Tyrone DeSpenza Jr, MD, PhD
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About
Appointments
Departments & Organizations
- Kahle Lab
Education & Training
- MD
- Yale University School of Medicine (2024)
- PhD
- Yale University School of Medicine, Interdepartmental Neuroscience Program
- BA
- Dartmouth College, Neuroscience (2013)
Research
Research at a Glance
Yale Co-Authors
Frequent collaborators of Tyrone DeSpenza's published research.
Publications Timeline
A big-picture view of Tyrone DeSpenza's research output by year.
Kristopher Kahle, MD, PhD
Engin Deniz, MD
Evelyn Lake, PhD
Adriana Cherskov
Aladine Elsamadicy, MD
Duy Phan, PhD
11Publications
79Citations
Publications
2024
Pathogenic variants in autism gene KATNAL2 cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics
DeSpenza T, Singh A, Allington G, Zhao S, Lee J, Kiziltug E, Prina M, Desmet N, Dang H, Fields J, Nelson-Williams C, Zhang J, Mekbib K, Dennis E, Mehta N, Duy P, Shimelis H, Walsh L, Marlier A, Deniz E, Lake E, Constable R, Hoffman E, Lifton R, Gulledge A, Fiering S, Moreno-De-Luca A, Haider S, Alper S, Jin S, Kahle K, Luikart B. Pathogenic variants in autism gene KATNAL2 cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2314702121. PMID: 38916997, PMCID: PMC11228466, DOI: 10.1073/pnas.2314702121.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCongenital hydrocephalusCerebral ventriculomegalyPathogenic variantsPrefrontal pyramidal neuronsGenetic subsets of patientsDevelopment of ventriculomegalyRadial gliaSubsets of patientsHigh-frequency firingNeuronal connectivityHeterozygous germline variantsAutism spectrum disorderVentricular-subventricular zoneMicrotubule dynamicsImpaired spermatogenesisCSF shuntingExcitatory driveMicrotubule-severing ATPasePyramidal neuronsDisrupt neuronal connectivityGermline variantsVentriculomegalyCSF homeostasisDisrupt microtubule dynamicsPlanar cell polarity184 PTEN Mutations Portend Cerebral Ventriculomegaly With Autism-Like Deficits in Cortical Circuitry
DeSpenza T, Kizlitug E, Allington G, Barson D, O'Connor D, Robert S, Mekbib K, Singh A, Phan D, Nanda P, Mandino F, Constable T, Lake E, Carter B, Gunel M, Lifton R, Luikart B, Kahle K. 184 PTEN Mutations Portend Cerebral Ventriculomegaly With Autism-Like Deficits in Cortical Circuitry. Neurosurgery 2024, 70: 46-46. DOI: 10.1227/neu.0000000000002809_184.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingFetal ventriculomegalyCongenital hydrocephalusExome sequencingChoroid plexus hyperplasiaMutated genesCa2+ imagingMutant mouse modelsPTEN mutantsHuman fetal brainPten mutant miceSporadic CHCerebral ventriculomegalyCSF diversionObstructive hydrocephalusCH patientsCSF secretionPharmacological mTORC1 inhibitionNeurodevelopmental assessmentRadiographic biomarkersFetal brainPTEN mutationsAqueductal stenosisPTEN deletionVentriculomegaly
2023
A novel SMARCC1 BAFopathy implicates neural progenitor epigenetic dysregulation in human hydrocephalus
Singh A, Allington G, Viviano S, McGee S, Kiziltug E, Ma S, Zhao S, Mekbib K, Shohfi J, Duy P, DeSpenza T, Furey C, Reeves B, Smith H, Sousa A, Cherskov A, Allocco A, Nelson-Williams C, Haider S, Rizvi S, Alper S, Sestan N, Shimelis H, Walsh L, Lifton R, Moreno-De-Luca A, Jin S, Kruszka P, Deniz E, Kahle K. A novel SMARCC1 BAFopathy implicates neural progenitor epigenetic dysregulation in human hydrocephalus. Brain 2023, 147: 1553-1570. PMID: 38128548, PMCID: PMC10994532, DOI: 10.1093/brain/awad405.Peer-Reviewed Original ResearchCitationsAltmetricConceptsAqueductal stenosisDe novo variantsCardiac defectsCerebral ventriculomegalyPatient cohortFetal brain transcriptomeStructural brain disordersTranscription factor NeuroD2Large patient cohortCorpus callosum abnormalitiesHuman fetal brainOptical coherence tomographyWhole-exome sequencingNeural stem cellsCH patientsHuman hydrocephalusControl cohortClinical managementCommon disorderCallosum abnormalitiesFetal brainBrain disordersBrain surgeryCH pathogenesisPatientsMutation of key signaling regulators of cerebrovascular development in vein of Galen malformations
