Kristopher Kahle, MD, PhD
Assistant Professor AdjunctCards
About
Research
Publications
2025
Molecular 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, 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 variantsTransient Receptor Potential channels (TRP) in GtoPdb v.2025.1
Blair N, McKemy D, Nilius B, Oancea E, Owsianik G, Riccio A, Sah R, Stotz S, Tian J, Tong D, Vriens J, Wu L, Xu H, Yang F, Yang W, Yue L, Liu Q, Liu B, Caceres A, Carvacho I, Chaudhuri D, Clapham D, De Clercq K, Delling M, Doerner J, Fan L, Grimm C, Ha K, Hu M, Jabba S, Jordt S, Julius D, Kahle K, Zhu M. Transient Receptor Potential channels (TRP) in GtoPdb v.2025.1. IUPHAR/BPS Guide To Pharmacology CITE 2025, 2025 DOI: 10.2218/gtopdb/f78/2025.1.Peer-Reviewed Original ResearchTRPC channelsTransient receptor potential channelsCongenital stationary night blindnessCalcium-activated cationStore-operated channelsAdenosine diphosphate riboseNumerous splice variantsNMDA receptorsActivate TRPA1Intracellular ATP levelsCation channelsChannel activityMicromolar concentrations of La3+Mucolipidosis type IVNeurodegenerative disorder mucolipidosis type IVDepletion of intracellular calcium storesTRP channelsRegulation of Ca2+ entryAssociated with conduction defectsDetection of noxious heatDevelopment of heat hyperalgesiaDevelopment of thermal hyperalgesiaDynamic intracellular vesicular structuresExtra-synaptic NMDA receptorsInvolvement of TRP channelsPTEN mutations impair CSF dynamics and cortical networks by dysregulating periventricular neural progenitors
DeSpenza T, Kiziltug E, Allington G, Barson D, McGee S, O’Connor D, Robert S, Mekbib K, Nanda P, Greenberg A, Singh A, Duy P, Mandino F, Zhao S, Lynn A, Reeves B, Marlier A, Getz S, Nelson-Williams C, Shimelis H, Walsh L, Zhang J, Wang W, Prina M, OuYang A, Abdulkareem A, Smith H, Shohfi J, Mehta N, Dennis E, Reduron L, Hong J, Butler W, Carter B, Deniz E, Lake E, Constable R, Sahin M, Srivastava S, Winden K, Hoffman E, Carlson M, Gunel M, Lifton R, Alper S, Jin S, Crair M, Moreno-De-Luca A, Luikart B, Kahle K. PTEN mutations impair CSF dynamics and cortical networks by dysregulating periventricular neural progenitors. Nature Neuroscience 2025, 28: 536-557. PMID: 39994410, PMCID: PMC12038823, DOI: 10.1038/s41593-024-01865-3.Peer-Reviewed Original ResearchConceptsNeural progenitor cellsCongenital hydrocephalusCSF dynamicsIncreased CSF productionDe novo mutationsFrequent monogenic causeEverolimus treatmentCSF shuntingNonsurgical treatmentPTEN mutationsAqueductal stenosisInhibitory interneuronsVentriculomegalyProgenitor cellsChoroid plexusMonogenic causeCortical networksIncreased survivalBrain ventriclesCortical deficitsNeural progenitorsGene PTENCSF productionNkx2.1PTENUnbiased CSF Proteomics in Patients With Idiopathic Normal Pressure Hydrocephalus to Identify Molecular Signatures and Candidate Biomarkers
de Geus M, Wu C, Dodge H, Leslie S, Wang W, Lam T, Kahle K, Chan D, Kivisäkk P, Nairn A, Arnold S, Carlyle B. Unbiased CSF Proteomics in Patients With Idiopathic Normal Pressure Hydrocephalus to Identify Molecular Signatures and Candidate Biomarkers. Neurology 2025, 104: e213375. PMID: 39951680, PMCID: PMC11837848, DOI: 10.1212/wnl.0000000000213375.Peer-Reviewed Original ResearchConceptsNeuronal pentraxin receptorIdiopathic normal pressure hydrocephalusTranscriptome dataAlzheimer's diseaseDifferential expression of proteinsGene ontology analysisDifferential expression analysisGene set enrichment analysisDownregulation of proteinsDifferentially expressed proteinsNormal pressure hydrocephalusBiological process enrichmentExpression of proteinsPotential disease biomarkersOntology analysisProteomic analysis of CSFPathophysiology of idiopathic normal pressure hydrocephalusProteomic analysisProteomic studiesProcess of immune responseEnrichment analysisExpression analysisPressure hydrocephalusDifferential expressionDiagnosis of idiopathic normal pressure hydrocephalus
2024
Congenital Spinal Meningocele
Parker T, Kahle K. Congenital Spinal Meningocele. New England Journal Of Medicine 2024, 392 PMID: 39752559, DOI: 10.1056/nejmicm2410556.Peer-Reviewed Original Research
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
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