David Breslow, PhD
Assistant Professor, Molecular, Cellular and Developmental BiologyCards
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Assistant Professor, Molecular, Cellular and Developmental Biology
Biography
David Breslow is an Assistant Professor in the Department of Molecular, Cellular and Developmental Biology at Yale University. David received an A.B. in Biochemical Sciences from Harvard University, working in the laboratory of Dr. Stuart Schreiber. David did his graduate work at the University of California, San Francisco in Dr. Jonathan Weissman’s lab. There he developed new high-throughput functional genomic tools for budding yeast and defined the function of Orm family proteins in sphingolipid homeostasis. As a postdoctoral fellow, David worked with Dr. Maxence Nachury at Stanford University, where he used a semi-permeabilized cell system to study protein entry into primary cilia and developed a CRISPR/Cas9-based screening platform to investigate ciliary signaling. A central focus of David’s work is been applying new systematic approaches to address fundamental questions in cell biology, with a current emphasis on the regulation and functions of the mammalian primary cilium. David joined the Yale MCDB faculty in January 2017 and his lab is located in the Yale Science Building.
Appointments
Education & Training
- Postdoctoral researcher
- Stanford University (2016)
- PhD
- University of California, San Francisco, Chemistry and Chemical Biology (2010)
- AB
- Harvard University, Biochemical Sciences (2004)
Research
Overview
Medical Subject Headings (MeSH)
ORCID
0000-0003-0245-3348- View Lab Website
Breslow lab website
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Enrique M. De La Cruz, PhD
Signal Transduction
Homeostasis
Organelle Biogenesis
Cell Cycle
High-Throughput Screening Assays
Publications
Featured Publications
Pathogenic RAB34 variants impair primary cilium assembly and cause a novel oral-facial-digital syndrome
Bruel A, Ganga A, Nosková L, Valenzuela I, Martinovic J, Duffourd Y, Zikánová M, Majer F, Kmoch S, Mohler M, Sun J, Sweeney L, Martínez-Gil N, Thauvin-Robinet C, Breslow D. Pathogenic RAB34 variants impair primary cilium assembly and cause a novel oral-facial-digital syndrome. Human Molecular Genetics 2023, 32: 2822-2831. PMID: 37384395, PMCID: PMC10481091, DOI: 10.1093/hmg/ddad109.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCilia assemblyCiliary membrane formationIntracellular ciliogenesis pathwayPrimary cilia assemblyBi-allelic missense variantsRab proteinsRab GTPaseCiliary proteinsSmall GTPaseNascent ciliaMother centriolePrimary ciliaC-terminusProtein productsPathogenic variantsRab34Cell typesFunctional impactMissense variantsGTPaseStrong lossCiliogenesisSignificant defectsGenesKey mediatorRab34 GTPase mediates ciliary membrane formation in the intracellular ciliogenesis pathway
Ganga AK, Kennedy MC, Oguchi ME, Gray S, Oliver KE, Knight TA, De La Cruz EM, Homma Y, Fukuda M, Breslow DK. Rab34 GTPase mediates ciliary membrane formation in the intracellular ciliogenesis pathway. Current Biology 2021, 31: 2895-2905.e7. PMID: 33989527, PMCID: PMC8282722, DOI: 10.1016/j.cub.2021.04.075.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsIntracellular pathwaysCiliary membrane biogenesisCiliary membrane formationIntracellular ciliogenesis pathwayMDCK cellsPolarized MDCK cellsDistinct molecular requirementsPrimary cilia formExtracellular pathwaysTissue-specific mannerCiliary pocketGTPase domainMembrane biogenesisDistinct functional propertiesCiliary vesiclesAssembly intermediatesCilia formSignal transductionGTP bindingMother centriolePrimary ciliaCiliogenesisDivergent residuesIntracellular ciliaRab34Mechanism and Regulation of Centriole and Cilium Biogenesis
