Kristopher Kahle, MD, PhD
Assistant Professor AdjunctCards
About
Research
Publications
2025
Animal models of Chiari malformation types 1 and 2: Mechanistic insights and translational challenges
Davalan W, Li Q, Hale A, Fan B, Duy P, Mehta N, Alper S, Kundishora A, Muñoz W, Dennis E, Allington G, Mekbib K, Butler W, Kahle K. Animal models of Chiari malformation types 1 and 2: Mechanistic insights and translational challenges. Experimental Neurology 2025, 395: 115473. PMID: 40992613, DOI: 10.1016/j.expneurol.2025.115473.Peer-Reviewed Original ResearchChiari malformationAnimal modelsCerebrospinal fluidChiari malformation type 1Review of animal modelsEtiology-specific therapyPreclinical animal modelsNeural tube defectsCranial base developmentCM pathogenesisFetal sheepCSF leakagePrenatal treatmentNeural tube closureTube defectsSpontaneous modelPathophysiological insightsTranslational relevanceType 1Cerebellar herniationHuman patientsSurgical modelCerebrospinal fluid physiologyTranslational challengesTranslational importanceThe RNA-binding protein TRIM71 is essential for hearing in humans and mice and times auditory sensory organ development.
Li X, Morgan C, Duy P, Evsen L, Hao L, Machavoine R, Belhous K, Ernest S, Denoyelle F, Mignot C, Brioude F, Parodi M, Li L, Huang H, Nadar Ponniah P, Kolanus W, Kahle K, Marlin S, Doetzlhofer A. The RNA-binding protein TRIM71 is essential for hearing in humans and mice and times auditory sensory organ development. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2505811122. PMID: 40892928, PMCID: PMC12435228, DOI: 10.1073/pnas.2505811122.Peer-Reviewed Original ResearchConceptsKnockout miceAssociated with hearing lossMonoallelic missense mutationsTiming of cell cycle exitHair cellsCochlear progenitor cellsSensory organ developmentInner ear morphogenesisStereotypic timeCell cycle exitOuter hair cell regionHair cell regionMechanosensory hair cellsSevere HLHair cell progenitorsHearing deficitsEarly otic developmentProgenitor cellsAuditory sensory organCell progenitorsEar morphogenesisGenetic studiesMissense mutationsCycle exitRisk genesLetter: Modulation of PI3K and MEK Signaling Reverse Vein of Galen Malformation
Hale A, Kahle K. Letter: Modulation of PI3K and MEK Signaling Reverse Vein of Galen Malformation. Neurosurgery 2025, 97: e134-e135. PMID: 40767514, DOI: 10.1227/neu.0000000000003681.Peer-Reviewed Original ResearchAn opportune time for targeted brain arteriovenous malformation therapy.
Hale A, Kalailingam P, Kundishora A, Reeves B, Brastianos P, Shih H, Jain R, Ning M, Stapleton C, Patel A, Smith E, Chapman P, Rabinov J, Kleinstiver B, Musolino P, Kahle K. An opportune time for targeted brain arteriovenous malformation therapy. Journal Of Neurosurgery 2025, 1-4. PMID: 40644723, PMCID: PMC12477702, DOI: 10.3171/2025.4.jns25260.Peer-Reviewed Original ResearchMolecular hallmarks of hydrocephalus
Hale A, Zhou B, Rajan A, Duy P, Goolam M, Alper S, Lehtinen M, Lancaster M, Fame R, Kahle K. Molecular hallmarks of hydrocephalus. Science Translational Medicine 2025, 17: eadq1810. PMID: 40465691, PMCID: PMC12316480, DOI: 10.1126/scitranslmed.adq1810.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidBrain-CSF interfacePluripotent stem cell-derived cerebral organoidsStem cell dysfunctionAssociated with dilatationDisrupts synaptogenesisNeural stem cell dysfunctionMolecular classificationPharmacological treatmentCell dysfunctionImpaired neurogenesisBiomechanical instabilityHC subtypesGenome-widePleiotropic mechanismsCSF dynamicsNeural circuitryHydrocephalusEnvironmental insultsCerebral organoidsNeurodevelopmental comorbiditiesSingle-cell elderly blood–CSF atlas implicates peripherally influenced immune dysregulation in normal pressure hydrocephalus
Duy P, Kiziltug E, Greenberg A, Mehta N, Hao L, Fortes C, Mullany S, Fan B, Manichaikul A, Teich A, Chan D, Alper S, Hyman B, Arnold S, McKhann G, Frosch M, Kahle K. Single-cell elderly blood–CSF atlas implicates peripherally influenced immune dysregulation in normal pressure hydrocephalus. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2412159122. PMID: 40324076, PMCID: PMC12087963, DOI: 10.1073/pnas.2412159122.Peer-Reviewed Original ResearchConceptsIdiopathic normal pressure hydrocephalusNormal pressure hydrocephalusImmune dysregulationPeripheral bloodPressure hydrocephalusIdiopathic normal pressure hydrocephalus patientsProinflammatory alterationsVentricular CSFSingle-cell transcriptomicsINPH patientsCell populationsPatientsNeuroglial cellsCSFBloodHydrocephalusBaseline cognitive functionCognitive functionDysregulationMonocytesClinical phenotypes among patients with familial forms of Chiari malformation type 1.
