Jun Lu, PhD
Cards
Appointments
Contact Info
About
Titles
Associate Professor of Genetics
Appointments
Genetics
Associate Professor TenurePrimary
Other Departments & Organizations
- Center for Biomedical Data Science
- Center for RNA Science and Medicine
- Computational Biology and Biomedical Informatics
- Diabetes Research Center
- Genetics
- Genomics, Genetics, and Epigenetics
- Lu Lab
- Molecular Cell Biology, Genetics and Development
- Yale Cancer Center
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- Yale Stem Cell Center
- Yale Ventures
- YCCEH
Education & Training
- Postdoc Associate
- Broad Institute or MIT and Harvard (2008)
- PhD
- Boston University (2003)
Research
Overview
The completion of the human genome project leads to the realization that only a small percentage of our heritable DNA sequences encodes proteins. Instead of being “junk DNA”, a significant portion of the noncoding genome has functions, in the forms of non-coding RNAs, binding sites for protein factors or other functional sequences. These noncoding elements often cross-talk with epigenetic machinery to regulate cell fate and behavior.
In our laboratory, we use the amazing blood-forming system, or hematopoiesis, as a model to study the noncoding and epigenetic controls. In a normal adult human being, ~100 to 200 billion new blood cells are generated every day to replace similar numbers of existing blood cells. These mature blood cells originate from hematopoietic stem cells and exhibit vastly different forms, shapes and functions, regulating processes such as innate and adaptive immune responses, oxygen transport and coagulation. Mature blood cells, such as macrophages and neutrophils, can also be found in tumor tissues to control tumor cell behavior and anti-cancer immune responses. During aging, hematopoietic stem cells accumulate mutations in key tumor suppressor genes, most frequently those regulating DNA methylation. Mutant hematopoietic stem cells out-compete normal stem cells in a process termed clonal hematopoiesis. Clonal hematopoiesis is a near universal feature of human aging, increases the risk of diseases such as leukemia, and can have wider impacts on other aging-associated diseases such as vascular defects and solid cancer.
The fascinating biology discussed above raises a number of intriguing questions that we are addressing in our lab. What regulates the cross-talk between cancer cells and hematopoietic cells? What regulates the competition between clones of hematopoietic stem cells? What regulates the transformation of normal hematopoietic stem cell into malignant cells? How is the speed of hematopoietic regeneration regulated? What controls the form and function of mature blood cells?
Medical Subject Headings (MeSH)
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Shangqin Guo, PhD
Sajid A Khan, MD, FACS, FSSO
Diane Krause, MD, PhD
Mei Zhong, PhD
Caihong Qiu, PhD
Dianqing (Dan) Wu, PhD
Cell Differentiation
Cell Lineage
Hematopoiesis
Neoplasms
Publications
Featured Publications
Evitar: designing anti-viral RNA therapies against future RNA viruses
Zhang D, Tian J, Wang Y, Lu J. Evitar: designing anti-viral RNA therapies against future RNA viruses. Bioinformatics 2022, 38: 2437-2443. PMID: 35294970, PMCID: PMC9048652, DOI: 10.1093/bioinformatics/btac144.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsCoronavirus disease 2019 (COVID-19) pandemicSwine flu virusRNA virusesDisease 2019 pandemicRNA virus outbreaksMERS-CoV virusesPre-designed siRNAsShelf therapeuticsRespiratory virusesFlu virusVirusVirus outbreakNew RNA virusRNA therapyLack of availabilityTherapeuticsViral sequencesRNA therapeuticsSiRNAs5‐Fluorouracil efficacy requires anti‐tumor immunity triggered by cancer‐cell‐intrinsic STING
