Dianqing (Dan) Wu, PhD
Gladys Phillips Crofoot Professor of PharmacologyDownloadHi-Res Photo
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Appointments
Pharmacology
Primary
Contact Info
Pharmacology
PO Box 208089, 10 Amistad
New Haven, CT 06520-8089
United States
About
Titles
Gladys Phillips Crofoot Professor of Pharmacology
Appointments
Pharmacology
ProfessorPrimary
Other Departments & Organizations
- Cancer Signaling Networks
- Fellowship Training
- Molecular Medicine, Pharmacology, and Physiology
- Pharmacology
- Primary Faculty
- Vascular Biology and Therapeutics Program
- Yale Cancer Center
- Yale Center for Immuno-Oncology
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- Yale Stem Cell Center
- Yale Ventures
- YCCEH
Education & Training
- Postdoc
- California Institute of Technology (1994)
- PhD
- Clarkson University (1991)
- BS
- Nanjing University (1985)
Research
Overview
Our long-term goal is to understand the molecular basis and function of signal transduction pathways, with the emphasis on those initiated by seven-transmembrane receptors. These receptors can be divided into two groups: one couples to heterotrimeric GTP-binding proteins; and the other binds to ligands including hedgehog proteins and Wnt proteins. Currently, we are focusing on chemoattractant and Wnt-activated signaling.
Chemoattractants, including the superfamily of chemotactic cytokines, chemokines, play an important role in host defense by attracting and activating leukocytes at sites of injury and infection. However, their unchecked activities contribute to may inflammation-related diseases, including atherosclerosis, arthritis, tumorigenesis, and various allergies. Work in my lab has made significant contributions to the understanding of signaling mechanisms and functions of a number of chemoattractant-activated pathways. These include pathways linked by PLC ß, PI3K?, PIXa/Pak/Cdc42, PTEN, P-Rex1, and Myo1f. We are continuing to use a combination of molecular and cell biological, biochemical, transgenic, functional genomic, and proteomic approaches to characterize novel chemoattractant signaling mechanisms and study their functions in cell migration and inflammation-related paradigms.
The Wnt family of secretory glycoproteins participates in a wide variety of developmental events including, control of cell growth, generation of cell polarity, and specification of cell fate. Wnt pathways have been also closely linked to tumorigenesis and bone formation. Most notable contributions from my is the discovery of the interaction between Wnt coreceptor LRP-5 and Axin, which provides the first connection from a Wnt receptor to a intracellular signaling component and the characterization of the role of Dkk2 in regulation of osteogenic differentiation. We are continuing to work on the elucidation of fundamental mechanisms of Wnt signaling and characterization of their role in pathophysiological processes, including osteoporosis, metabolic syndrome, diabetes, and tumorigenesis, using computation-based virtual screening and chemical genomic approaches, in addition to the aforementioned ones.1) Wnt signaling mechanisms and functions
2) Regulation of neutrophil migration
3) Atherosclerosis
4) Wnt signaling in bone development and diseases
5) Wnt signaling and stem cell biology
2) Regulation of neutrophil migration
3) Atherosclerosis
4) Wnt signaling in bone development and diseases
5) Wnt signaling and stem cell biology
Medical Subject Headings (MeSH)
Chemicals and Drugs; Chemotaxis; GTP-Binding Proteins; Inflammation; Pharmacology; Signal Transduction; Stem Cells
Research at a Glance
Yale Co-Authors
Frequent collaborators of Dianqing (Dan) Wu's published research.
Publications Timeline
A big-picture view of Dianqing (Dan) Wu's research output by year.
Research Interests
Research topics Dianqing (Dan) Wu is interested in exploring.