Zhao S, Mekbib K, van der Ent M, Allington G, Prendergast A, Chau J, Smith H, Shohfi J, Ocken J, Duran D, Furey C, Hao L, Duy P, Reeves B, Zhang J, Nelson-Williams C, Chen D, Li B, Nottoli T, Bai S, Rolle M, Zeng X, Dong W, Fu P, Wang Y, Mane S, Piwowarczyk P, Fehnel K, See A, Iskandar B, Aagaard-Kienitz B, Moyer Q, Dennis E, Kiziltug E, Kundishora A, DeSpenza T, Greenberg A, Kidanemariam S, Hale A, Johnston J, Jackson E, Storm P, Lang S, Butler W, Carter B, Chapman P, Stapleton C, Patel A, Rodesch G, Smajda S, Berenstein A, Barak T, Erson-Omay E, Zhao H, Moreno-De-Luca A, Proctor M, Smith E, Orbach D, Alper S, Nicoli S, Boggon T, Lifton R, Gunel M, King P, Jin S, Kahle K. Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations. Nature Communications 2023, 14: 7452. PMID: 37978175, PMCID: PMC10656524, DOI: 10.1038/s41467-023-43062-z.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsEphrin receptor B4Galen malformationBrain arteriovenous malformationsP120 RasGAPTransmitted variantsArteriovenous malformationsDe novo variantsSingle-cell transcriptomesSignificant burdenCerebrovascular developmentIntegrative genomic analysisEndothelial cellsVenous networkAdditional probandsMalformationsNovo variantsMissense variantsGenomic analysisDevelopmental angiogenesisVascular developmentDamaging variantsVeinRasGAPIntegrated analysisPatientsHuman genetics and molecular genomics of Chiari malformation type 1
Mekbib K, Muñoz W, Allington G, McGee S, Mehta N, Shofi J, Fortes C, Le H, Nelson-Williams C, Nanda P, Dennis E, Kundishora A, Khanna A, Smith H, Ocken J, Greenberg A, Wu R, Moreno-De-Luca A, DeSpenza T, Zhao S, Marlier A, Jin S, Alper S, Butler W, Kahle K. Human genetics and molecular genomics of Chiari malformation type 1. Trends In Molecular Medicine 2023, 29: 1059-1075. PMID: 37802664, DOI: 10.1016/j.molmed.2023.08.013.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsWhole-exome sequencingChiari malformation type 1Recent whole-exome sequencingDevelopmental signalingTranscription regulationCandidate genesGenetic studiesMolecular genomicsHuman geneticsSignificant genetic contributionGenetic contributionType 1De novo germlineExome sequencingStructural brain disordersTreatment failureSurgical approachSpinal canalCerebellar tonsilsCraniocervical junctionCaudal displacementBrain disordersNeurophysiological endophenotypesGenomicsGermlineThe choroid plexus links innate immunity to CSF dysregulation in hydrocephalus
Robert S, Reeves B, Kiziltug E, Duy P, Karimy J, Mansuri M, Marlier A, Allington G, Greenberg A, DeSpenza T, Singh A, Zeng X, Mekbib K, Kundishora A, Nelson-Williams C, Hao L, Zhang J, Lam T, Wilson R, Butler W, Diluna M, Feinberg P, Schafer D, Movahedi K, Tannenbaum A, Koundal S, Chen X, Benveniste H, Limbrick D, Schiff S, Carter B, Gunel M, Simard J, Lifton R, Alper S, Delpire E, Kahle K. The choroid plexus links innate immunity to CSF dysregulation in hydrocephalus. Cell 2023, 186: 764-785.e21. PMID: 36803604, PMCID: PMC10069664, DOI: 10.1016/j.cell.2023.01.017.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPost-infectious hydrocephalusTLR4-dependent immune responseBlood-cerebrospinal fluid barrierSmall molecule pharmacotherapyCell cross talkPharmacological immunomodulationCytokine stormNeuroimmune disordersBrain infectionDrug treatmentImmune responseAcquired hydrocephalusHydrocephalus modelChoroid plexusFluid barrierHydrocephalusEpithelial cellsCSFMulti-omics investigationsCross talkHypersecretionHemorrhagePharmacotherapyImmunomodulationPlexus
