Bluma Lesch, MD, PhD
Associate Professor of Genetics and of Obstetrics, Gynecology, and Reproductive SciencesCards
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Associate Professor of Genetics and of Obstetrics, Gynecology, and Reproductive Sciences
Biography
Bluma Lesch works on mechanisms of transcriptional regulation in the context of development, evolution, and disease, with a special interest in the genetics and epigenetics of the mammalian germ line. Her research integrates information across a wide range of biological scales, from molecular mechanism to organismal development to species evolution, using both experimental and computational approaches. Current projects focus on (1) uncovering the rules and mechanisms of gene regulatory evolution, (2) defining transgenerational epigenetic contributions to offspring phenotype, and (3) using the unique regulatory biology of the germ line to discover fundamental gene regulatory mechanisms that go awry in disease.
Dr. Lesch earned her B.S. from Yale University in 2003. She obtained her Ph.D. in 2010 from Rockefeller University and her M.D. in 2011 from Weill Cornell Medical College in New York City. She was a postdoctoral fellow at the Whitehead Institute in Cambridge, MA, from 2011-2017, where she was awarded an NIH Kirschstein postdoctoral fellowship and also named a Hope Funds for Cancer Research postdoctoral fellow. She received a Burroughs Wellcome Career Award for Medical Scientists in 2015, and returned to New Haven to join the Yale faculty in 2017. She was names a Searle Scholar in 2019 and a Pew Biomedical Scholar in 2021.
Appointments
Genetics
Associate Professor on TermPrimaryObstetrics, Gynecology & Reproductive Sciences
Associate Professor on TermSecondary
Other Departments & Organizations
- Computational Biology and Biomedical Informatics
- Genetics
- Genomics, Genetics, and Epigenetics
- Molecular Cell Biology, Genetics and Development
- Obstetrics, Gynecology & Reproductive Sciences
- Yale Cancer Center
- Yale Center for Genomic Health
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- Yale Stem Cell Center
- Yale WRHR Advisory Committee
Research
Overview
Medical Research Interests
ORCID
0000-0002-6689-0240- View Lab Website
Lab website
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Giulia Biancon, PhD
Stephanie Halene, MD, Dr Med
TuKiet Lam, PhD, BS
Gunter Wagner, PhD
Huafeng Wang
Marcello DiStasio, MD, PhD
Germ Cells
Evolution, Molecular
Chromatin Assembly and Disassembly
Publications
2024
Evolutionary innovations in germline biology of placental mammals identified by transcriptomics of first-wave spermatogenesis in opossum
Marshall K, Stadtmauer D, Maziarz J, Wagner G, Lesch B. Evolutionary innovations in germline biology of placental mammals identified by transcriptomics of first-wave spermatogenesis in opossum. Developmental Cell 2024 PMID: 39536760, DOI: 10.1016/j.devcel.2024.10.013.Peer-Reviewed Original ResearchConceptsPlacental mammalsLevel of transcriptionSingle-cell dataGene expression patternsMammalian spermatogenesisGene expression programsEpigenomic dataAdult testisEvolutionary innovationSpermatogenic cellsGene setsSpermatogenic developmentModel marsupialOpossum Monodelphis domesticaGene expressionExpression patternsGenesDevelopmental processesExpression programsSpermatogenesisMonodelphis domesticaMammalsDevelopmental timeCombination of featuresExpressionFunctional Roles of H3K4 Methylation in Transcriptional Regulation
