/jimmun/vkaf283.2112.Peer-Reviewed Original ResearchAdipose tissue macrophagesMyeloid-specific deletionInflammatory phenotypeOld miceSusceptibility to endotoxemiaATAC sequencingInhibitor of Smad3Hyperactivation of macrophagesMacrophage-mediated inflammationInflammatory stateAdipose expansionChromatin accessibilityInflammatory cytokinesNLRP3 inflammasome activationTissue macrophagesTop-regulated genesNational InstituteInflammatory responseInflammationEndotoxemiaHuman ATMacrophagesTherapeutic targetMiceInflammasome activationAuthor Correction: CpG island turnover events predict evolutionary changes in enhancer activity
Kocher A, Dutrow E, Uebbing S, Yim K, Larios M, Baumgartner M, Nottoli T, Noonan J. Author Correction: CpG island turnover events predict evolutionary changes in enhancer activity. Genome Biology 2025, 26: 363. PMID: 41126355, PMCID: PMC12548154, DOI: 10.1186/s13059-025-03834-w.Peer-Reviewed Original ResearchCell-type-specific dysregulation of gene expression due to Chd8 haploinsufficiency during mouse cortical development
Yim K, Baumgartner M, Krenzer M, Larios M, Hill-Terán G, Nottoli T, Muhle R, Noonan J. Cell-type-specific dysregulation of gene expression due to Chd8 haploinsufficiency during mouse cortical development. Cell Genomics 2025, 5: 100986. PMID: 40967226, PMCID: PMC12648110, DOI: 10.1016/j.xgen.2025.100986.Peer-Reviewed Original ResearchCHD8 haploinsufficiencyGenes associated with neurodevelopmental disordersExcitatory cortical neuronsAssociated with riskRisk-associated genesSingle-nucleus RNA sequencingEmbryonic radial gliaNeurodevelopmental gene expressionNeuron projection developmentCortical plateDisruptive variantsImpaired synaptogenesisChromatin remodelingSynaptic activityMouse cortical developmentMature neuronsCortical developmentNeuronal lineageHaploinsufficiencyCortical neuronsRNA sequencingSingle-nucleusProgenitor zoneGene expressionRadial gliaHeterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice
Ishchenko Y, Jeng A, Feng S, Nottoli T, Manriquez-Rodriguez C, Nguyen K, Carrizales M, Vitarelli M, Corcoran E, Greer C, Myers S, Koleske A. Heterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice. ELife 2025, 13: rp103620. PMID: 40488445, PMCID: PMC12148328, DOI: 10.7554/elife.103620.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderGuanine nucleotide exchange factorNeurodevelopmental disordersPresynaptic glutamate releaseLayer 5 pyramidal neuronsAssociated with neurodevelopmental disordersIntellectual disabilitySpectrum disorderMouse behaviorCognitive behaviorNucleotide exchange factorNeuronal developmentBrain developmentGlutamate releaseIncreased Rac1 activityBrain sizeSynaptic functionControlling neuronal developmentSchizophreniaImpaired abilityAssociated with increased levelsNeurodevelopmental eventsActive GTPaseGEF Tiam1Exchange factorHeterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice
Ishchenko Y, Jeng A, Feng S, Nottoli T, Manriquez-Rodriguez C, Nguyen K, Carrizales M, Vitarelli M, Corcoran E, Greer C, Myers S, Koleske A. Heterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice. ELife 2025, 13 DOI: 10.7554/elife.103620.3.Peer-Reviewed Original ResearchAutism spectrum disorderGuanine nucleotide exchange factorNeurodevelopmental disordersPresynaptic glutamate releaseLayer 5 pyramidal neuronsAssociated with neurodevelopmental disordersIntellectual disabilitySpectrum disorderMouse behaviorCognitive behaviorNucleotide exchange factorSchizophreniaNeuronal developmentBrain developmentGlutamate releaseIncreased Rac1 activityBrain sizeSynaptic functionControlling neuronal developmentImpaired abilityAssociated with increased levelsNeurodevelopmental eventsActive GTPaseGEF Tiam1Exchange factorCas12a-knock-in mice for multiplexed genome editing, disease modelling and immune-cell engineering
Tang K, Zhou L, Tian X, Fang S, Vandenbulcke E, Du A, Shen J, Cao H, Zhou J, Chen K, Kim H, Luo Z, Xin S, Lin S, Park D, Yang L, Zhang Y, Suzuki K, Majety M, Ling X, Lam S, Chow R, Ren P, Tao B, Li K, Codina A, Dai X, Shang X, Bai S, Nottoli T, Levchenko A, Booth C, Liu C, Fan R, Dong M, Zhou X, Chen S. Cas12a-knock-in mice for multiplexed genome editing, disease modelling and immune-cell engineering. Nature Biomedical Engineering 2025, 9: 1290-1308. PMID: 40114032, PMCID: PMC12360953, DOI: 10.1038/s41551-025-01371-2.Peer-Reviewed Original ResearchKnock-In MiceBone marrow-derived dendritic cellsCD8+ T cellsNon-viral delivery vehiclesAdeno-associated virusDisease modelsCD4+Dendritic cellsC57BL/6 backgroundT cellsConstitutive expressionB cellsLipid nanoparticlesEx vivoGenome editingMiceMultiplex genome engineeringROSA26 locusGene interaction networksMultiplex genome editingLiver tissueTargeted genome editingDiseaseDelivery vehiclesCRISPR RNA
2024
65 High-fidelity enhanced AsCas12a knock-in mice for efficient multiplexed gene editing, disease modeling and orthogonal immunogenetics
Tang K, Zhou X, Fang S, Vandenbulcke E, Du A, Shen J, Cao H, Zhou J, Chen K, Xin S, Zhou L, Lin S, Majety M, Lin X, Lam S, Chow R, Bai S, Nottoli T, Booth C, Liu C, Dong M, Chen S. 65 High-fidelity enhanced AsCas12a knock-in mice for efficient multiplexed gene editing, disease modeling and orthogonal immunogenetics. 2024, a72-a72. DOI: 10.1136/jitc-2024-sitc2024.0065.Peer-Reviewed Original ResearchEvolutionary Innovations in Conserved Regulatory Elements Associate With Developmental Genes in Mammals
Uebbing S, Kocher A, Baumgartner M, Ji Y, Bai S, Xing X, Nottoli T, Noonan J. Evolutionary Innovations in Conserved Regulatory Elements Associate With Developmental Genes in Mammals. Molecular Biology And Evolution 2024, 41: msae199. PMID: 39302728, PMCID: PMC11465374, DOI: 10.1093/molbev/msae199.Peer-Reviewed Original ResearchSequence evolutionRegulatory evolutionDevelopmental signaling genesEnhanced evolutionEvolutionary innovationMammalian phylogenyTranscriptional enhancersGenetic variationPhenotypic variationPleiotropic genesDevelopmental genesEnhancer elementsHoofed mammalsEnhancer sequencesActivation domainSignaling GenesEvolutionary adaptationDiverse organismsGenesHuman diseasesRegulatory functionsDevelopmental processesDeveloping limbCell typesMammals
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