Breslow DK, Holland AJ. Mechanism and Regulation of Centriole and Cilium Biogenesis. Annual Review Of Biochemistry 2019, 88: 1-34. PMID: 30601682, PMCID: PMC6588485, DOI: 10.1146/annurev-biochem-013118-111153.ChaptersCitationsAltmetricMeSH Keywords and ConceptsConceptsInterphase microtubule cytoskeletonMicrotubule-based organellesBiogenesis of centriolesMost animal cellsCore of centrosomesFormation of ciliaNine-fold symmetryCilia biologyCilia biogenesisCellular signalingMicrotubule cytoskeletonAnimal cellsMitotic spindleBasal bodiesHuman diseasesCentriolesBiogenesisRegulatory controlCentral roleCiliaExciting avenuesCentrosomesCytoskeletonOrganellesSignalingA CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies
Breslow DK, Hoogendoorn S, Kopp AR, Morgens DW, Vu BK, Kennedy MC, Han K, Li A, Hess GT, Bassik MC, Chen JK, Nachury MV. A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies. Nature Genetics 2018, 50: 460-471. PMID: 29459677, PMCID: PMC5862771, DOI: 10.1038/s41588-018-0054-7.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsFunctional genomic screensGenome-wide CRISPRCiliary functionHedgehog-responsive cellsCiliary signalingΕ-tubulinProtein complexesGenomic screenEmbryonic developmentGene disruptionPrimary ciliaΔ-tubulinNovel componentCiliopathiesCRISPRCiliary structureUnbiased toolHedgehogUnifying causeScreenGenesSignalingCiliaSystematic analysisPathwayAn in vitro assay for entry into cilia reveals unique properties of the soluble diffusion barrier
Breslow DK, Koslover EF, Seydel F, Spakowitz AJ, Nachury MV. An in vitro assay for entry into cilia reveals unique properties of the soluble diffusion barrier. Journal Of Cell Biology 2013, 203: 129-147. PMID: 24100294, PMCID: PMC3798247, DOI: 10.1083/jcb.201212024.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsActin CytoskeletonAnimalsCell LineCell MembraneCell Membrane PermeabilityCiliaDiffusionMiceMicroscopy, FluorescenceMicroscopy, VideoModels, BiologicalMolecular WeightNuclear PoreProtein TransportProteinsRecombinant Fusion ProteinsReproducibility of ResultsTime FactorsTime-Lapse ImagingTransfectionConceptsNuclear pore complexCiliary diffusion barrierPore complexActin cytoskeletonMembrane proteinsActive transportPrimary ciliaPlasma membraneCiliary membraneSpecific proteinsLarge proteinsMechanistic basisPermeabilized cellsProteinCiliaAxon initial segmentMembraneCellsCytoskeletonInitial segmentEntryTransportAssaysVivoComplexesOrm family proteins mediate sphingolipid homeostasis
Breslow DK, Collins SR, Bodenmiller B, Aebersold R, Simons K, Shevchenko A, Ejsing CS, Weissman JS. Orm family proteins mediate sphingolipid homeostasis. Nature 2010, 463: 1048-1053. PMID: 20182505, PMCID: PMC2877384, DOI: 10.1038/nature08787.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsAmino Acid SequenceAsthmaCell LineConserved SequenceFatty Acids, MonounsaturatedHeLa CellsHomeostasisHumansMolecular Sequence DataMultigene FamilyMultiprotein ComplexesPhosphoric Monoester HydrolasesPhosphorylationProtein BindingSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSerine C-PalmitoyltransferaseSphingolipidsConceptsOrm proteinsSphingolipid homeostasisSphingolipid productionFunctional genomics approachSphingolipid metabolismGenomic approachesGene familyPhosphorylation sitesORM geneORMDL genesRate-limiting enzymeRegulatory pathwaysNegative regulatorGene expressionSphingolipid synthesisSerine palmitoyltransferaseEssential roleProteinCritical mediatorGenesHomeostasisStructural componentsMetabolismMisregulationSaccharomycesA disease-associated PPP2R3C-MAP3K1 phospho-regulatory module controls centrosome function