Yu H, Lesch B. Functional Roles of H3K4 Methylation in Transcriptional Regulation. Molecular And Cellular Biology 2024, 44: 505-515. PMID: 39155435, PMCID: PMC11529435, DOI: 10.1080/10985549.2024.2388254.Peer-Reviewed Original ResearchConceptsTranscriptional regulationAssociated with active transcriptionHistone 3 lysine 4 methylationFunctional roleTranscribed lociOpen chromatinActivate transcriptionChromatin modificationsH3K4 methylationRegulatory elementsHistone methyltransferaseEpigenetic editingTranscriptional activityResidue mutationsMammalian systemsCell differentiationHistoneH3K4me1H3K4meH3K4me3ChromatinRegulationH3K4YeastLoci
2023
Human-specific epigenomic states in spermatogenesis
Liao C, Walters B, DiStasio M, Lesch B. Human-specific epigenomic states in spermatogenesis. Computational And Structural Biotechnology Journal 2023, 23: 577-588. PMID: 38274996, PMCID: PMC10809009, DOI: 10.1016/j.csbj.2023.12.037.Peer-Reviewed Original ResearchAltmetricKDM6A/UTX promotes spermatogenic gene expression across generations and is not required for male fertility†
Walters B, Rainsford S, Heuer R, Dias N, Huang X, de Rooij D, Lesch B. KDM6A/UTX promotes spermatogenic gene expression across generations and is not required for male fertility†. Biology Of Reproduction 2023, 110: 391-407. PMID: 37861693, PMCID: PMC11484508, DOI: 10.1093/biolre/ioad141.Peer-Reviewed Original ResearchCitationsConceptsMale germ lineGerm lineGenome-wide epigenetic profilingGene regulatory statesHeritable epigenetic statesHundreds of genesLoss of KDM6AEarly meiotic prophaseSpermatogenic cellsSpermatogenic gene expressionKDM6A/UTXPaternal germ lineDemethylation of H3K27me3H3K27me3 peaksH3K27me3 domainsMisregulated genesEpigenetic stateChromatin organizationRepressive modificationsTranscriptional activatorMammalian spermatogenesisChromatin undergoesLysine demethylase 6AEpigenetic profilingGene activationANALYSIS OF INTER-INDIVIDUAL VARIATION IN CHROMATIN BIVALENCY IN THE HUMAN MALE GERM LINE
Heuer R, Ayaz A, Seli E, Lesch B. ANALYSIS OF INTER-INDIVIDUAL VARIATION IN CHROMATIN BIVALENCY IN THE HUMAN MALE GERM LINE. Fertility And Sterility 2023, 120: e219-e220. DOI: 10.1016/j.fertnstert.2023.08.629.Peer-Reviewed Original ResearchDOT1L bridges transcription and heterochromatin formation at mammalian pericentromeres
Malla A, Yu H, Farris D, Kadimi S, Lam T, Cox A, Smith Z, Lesch B. DOT1L bridges transcription and heterochromatin formation at mammalian pericentromeres. EMBO Reports 2023, 24: e56492. PMID: 37317657, PMCID: PMC10398668, DOI: 10.15252/embr.202256492.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsMouse embryonic stem cellsBurst of transcriptionMajor satellite repeatsLong-term silencingRepetitive DNA elementsEmbryonic stem cellsSatellite transcriptionHeterochromatin stabilityHeterochromatin formationHeterochromatin structureChromatin stateSatellite repeatsGenome stabilityGenome integrityPericentromeric repeatsPericentromeric heterochromatinGenome featuresDNA elementsHistone H3Transcriptional activationHistone methyltransferaseRepetitive elementsDOT1L lossRepeat elementsTranscript productionDOT1L promotes spermatid differentiation by regulating expression of genes required for histone-to-protamine replacement
Malla A, Rainsford S, Smith Z, Lesch B. DOT1L promotes spermatid differentiation by regulating expression of genes required for histone-to-protamine replacement. Development 2023, 150 PMID: 37082969, PMCID: PMC10259660, DOI: 10.1242/dev.201497.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsHistone replacementMale sterilityProtamine exchangeSpermatid differentiationHistone H3 lysine 79Chromatin remodeling factorsRNA polymerase IIH3 lysine 79Expression of genesMature sperm headSperm headPostmeiotic germ cellsHistone methyltransferase DOT1LPolymerase IILysine 79Embryonic lethalityRemodeling factorsProtamine transitionProtamine replacementTranscriptional dysregulationMethyltransferase DOT1LIndispensable regulatorDOT1LHistonesGerm cells