Wenwen Tang, PhD
Barani Kumar Rajendran
Jesse Rinehart, PhD
Jun Lu, PhD
Priti Kumar, PhD
Yansheng Liu, PhD
61Publications
7,092Citations
Signal Transduction
GTP-Binding Proteins
Chemotaxis
Publications
2024
LDL receptor-related protein 5 selectively transports unesterified polyunsaturated fatty acids to intracellular compartments
Tang W, Luan Y, Yuan Q, Li A, Chen S, Menacherry S, Young L, Wu D. LDL receptor-related protein 5 selectively transports unesterified polyunsaturated fatty acids to intracellular compartments. Nature Communications 2024, 15: 3068. PMID: 38594269, PMCID: PMC11004178, DOI: 10.1038/s41467-024-47262-z.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsConceptsLDL receptor-related protein 5Intracellular compartmentsPolyunsaturated fatty acidsProtein 5Ligand-binding repeatsBiologically important mechanismsAssociated with human healthImport mechanismExtracellular trap formationInhibit mTORC1Cell typesFatty acidsTrap formationN-3 polyunsaturated fatty acidsCompartmentProtect miceLDLAMyocardial injuryHomologyIschemia-reperfusionMTORC1LysosomesLRP6Human healthFATP2Wnt5 controls splenic myelopoiesis and neutrophil functional ambivalency during DSS-induced colitis
Luan Y, Hu J, Wang Q, Wang X, Li W, Qu R, Yang C, Rajendran B, Zhou H, Liu P, Zhang N, Shi Y, Liu Y, Tang W, Lu J, Wu D. Wnt5 controls splenic myelopoiesis and neutrophil functional ambivalency during DSS-induced colitis. Cell Reports 2024, 43: 113934. PMID: 38461416, PMCID: PMC11064424, DOI: 10.1016/j.celrep.2024.113934.Peer-Reviewed Original ResearchAltmetricConceptsCD8<sup>+</sup> T cell activationNeutrophil productionNeutrophil plasticitySplenic extramedullary myelopoiesisFamily member 5T cell activationInnate immune cellsSplenic stromal cellsDSS-induced colitisAnti-inflammatory protectionCD101 expressionPro-inflammatory activitySplenic myelopoiesisExtramedullary myelopoiesisBone marrowImmune cellsSplenic neutrophilsMember 5Autoimmune diseasesInflammatory outcomesCell activationStromal cellsColitisSplenic productionElevated numbersCell 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 cellsThe CUL5 E3 ligase complex negatively regulates central signaling pathways in CD8+ T cells
Liao X, Li W, Zhou H, Rajendran B, Li A, Ren J, Luan Y, Calderwood D, Turk B, Tang W, Liu Y, Wu D. The CUL5 E3 ligase complex negatively regulates central signaling pathways in CD8+ T cells. Nature Communications 2024, 15: 603. PMID: 38242867, PMCID: PMC10798966, DOI: 10.1038/s41467-024-44885-0.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCD8+ T cellsT cellsCancer immunotherapyMouse CD8+ T cellsAnti-tumor immunityTumor growth inhibition abilityAnti-tumor effectsInhibition of neddylationCD8Effector functionsTCR stimulationIL2 signalingCentral signaling pathwaysCore signaling pathwaysEffector activityNegative regulatory mechanismsTranslational implicationsImmunotherapyGrowth inhibition abilityCytokine signalingTCRProteomic alterationsSignaling pathwayCancerCRISPR-based screens
2023
Cell 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-selectinLithium ameliorates Niemann-Pick C1 disease phenotypes by impeding STING/SREBP2 activation
Han S, Wang Q, Song Y, Pang M, Ren C, Wang J, Guan D, Xu W, Li F, Wang F, Zhou X, Fernández-Hernando C, Zhang H, Wu D, Ye Z. Lithium ameliorates Niemann-Pick C1 disease phenotypes by impeding STING/SREBP2 activation. IScience 2023, 26: 106613. PMID: 37128603, PMCID: PMC10148154, DOI: 10.1016/j.isci.2023.106613.Peer-Reviewed Original ResearchAltmetricConceptsTherapeutic optionsSTING activationPotential therapeutic optionProgressive neurodegenerative phenotypeNiemann-Pick disease type CGenetic lysosomal disorderNP-C patientsCytosolic calcium concentrationDisease type CEffects of lithiumCerebellar inflammationLithium treatmentMouse modelLithium effectsLysosomal disordersNeurodegenerative phenotypeCalcium concentrationSREBP2 activationDisease phenotypeType CMiceSREBP2 pathwayActivationDeficient fibroblastsPhenotype