Mekbib K, Muñoz W, Allington G, Zhao S, Mehta N, Fortes C, Shohfi J, Fan B, Nelson-Williams C, DeSpenza T, Butler W, Alper S, Jackson E, Kahle K. Clinical phenotypes among patients with familial forms of Chiari malformation type 1. Journal Of Neurosurgery Pediatrics 2025, 36: 109-118. PMID: 40315599, DOI: 10.3171/2025.1.peds24187.Peer-Reviewed Original ResearchConceptsChiari malformation type 1Connective tissue disordersClinical phenotypeNeurological comorbiditiesType 1Family membersCerebellar tonsillar herniationPatient-parent triosEhlers-Danlos syndromeWhole-exome sequencingNeck painTonsillar herniationCraniocervical junctionNeural compressionCSF obstructionTissue disordersUnivariate analysisCohort studyFamily historyClinical symptomsNeurosurgical managementNeurodevelopmental conditionsVariable symptomsForamen magnumPatientsNon-syndromic craniosynostosis
Alperovich M, Tonello C, Mayes L, Kahle K. Non-syndromic craniosynostosis. Nature Reviews Disease Primers 2025, 11: 24. PMID: 40210850, DOI: 10.1038/s41572-025-00607-4.Peer-Reviewed Original ResearchConceptsNon-syndromic craniosynostosisSurgical techniqueOptimal timing of surgeryHealth-care disparitiesQuality of life outcomesDelayed initial presentationPatient-reported quality of life outcomesCranial suturesTime of surgeryCranial vault remodelingAbnormal head shapeSpring-assisted cranioplastyIncreased intracranial pressurePatient-reported qualitySchool-aged childrenInitial presentationSurgical interventionVault remodelingStrip craniectomyPhysical examinationCompare outcomesSchool-agePremature fusionMesenchymal stem cellsIntracranial pressureLarge Cohort Integrative Multiomic Analyses Identifies Novel Risk Genes for Congenital Cerebral Ventriculomegaly and Characterizes Distinct Spatiotemporal Clusters of Pathogenesis (S31.002)
Allington G, Mekbib K, Dennis E, Miyagishima D, Kahle K. Large Cohort Integrative Multiomic Analyses Identifies Novel Risk Genes for Congenital Cerebral Ventriculomegaly and Characterizes Distinct Spatiotemporal Clusters of Pathogenesis (S31.002). Neurology 2025, 104 DOI: 10.1212/wnl.0000000000208710.Peer-Reviewed Original Research2096 Cerebellar Overgrowth Subtype of Chiari Malformation Type 1 and Genetic Dysregulation of PI3K Signaling
Mekbib K, Munoz W, Allington G, McGee S, Kiziltug E, DeSpenza T, Fortes C, Nelson-Williams C, Mehta N, Smith H, Zhao S, Shofi J, Ocken J, Reeves B, Greenberg A, Kundishora A, Moreno-De-Luca A, Jin S, Alper S, Lifton R, Butler W, Kahle K. 2096 Cerebellar Overgrowth Subtype of Chiari Malformation Type 1 and Genetic Dysregulation of PI3K Signaling. Neurosurgery 2025, 71: 272-272. DOI: 10.1227/neu.0000000000003360_2096.Peer-Reviewed Original ResearchDe novo variantsChiari malformation type 1PI3K signaling pathwaySingle-cell RNA-seq datasetsExome-wide significancePatient-parent triosRNA-seq datasetsGenetic dysregulationGene ontology analysisPI3K signalingPI3K enzymesPI3K pathwayExome-wideDysregulation of PI3K signalingGene setsTranscriptomic atlasOntology analysisType 1Phenotypic characterizationObstruction of CSF flowCompression of neural tissueGenesK signalingK pathwayMultiple variants
Clinical Trials
Current Trials
Pediatric Genomics Discovery Program (PGDP)
HIC ID1411014977RoleSub InvestigatorPrimary Completion Date12/31/2023Recruiting ParticipantsGenderBoth
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Neurosurgery
789 Howard Avenue, Tompkins 4
New Haven, CT 06520
United States