2022
Deconvolution of in vivo protein-RNA contacts using fractionated eCLIP-seq
Biancon G, Busarello E, Joshi P, Lesch B, Halene S, Tebaldi T. Deconvolution of in vivo protein-RNA contacts using fractionated eCLIP-seq. STAR Protocols 2022, 3: 101823. PMID: 36595959, PMCID: PMC9676202, DOI: 10.1016/j.xpro.2022.101823.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsProtein-RNA interactionsIndividual RNA-binding proteinsTranscriptome-wide analysisThousands of RNAsProtein-RNA contactsRNA-binding proteinSingle nucleotide levelComputational analysis pipelineRNA processingMulticomponent complexesRNA immunoprecipitationRead countsComplete detailsAnalysis pipelineAdditional levelProteinImmunoprecipitationRNAInteractionComplexesWidespread association of the Argonaute protein AGO2 with meiotic chromatin suggests a distinct nuclear function in mammalian male reproduction
Griffin KN, Walters BW, Li H, Wang H, Biancon G, Tebaldi T, Kaya CB, Kanyo J, Lam TT, Cox AL, Halene S, Chung JJ, Lesch BJ. Widespread association of the Argonaute protein AGO2 with meiotic chromatin suggests a distinct nuclear function in mammalian male reproduction. Genome Research 2022, 32: 1655-1668. PMID: 36109149, PMCID: PMC9528986, DOI: 10.1101/gr.276578.122.Peer-Reviewed Original ResearchCitationsAltmetricConceptsMammalian male reproductionArgonaute 2Distinct nuclear functionsConditional knockoutMale reproductionProtein Argonaute 2Abnormal sperm head morphologyMeiotic chromatinAnimal developmentCytoplasmic roleNuclear functionsMale meiosisNuclear roleMRNA translationAgo2 proteinImportant genesNuclear compartmentMRNA transcriptsBiological relevanceSperm head morphologyHead morphologySpermatogenic cellsWidespread associationChromatinProtein
2021
Neuron-specific chromosomal megadomain organization is adaptive to recent retrotransposon expansions
Chandrasekaran S, Espeso-Gil S, Loh YE, Javidfar B, Kassim B, Zhu Y, Zhang Y, Dong Y, Bicks LK, Li H, Rajarajan P, Peter CJ, Sun D, Agullo-Pascual E, Iskhakova M, Estill M, Lesch BJ, Shen L, Jiang Y, Akbarian S. Neuron-specific chromosomal megadomain organization is adaptive to recent retrotransposon expansions. Nature Communications 2021, 12: 7243. PMID: 34903713, PMCID: PMC8669064, DOI: 10.1038/s41467-021-26862-z.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCellular stress response genesOpen chromatin domainsChromatin domain organizationRepeat-rich sequencesStress response genesRetrotransposon expansionsSPRET/EiJChromatin domainsChromosomal architectureChromosomal conformationDomain organizationAdult mouse cerebral cortexMurine germlineTranscriptional dysregulationResponse genesRegulatory mechanismsMus musculusMature neuronsNeuronal ablationStrong enrichmentMouse cerebral cortexSequenceSETDB1Single moleculesGermline
Academic Achievements & Community Involvement
honor Pew Scholar
National AwardPew Biomedical Scholars ProgramDetails06/15/2021United Stateshonor Searle Scholar Award
National AwardSearle Scholars ProgramDetails04/01/2019United Stateshonor Kingsley Fellow
Yale School of Medicine AwardYale School of MedicineDetails12/11/2017United Stateshonor Burroughs-Wellcome Career Award
National AwardDetails09/01/2015United Stateshonor Whitehead Institute Postdoctoral Association Education Award
Other AwardWhitehead InstituteDetails06/01/2012United States
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