2021
Dickkopf-2 regulates the stem cell marker LGR5 in colorectal cancer via HNF4α1
Shin JH, Jeong J, Choi J, Lim J, Dinesh RK, Braverman J, Hong JY, Maher SE, Vesely M, Kim W, Koo JH, Tang W, Wu D, Blackburn HN, Xicola RM, Llor X, Yilmaz O, Choi JM, Bothwell ALM. Dickkopf-2 regulates the stem cell marker LGR5 in colorectal cancer via HNF4α1. IScience 2021, 24: 102411. PMID: 33997693, PMCID: PMC8099562, DOI: 10.1016/j.isci.2021.102411.Peer-Reviewed Original ResearchCitationsAltmetricConceptsColorectal cancerDickkopf-2Colitis-associated cancerColorectal cancer stemnessStem cell marker Lgr5Colonic epithelial cellsAggressive progressionCancer stemnessLGR5 expressionColonic organoidsCancerEpithelial cellsCell marker genesStem cell marker genesSignificant increaseGenetic depletionWnt ligandsStem cellsProgressionLgr5StemnessCellsExpressionSequential mutationsMutationsIn vivo self-assembled small RNAs as a new generation of RNAi therapeutics
Fu Z, Zhang X, Zhou X, Ur-Rehman U, Yu M, Liang H, Guo H, Guo X, Kong Y, Su Y, Ye Y, Hu X, Cheng W, Wu J, Wang Y, Gu Y, Lu S, Wu D, Zen K, Li J, Yan C, Zhang C, Chen X. In vivo self-assembled small RNAs as a new generation of RNAi therapeutics. Cell Research 2021, 31: 631-648. PMID: 33782530, PMCID: PMC8169669, DOI: 10.1038/s41422-021-00491-z.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsRNAi therapeuticsRNAi therapyVivo siRNA deliveryEGFR/KRASSiRNA deliveryVivo deliverySynthetic siRNAsLung cancerHost liverPotent target geneSecretory exosomesTherapeutic valueCircuit moduleArtificial vehiclesGenetic circuitsTherapyMultiple tissuesSiRNAsCritical targetPrinciple strategyTissueSpecific tissuesTherapeuticsDeliveryExosomes
2013
PI3Kγ inhibition alleviates symptoms and increases axon number in experimental autoimmune encephalomyelitis mice
Li H, Park D, Abdul-Muneer P, Xu B, Wang H, Xing B, Wu D, Li S. PI3Kγ inhibition alleviates symptoms and increases axon number in experimental autoimmune encephalomyelitis mice. Neuroscience 2013, 253: 89-99. PMID: 24012746, PMCID: PMC9529370, DOI: 10.1016/j.neuroscience.2013.08.051.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsAnimalsAxonsCD3 ComplexClass Ib Phosphatidylinositol 3-KinaseDioxolesDisease Models, AnimalEctodysplasinsEncephalomyelitis, Autoimmune, ExperimentalEnzyme InhibitorsGene Expression RegulationMiceMice, Inbred C57BLMice, KnockoutMyelin SheathMyelin-Oligodendrocyte GlycoproteinNeurofilament ProteinsPeptide FragmentsPhosphoinositide-3 Kinase InhibitorsSerotoninSeverity of Illness IndexSpinal CordThiazolidinedionesTime FactorsConceptsExperimental autoimmune encephalomyelitisMultiple sclerosisEAE miceSpinal cordExperimental autoimmune encephalomyelitis (EAE) miceAutoimmune CNS inflammationLumbar spinal cordNumber of axonsCNS inflammationAutoimmune encephalomyelitisSystemic treatmentClinical symptomsPI3Kγ inhibitionInflammatory cellsAxon numberClinical signsInflammatory responseInflammatory reactionKnockout miceFiber tractsMicePI3Kγ inhibitorsCordSymptomsPI3KγGenetic deletion of catalytic subunits of AMP-activated protein kinase increases osteoclasts and reduces bone mass in young adult mice.
Kang H, Viollet B, Wu D. Genetic deletion of catalytic subunits of AMP-activated protein kinase increases osteoclasts and reduces bone mass in young adult mice. Journal Of Biological Chemistry 2013, 288: 23432. PMCID: PMC3743511, DOI: 10.1074/jbc.a112.430389.Peer-Reviewed Original ResearchCitations
Links & Media
Media
- A polarized mouse neutrophil
News
- January 22, 2024Source: YaleNews
RNAs Do Work Outside of Cells, Too
- June 27, 2018
A new colorectal cancer discovery
- June 22, 2018
Nine Faculty Members Appointed to Endowed Positions
- February 11, 2018
Researchers develop novel immunotherapy to target colorectal cancer
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Pharmacology
PO Box 208089, 10 Amistad
New Haven, CT 06520-8089
United States