2022
374 Multi-omic Analysis Identifies a SPAK Kinase-regulated Ensemble of Choroid Plexus Ion Transport Proteins Relevant for Post-infectious Hydrocephalus
Robert S, Reeves B, Karimy J, Marlier A, Kiziltug E, DeSpenza T, Singh A, Allington G, Phan D, Zhang J, Kahle K. 374 Multi-omic Analysis Identifies a SPAK Kinase-regulated Ensemble of Choroid Plexus Ion Transport Proteins Relevant for Post-infectious Hydrocephalus. Neurosurgery 2022, 68: 89-89. DOI: 10.1227/neu.0000000000001880_374.Peer-Reviewed Original Research
2021
PTEN mutations in autism spectrum disorder and congenital hydrocephalus: developmental pleiotropy and therapeutic targets
DeSpenza T, Carlson M, Panchagnula S, Robert S, Duy PQ, Mermin-Bunnell N, Reeves BC, Kundishora A, Elsamadicy AA, Smith H, Ocken J, Alper SL, Jin SC, Hoffman EJ, Kahle KT. PTEN mutations in autism spectrum disorder and congenital hydrocephalus: developmental pleiotropy and therapeutic targets. Trends In Neurosciences 2021, 44: 961-976. PMID: 34625286, PMCID: PMC8692171, DOI: 10.1016/j.tins.2021.08.007.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsDevelopmental pleiotropyPTEN-PI3KMTOR pathwayMolecular pathophysiologyPTEN mutationsMolecular similarityTherapeutic targetCommon underlying mechanismNeurodevelopmental disordersUnderlying mechanismTherapeutic promisePleiotropyBiologyPhenotypicMutationsLimited understandingPathwayCommon neurodevelopmental disorderAutism spectrum disorderSimilarityTarget
2020
Integrative Genomics Implicates Genetic Disruption of Prenatal Neurogenesis in Congenital Hydrocephalus
Panchagnula S, Jin S, Dong W, Kundishora A, Moreno-De-Luca A, Furey C, Allocco A, Walker R, Nelson-Williams C, Smith H, Dunbar A, Conine S, Lu Q, Zen X, Sierant M, Knight J, Sullivan W, Phan D, DeSpenza T, Reeves B, Karimy J, Marlier A, Castaldi C, Tikhonova I, Li B, Peña; H, Broach J, Kabachelor E, Ssenyonga P, Hehnly C, Ge L, Keren B, Timberlake A, Goto J, Mangano F, Johnston J, Butler W, Warf B, Smith E, Schiff S, Limbrick D, Heuer G, Jackson E, Iskandar B, Mane S, Haider S, Guclu B, Bayri Y, Sahin Y, Duncan C, Apuzzo M, DiLuna M, Hoffman E, Sestan N, Ment L, Alper S, Bilguvar K, Geschwind D, Günel M, Lifton R, Kahle K. Integrative Genomics Implicates Genetic Disruption of Prenatal Neurogenesis in Congenital Hydrocephalus. Neurosurgery 2020, 67 DOI: 10.1093/neuros/nyaa447_572.Peer-Reviewed Original ResearchTRIM71 Mutations Cause Human and Murine Congenital Hydrocephalus by Impairing Prenatal Neural Stem Cell Regulation
Phan D, Jin S, Weise S, Marini C, Dong W, Kundishora A, Torres-Fernandez L, Cuevas E, Hao L, Furey C, Zeng X, Jux B, Sousa A, Liu F, Kim S, Li M, Yang Y, Takeo Y, Foster D, Nelson-Williams C, Allocco A, Smith H, Dunbar A, Sullivan W, Ha Y, Selvaganesan K, Sheth A, DeSpenza T, Reeves B, Goto J, Marlier A, Warf B, Moreno-De-Luca A, Lake E, Constable T, Sestan N, Lin H, Alper S, Slack F, Wulczyn F, Kolanus W, Lifton R, Kahle K. TRIM71 Mutations Cause Human and Murine Congenital Hydrocephalus by Impairing Prenatal Neural Stem Cell Regulation. Neurosurgery 2020, 67 DOI: 10.1093/neuros/nyaa447_576.Peer-Reviewed Original Research