Tian J, Zhang D, Kurbatov V, Wang Q, Wang Y, Fang D, Wu L, Bosenberg M, Muzumdar MD, Khan S, Lu Q, Yan Q, Lu J. 5‐Fluorouracil efficacy requires anti‐tumor immunity triggered by cancer‐cell‐intrinsic STING. The EMBO Journal 2021, 40: e106065. PMID: 33615517, PMCID: PMC8013832, DOI: 10.15252/embj.2020106065.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsAnti-tumor immunityTumor burdenSubsequent type I interferon productionHigh STING expressionIntratumoral T cellsT-cell depletionType I interferon productionI interferon productionLoss of STINGImmunocompetent hostsColorectal specimensT cellsSTING expressionBetter survivalHigh doseTherapeutic effectivenessHuman colorectal specimensMelanoma tumorsInterferon productionChemotherapeutic drugsMurine colonImmunityEfficacyStingsColonSingle-cell microRNA-mRNA co-sequencing reveals non-genetic heterogeneity and mechanisms of microRNA regulation
Wang N, Zheng J, Chen Z, Liu Y, Dura B, Kwak M, Xavier-Ferrucio J, Lu YC, Zhang M, Roden C, Cheng J, Krause DS, Ding Y, Fan R, Lu J. Single-cell microRNA-mRNA co-sequencing reveals non-genetic heterogeneity and mechanisms of microRNA regulation. Nature Communications 2019, 10: 95. PMID: 30626865, PMCID: PMC6327095, DOI: 10.1038/s41467-018-07981-6.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsSame single cellMicroRNA-mRNASingle cellsGenome-scale analysisNon-genetic cellNon-genetic heterogeneityMultiple omic profilesGenomic approachesMicroRNA regulationMolecular regulationTarget mRNAsExpression variabilityCellular pathwaysRegulatory relationshipsLevels of microRNAsIntercellular heterogeneityOmics profilesIntercellular variabilityCell heterogeneityMRNA profilesMicroRNAsMRNACellsRegulationExpressionThe DNA Methylcytosine Dioxygenase Tet2 Sustains Immunosuppressive Function of Tumor-Infiltrating Myeloid Cells to Promote Melanoma Progression
Pan W, Zhu S, Qu K, Meeth K, Cheng J, He K, Ma H, Liao Y, Wen X, Roden C, Tobiasova Z, Wei Z, Zhao J, Liu J, Zheng J, Guo B, Khan SA, Bosenberg M, Flavell RA, Lu J. The DNA Methylcytosine Dioxygenase Tet2 Sustains Immunosuppressive Function of Tumor-Infiltrating Myeloid Cells to Promote Melanoma Progression. Immunity 2017, 47: 284-297.e5. PMID: 28813659, PMCID: PMC5710009, DOI: 10.1016/j.immuni.2017.07.020.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsImmunosuppressive functionMyeloid cellsIntratumoral myeloid cellsNon-hematologic malignanciesMyeloid-specific deletionTumor-associated macrophagesReduced tumor growthTumor-promoting functionsProinflammatory onesMyD88 pathwayMelanoma patientsCell depletionEffector TRole of TET2Methylcytosine dioxygenase TET2Mouse modelIL-1RMelanoma growthTherapeutic targetTumor growthTET2 expressionMelanoma progressionHematopoietic malignanciesMalignancyTET2Novel determinants of mammalian primary microRNA processing revealed by systematic evaluation of hairpin-containing transcripts and human genetic variation
Roden C, Gaillard J, Kanoria S, Rennie W, Barish S, Cheng J, Pan W, Liu J, Cotsapas C, Ding Y, Lu J. Novel determinants of mammalian primary microRNA processing revealed by systematic evaluation of hairpin-containing transcripts and human genetic variation. Genome Research 2017, 27: 374-384. PMID: 28087842, PMCID: PMC5340965, DOI: 10.1101/gr.208900.116.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPri-miRNA processingHuman genetic variationGenetic variationPrimary sequence motifsPrimary microRNA processingMiRNA biogenesisDisease-causing mutationsPrimary miRNAsPri-miRNAsSequence motifsMiRNA hairpinsMicroRNA processingMature microRNAsSequence featuresRNA hairpinsComputational pipelineNovel determinantStem lengthUnpaired basesHairpinTranscriptsStemBiogenesisGenomeMiRNAs
2024
PD-1H/VISTA mediates immune evasion in acute myeloid leukemia