Ganga A, Sweeney L, Rubio Ramos A, Wrinn C, Bishop C, Hamel V, Guichard P, Breslow D. A disease-associated PPP2R3C-MAP3K1 phospho-regulatory module controls centrosome function. Current Biology 2024, 34: 4824-4834.e6. PMID: 39317195, PMCID: PMC11496028, DOI: 10.1016/j.cub.2024.08.058.Peer-Reviewed Original ResearchAltmetricConceptsCentrosome functionKinase-phosphatase pairSystems genetics approachDisorders of gonadal developmentCentriolar localizationCentriole proteinsGrowth defectSystems geneticsPhosphatase subunitFunctional partnersCentrosomal proteinsGene functionMicrotubule organizationCentrosome regulationGenetic approachesPPP2R3CJNK signalingCell signalingKinase activityCentrosome biogenesisAcute overexpressionGonadal developmentRegulatory mechanismsMAP3K1Gonadal dysgenesis
2015
Chapter 11 Analysis of soluble protein entry into primary cilia using semipermeabilized cells
Breslow DK, Nachury MV. Chapter 11 Analysis of soluble protein entry into primary cilia using semipermeabilized cells. Methods In Cell Biology 2015, 127: 203-221. PMID: 25837393, PMCID: PMC4797650, DOI: 10.1016/bs.mcb.2014.12.006.BooksCitationsMeSH Keywords and ConceptsConceptsSemipermeabilized cellsProtein entriesPrimary ciliaCiliary diffusion barrierNuclear pore complexPrimary cilia functionPore complexMammalian cellsSignal transductionSpecialized compartmentsCilia functionPlasma membraneCiliary membraneIntact cellsExperimental perturbationsCell surfaceProtein exchangeCiliaVitro systemAxon initial segmentMechanistic analysisChapter 11 AnalysisUnique resourceCapture assayCells
2014
The Intraflagellar Transport Protein IFT27 Promotes BBSome Exit from Cilia through the GTPase ARL6/BBS3
Liew GM, Ye F, Nager AR, Murphy JP, Lee JS, Aguiar M, Breslow DK, Gygi SP, Nachury MV. The Intraflagellar Transport Protein IFT27 Promotes BBSome Exit from Cilia through the GTPase ARL6/BBS3. Developmental Cell 2014, 31: 265-278. PMID: 25443296, PMCID: PMC4255629, DOI: 10.1016/j.devcel.2014.09.004.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCargo entryBardet-Biedl syndrome proteinsIntraflagellar transport (IFT) machineryBiochemical reconstitution assaysNucleotide-free formCiliary exitTransport machinerySyndrome proteinGTP loadingUnbiased proteomicsCoat assemblyReconstitution assaysBBSomeARL6IFT27CiliaBBS3AssemblyProteomicsMachineryProteinCargoSortingExitActivation
2013
Sphingolipid Homeostasis in the Endoplasmic Reticulum and Beyond
Breslow DK. Sphingolipid Homeostasis in the Endoplasmic Reticulum and Beyond. Cold Spring Harbor Perspectives In Biology 2013, 5: a013326. PMID: 23545423, PMCID: PMC3683901, DOI: 10.1101/cshperspect.a013326.BooksCitationsMeSH Keywords and ConceptsConceptsSphingolipid homeostasisEndoplasmic reticulumEssential cellular rolesSphingolipid metabolismCritical regulatory sitePotent signaling moleculesCellular rolesFamily proteinsSphingolipid productionSignaling moleculesRegulatory sitesPhysiologic cuesBasic biochemistryComplex glycosphingolipidsMembrane functionHomeostasisDiverse groupSphingolipidsNew insightsReticulumMetabolic demandsDetailed understandingMetabolismStructural componentsInitial synthesis
Academic Achievements & Community Involvement
honor Maximizing Investigators' Research Award
National AwardNIH / NIGMSDetails09/01/2020United Stateshonor Excellence Award for Biomedical Research
Regional AwardSmith Family FoundationDetails12/01/2018United Stateshonor Child Health Research Award
Regional AwardCharles H. Hood FoundationDetails07/01/2018United Stateshonor Sloan Research Fellowship
National AwardAlfred P. Sloan FoundationDetails02/15/2018United Stateshonor Pathway to Independence Award (K99/R00)
National AwardNational Institutes of HealthDetails12/01/2014United States
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260 Whitney Avenue, Rm 219
New Haven, CT 06511