Kim T, Han X, Hu Q, Vandsemb E, Fielder C, Hong J, Kim K, Mason E, Plowman R, Wang J, Wang Q, Zhang J, Badri T, Sanmamed M, Zheng L, Zhang T, Alawa J, Lee S, Zeidan A, Halene S, Pillai M, Chandhok N, Lu J, Xu M, Gore S, Chen L. PD-1H/VISTA mediates immune evasion in acute myeloid leukemia. Journal Of Clinical Investigation 2024, 134 PMID: 38060328, PMCID: PMC10836799, DOI: 10.1172/jci164325.Peer-Reviewed Original ResearchAltmetricCell surface RNAs control neutrophil recruitment
Zhang N, Tang W, Torres L, Wang X, Ajaj Y, Zhu L, Luan Y, Zhou H, Wang Y, Zhang D, Kurbatov V, Khan S, Kumar P, Hidalgo A, Wu D, Lu J. Cell surface RNAs control neutrophil recruitment. Cell 2024, 187: 846-860.e17. PMID: 38262409, PMCID: PMC10922858, DOI: 10.1016/j.cell.2023.12.033.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCell surfaceMammalian homologOuter cell surfaceRNA transportGlycan modificationsMammalian cellsSID-1Cellular functionsRecruitment to inflammatory sitesGlycoRNARNAMurine neutrophilsFunctional significanceNeutrophil recruitmentNeutrophil recruitment to inflammatory sitesBiological importanceCellsNeutrophil adhesionReduced neutrophil adhesionHomologyGlycansGenesInflammatory sitesRecruitmentEndothelial cells
2023
Ten-Eleven-Translocation Genes in Cancer
Wang Y, Wang X, Lu J. Ten-Eleven-Translocation Genes in Cancer. Cancer Treatment And Research 2023, 190: 363-373. PMID: 38113007, DOI: 10.1007/978-3-031-45654-1_11.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsTET mutationsTen-ElevenBiochemical functionsTranslocation (TET) familyTranslocation geneHematopoietic malignanciesHematopoietic expansionGenesHuman cancersMutationsCritical roleImmune responseTET2Clonal hematopoiesisSolid cancersEpigenomeTET1TET3RNABiologyUnanswered questionsDNAHematopoiesisCooperateTETsCell Surface RNAs Control Neutrophil Function
Zhang N, Tang W, Torres L, Zhu L, Wang X, Ajaj Y, Wang Y, Zhang D, Kurbatov V, Zhou H, Luan Y, Kumar P, Hidalgo A, Wu D, Lu J. Cell Surface RNAs Control Neutrophil Function. Blood 2023, 142: 674. DOI: 10.1182/blood-2023-187570.Peer-Reviewed Original ResearchConceptsExtracellular RNaseCell surfaceTotal RNABona fide ligandsEndothelial cellsOuter cell surfaceTransendothelial migrationMammalian cellsSuch RNAsGlycan modificationsCellular RNAGlycoRNARNase digestionLive cellsRNAHematopoietic cellsRNase treatmentSimilar defectsIntegrin levelsConfocal microscopyRNaseGlycan fractionImportant functionsHomologuesRecombinant E-selectin
2022
Bile acid distributions, sex-specificity, and prognosis in colorectal cancer
Cai Y, Shen X, Lu L, Yan H, Huang H, Gaule P, Muca E, Theriot CM, Rattray Z, Rattray NJW, Lu J, Ahuja N, Zhang Y, Paty PB, Khan SA, Johnson CH. Bile acid distributions, sex-specificity, and prognosis in colorectal cancer. Biology Of Sex Differences 2022, 13: 61. PMID: 36274154, PMCID: PMC9590160, DOI: 10.1186/s13293-022-00473-9.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsLeft-sided colon tumorsRight-sided colon tumorsColon cancer patientsColorectal cancerTumor locationBile acidsColon tumorsCancer patientsQuantitative immunofluorescencePrimary tumor locationImmune regulatory cellsRecurrence-free survivalBile acid metabolismSecondary bile acidsBile acid distributionBile acid analysisBackgroundBile acidsOverall survivalRegulatory cellsCRC patientsMale patientsPatient sexImmune cellsPatient prognosisImmune response
Academic Achievements and Community Involvement
honor Stewart Trust Fellow
National AwardThe Alexander & Margaret Stewart TrustDetails07/01/2012United Stateshonor Forbeck Scholar
National AwardWilliam Guy Forbeck FoundationDetails01/01/2007United States
Links & Media
News
- February 28, 2024
YCC Research Publications
- January 22, 2024Source: YaleNews
RNAs Do Work Outside of Cells, Too
- October 06, 2023Source: Yale Daily News
Local high school’s BioScience Club introduces students to careers in science
- September 19, 2023
Colon Tumor Location Matters for Metastatic Disease, According to Study
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Everyone Ryan Flynn, MD,PhD